Efficacy and safety of immune checkpoint inhibitors for hepatocellular carcinoma patients with macrovascular invasion or extrahepatic spread: a systematic review and meta-analysis of 54 studies with 6187 hepatocellular carcinoma patients.

BACKGROUND AND AIMS: The impacts of macrovascular invasion (MVI) or extrahepatic spread (EHS) on the efficacy and safety of immune checkpoint inhibitors (ICIs) among hepatocellular carcinoma (HCC) patients remain unclear. Thus, we conducted a systematic review and meta-analysis to clarify whether ICI therapy is a feasible treatment option for HCC with MVI or EHS. METHODS: Eligible studies published before September 14, 2022, were retrieved. In this meta-analysis, the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of adverse events (AEs) were outcomes of interest. RESULTS: Fifty-four studies involving 6187 individuals were included. The findings indicated that the presence of EHS in ICI-treated HCC patients may indicate an inferior ORR (OR 0.77, 95% CI 0.63-0.96), but may not significantly affect the PFS (multivariate analyses: HR 1.27, 95% CI 0.70-2.31) and OS (multivariate analyses: HR 1.23, 95% CI 0.70-2.16). Additionally, the presence of MVI in ICI-treated HCC patients may not have significant prognostic impact on ORR (OR 0.84, 95% CI 0.64-1.10), but may indicate inferior PFS (multivariate analyses: HR 1.75, 95% CI 1.07-2.84) and OS (multivariate analyses: HR 2.03, 95% CI 1.31-3.14). The presence of EHS or MVI in ICI-treated HCC patients may not significantly impact the occurrence of any serious immune-related adverse events (irAEs) (grades ≥ 3) (EHS: OR 0.44, 95% CI 0.12-1.56; MVI: OR 0.68, 95% CI 0.24-1.88). CONCLUSION: The presence of MVI or EHS in ICI-treated HCC patients may not significantly impact the occurrence of serious irAEs. However, the presence of MVI (but not EHS) in ICI-treated HCC patients may be a significant negative prognostic factor. Therefore, ICI-treated HCC patients with MVI warrant more attention.

MALAT1/ mir-1-3p mediated BRF2 expression promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. METHODS: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. RESULTS: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B­related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. CONCLUSIONS: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

The Association of Glycemic Index, Glycemic Load, and Daily Carbohydrates Intake with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.

Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. METHODS: We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74-3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47-3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55-2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36-2.49, P = 0.906). CONCLUSION: sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.

Clinical benefits of direct-acting antivirals therapy in hepatitis C virus patients with hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the present study was to evaluate the effect of direct-acting antivirals (DAAs) therapy on the clinical outcomes of hepatitis C virus (HCV) patients with hepatocellular carcinoma (HCC). METHODS: We searched multiple electronic databases from database inception to June 14, 2021. Meta-analyses were performed separately for HCC recurrence and overall survival (OS). RESULTS: A total of 23 studies were identified for the primary analysis. Compared with no intervention, pooled data showed significant benefit from DAAs therapy in reducing recurrence (adjusted HR = 0.55, 95% CI 0.41-0.74, P < 0.001; I2  = 66.6%, P < 0.001) and improving OS (adjusted HR = 0.36, 95% CI 0.16-0.83, P = 0.017; I2  = 90.7%, P < 0.001) of HCV-related HCC patients. Compared with non-responders, patients with sustained virologic response (SVR) had greater benefit from DAAs therapy in reducing recurrence (HR = 0.37, 95% CI 0.16-0.84, P = 0.017; I2  = 58.8%, P = 0.088) and improving OS (HR = 0.17; 95% CI 0.06-0.50; P = 0.001; I2  = 56.4%, P = 0.130). Though DAAs did not show significant advantages over IFN in reducing recurrence (adjusted HR = 0.96, 95% CI 0.72-1.28, P = 0.784; I2  = 0.0%, P = 0.805), there seems to be a trend toward OS benefit from DAAs therapy (adjusted HR = 0.11, 95% CI 0.01-1.19, P = 0.059). CONCLUSION: DAAs therapy can prevent recurrence and improve OS of HCV-related HCC patients, especially for patients with SVR. Further prospective randomized controlled trial is warranted to validate these results.

Oral cavity response to air pollutant exposure and association with pulmonary inflammation and symptoms in asthmatic children.

Exposure to fine particulate matter (PM2.5) and ozone (O3) may lead to inflammation and oxidative damage in the oral cavity, which is hypothesized to contribute to the worsening of airway inflammation and asthma symptoms. In this panel study of 43 asthmatic children aged 5-13 years old, each child had 4 clinic visits with a 2-week interval between two consecutive visits. At each visit, saliva samples were collected and subsequently analyzed for interleukin 6 (IL-6) and eosinophil cationic protein (ECP) as biomarkers of inflammation and malondialdehyde (MDA) as a biomarker of oxidative stress in the oral cavity. At each visit, children were measured for fractional exhaled nitric oxide (FeNO) as a marker of pulmonary inflammation. Asthma symptoms of these children were measured using the Childhood Asthma Control Test (C-ACT). We found that an interquartile range (IQR) increase in 24-h average personal exposure to PM2.5 measured 1 and 2 days prior was associated with increased salivary IL-6 concentration by 3.0% (95%CI: 0.2%-6.0%) and 4.2% (0.7%-8.0%), respectively. However, we did not find a clear association between personal O3 exposure and any of the salivary biomarkers, except for a negative association between salivary MDA and O3 exposure measured 1 day prior. An IQR increase in salivary IL-6 concentration was associated with significantly increased FeNO by 28.8% (4.3%-53.4%). In addition, we found that increasing salivary IL-6 concentrations were associated with decreased individual and total C-ACT scores, indicating the worsening of asthma symptoms. We estimated that 13.2%-22.2% of the associations of PM2.5 exposure measured 1 day prior with FeNO and C-ACT scores were mediated by salivary IL-6. These findings suggest that the induction of inflammation in the oral cavity may have played a role in linking air pollution exposure with the worsening of airway inflammation and asthma symptoms.

Size-segregated particle number concentrations and outpatient-department visits for pediatric respiratory diseases in Shanghai, China.

BACKGROUND: Few studies have simultaneously explored which size of particles has the greatest impact on the risk for pediatric asthma, bronchitis and upper respiratory tract infections (URTIs). OBJECTIVES: To investigate the short-term association between size-segregated particle number concentrations (PNCs) and outpatient-department visits (ODVs) for major pediatric respiratory diseases. METHODS: Daily counts of pediatric ODVs for asthma, bronchitis and URTIs were obtained from 66 hospitals in Shanghai, China, from 2016 to 2018. Pollutant effects were estimated using Poisson generalized additive models combined with polynomial distributed lag models. We also fitted co-pollutant cumulative effects models included six criteria air pollutants and conducted stratifying analyses by gender, age, season and geographic distances. RESULTS: We identified a total of 430,103 patients with asthma, 1,547,013 patients with bronchitis, and 2,155,738 patients with URTIs from the hospitals. Effect estimates increased with decreasing particle size. Ultrafine particle (UFP) and PNCs of 0.10-0.40 µm particles (PNC0.10-0.40) were associated with increased ODVs for asthma, bronchitis and URTIs at cumulative lags up to 3d. Associations tended to appear stable after adjusting for criteria air pollutants. At the cumulative lag 0-2d, each interquartile range increase in UFP was associated with increased ODVs due to asthma (relative risk 1.21, 95% CI: 1.07, 1.38), bronchitis (1.20, 95% CI: 1.07, 1.34) and URTI (1.17, 95% CI: 1.06, 1.30), whereas the associations for PNC0.10-0.40 remained significant but attenuated in magnitude. CONCLUSIONS: UFP may be a leading contributor to the adverse respiratory effects of particulate air pollution and the effects increased with decreasing particle size.

Cervical lymph node enlargement as the initial manifestation of rectal cancer.

BACKGROUND: Colorectal cancer is a very common malignant tumor worldwide. The clinical manifestations of advanced colorectal cancer include the changes in bowel habits, hematochezia, diarrhea, local abdominal pain and other symptoms. However, the colorectal cancer with an initial symptom of cervical lymph node enlargement is extremely rare. In this article, we report a case of rectal cancer presenting with cervical lymph nodes enlargement as the initial symptom. CASE PRESENTATION: A 57-year-old woman was admitted to our hospital for cervical lymph node enlargement which was accidentally detected during physical examination. Computed tomography scan revealed multiple enlarged lymph nodes in the neck. Cervical ultrasound showed normal thyroid gland and multiple left supraclavicular lymph nodes enlargement. The patient underwent lymph nodes biopsy and pathologic results showed metastatic adenocarcinoma. The subsequent lower gastrointestinal endoscopy revealed a mucosal bulge lesion located at rectus and biopsy revealed adenocarcinoma. The patient underwent rectal cancer resection. She is alive with no evidence of recurrence or new tumors 2 years after surgery. CONCLUSIONS: Cervical lymph node metastasis is a rare metastatic way in colorectal cancer. This is the first case of rectal cancer presenting with cervical lymph nodes metastases as the initial symptom. Surgical resection combined with postoperative chemotherapy improved long-term prognosis of the patient. This rare metastatic way of rectal cancer should be paid attention for clinicians.

Personal Exposure to PM2.5 Oxidative Potential in Association with Pulmonary Pathophysiologic Outcomes in Children with Asthma.

Fine particulate matter (PM2.5) with a higher oxidative potential has been thought to be more detrimental to pulmonary health. We aim to investigate the associations between personal exposure to PM2.5 oxidative potential and pulmonary outcomes in asthmatic children. We measured each of the 43 asthmatic children 4 times for airway mechanics, lung function, airway inflammation, and asthma symptom scores. Coupling measured indoor and outdoor concentrations of PM2.5 mass, constituents, and oxidative potential with individual time-activity data, we calculated 24 h average personal exposures 0-3 days prior to a health outcome measurement. We found that increases in daily personal exposure to PM2.5 oxidative potential were significantly associated with increased small, large, and total airway resistance, increased airway impedance, decreased lung function, and worsened scores of individual asthma symptoms and the total symptom score. Among the PM2.5 constituents, organic matters largely of indoor origin contributed the greatest to PM2.5 oxidative potential. Given that the variability in PM2.5 oxidative potential was a stronger driver than PM2.5 mass for the variability in the respiratory health outcomes, it is suggested to reduce PM2.5 oxidative potential, particularly by reducing the organic matter constituent of indoor PM2.5, as a targeted source control strategy in asthma management.

Characteristics of childhood allergic diseases in outpatient and emergency departments in Shanghai, China, 2016-2018: a multicenter, retrospective study.

BACKGROUND: The prevalence of allergic diseases (ADs), such as asthma and allergic rhinitis (AR), is increasing worldwide in both adults and children. Although ADs are common and frequently coexist in outpatient care, city-level data regarding the characteristics of childhood AD remain limited in China. This study aimed to assess the profile and characteristics of ADs in the city of Shanghai. METHODS: A multicenter retrospective study was designed to collect routine administrative data from outpatient and emergency departments from 66 hospitals in Shanghai, China, from 2016 to 2018. Children with asthma, AR, allergic conjunctivitis (AC), and allergic skin diseases were investigated. Demographic characteristics, patients visit pattern, spectrum of diagnosis, and comorbidities were analyzed. RESULTS: A total of 2,376,150 outpatient and emergency visits for ADs were included in the period from 2016 to 2018. Allergic skin diseases accounted for 38.9%, followed by asthma (34.8%), AR (22.9%), and AC (3.3%), with a male predominance in all four diseases. Asthma and allergic skin diseases were most frequent in the 1 to < 4 years of age group, while AR and AC were more common in the 4 to < 7 years of age group. Asthma accounted for the greatest number of annual and emergency visits. The most frequent comorbidity of asthma was lower respiratory tract infection (LRTI) (49.3%), followed by AR (20.5%) and upper respiratory tract infection (14.1%). The most common comorbidities of AR were otitis media (23.4%), adenoid hypertrophy/obstructive sleep apnea (22.1%), followed by LRTI (12.1%), asthma (9.4%) and chronic pharyngitis (8.9%). CONCLUSIONS: Asthma and allergic skin diseases were the most common ADs in outpatient and emergency departments in the study period. Respiratory tract infection was the most common comorbidity of asthma in children. More attention should be devoted to the treatment of comorbidities to improve childhood AD outcomes with a better understanding of the characteristics of ADs in outpatient care.

Temperature changes between neighboring days and childhood asthma: a seasonal analysis in Shanghai, China.

Few evidences are available about the impact of temperature variation on childhood asthma in different seasons. This study aimed to assess the influence of temperature changes between neighboring days (TCN) on the exacerbation of asthma among children. Daily outpatient visits for childhood asthma (DOVCA) were collected from 17 main hospitals in Shanghai, China, from 2016 to 2018. A quasi-Poisson regression combined with distributed lagged nonlinear models was employed to estimate the association between TCN and asthma visits in cool or warm seasons, after controlling for short- and long-term trends, day of week, holidays, daily mean temperature, daily mean relative humidity, and air pollutants. The TCN varied from - 9.6 to 6.7 °C. The relationship between TCN and DOVCA greatly varied by season. In warm seasons, positive TCN (temperature rise) was associated with higher risks of asthma outpatient visits and negative TCN (temperature drop) was associated with lower risks; the associations were present on lag 1 day and lasted for 2 weeks; the cumulative relative risk of childhood asthma over 0 to 14 days was 1.98 (95% confidence interval: 1.42, 2.76) and 0.31 (95% confidence intervals: 0.21, 0.44) comparing a TCN of 2.5 °C (5th percentile) and - 3.2 °C (95th percentile) with 0 °C, respectively. In cool seasons, neither negative nor positive TCN showed significant risks. In conclusion, temperature rise might increase the risk of childhood asthma exacerbation and temperature drop might decrease the risks in warm seasons. There were no statistically significant influences in cool seasons.

[Review of and Reflections on the Current Status of Childhood Asthma Diagnosis and Treatment in China].

Over the last decades, the overall prevalence of childhood asthma in China has been on the rise, and the level of diagnosis and treatment of asthma has also shown significant improvement. However, the overall control of childhood asthma in China has not yet reached the ideal level. The main causes are as follows: due to high social pressure and other factors, the accurate diagnosis of childhood asthma by clinicians is still insufficient; clinicians do not have sufficient understanding of environmental pollution and other controllable factors that may affect the rising prevalence of childhood asthma and poor asthma control; the standardization of clinical asthma treatment needs to be further improved. Clinicians should improve their understanding of childhood asthma, formulate therapeutic regimes based on the guidelines, and constantly improve the management of childhood asthma.

Malondialdehyde in Nasal Fluid: A Biomarker for Monitoring Asthma Control in Relation to Air Pollution Exposure.

Fine particulate matter (PM2.5) and ozone (O3) may exert oxidative damage in the nose, which is hypothesized to be associated with worsened asthma symptoms. This study, hence, is to explore whether an oxidative stress biomarker, malondialdehyde (MDA) in the nasal fluid, has the potential to aid personalized asthma control. In a panel study of 43 asthmatic children, 5-13 years old, each child was measured 4 times with a 2-week interval between consecutive clinic visits. At each visit, nasal fluid and urine samples were collected, and fractional exhaled nitric oxide (FeNO) was measured as a biomarker of pulmonary inflammation. In addition to nasal MDA, urinary MDA and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured as biomarkers of systemic oxidative stress. We also assessed asthma symptoms using the Childhood Asthma-Control Test (C-ACT). We found that interquartile range (IQR) increases in 24 h average personal PM2.5 exposure (22.2-33.5 µg/m3), estimated 0 to 5 days prior to a clinic visit, were associated with increased nasal MDA concentrations by 38.6-54.9%. Similarly, IQR increases in 24 h average personal O3 exposure (7.7-8.2 ppb) estimated 2 to 4 days prior were associated with increased nasal MDA by 22.1-69.4%. Only increased PM2.5 exposure was associated with increased FeNO. Increased nasal MDA concentration was associated with decreased total and individual C-ACT scores, indicating worsening of asthma symptoms. However, no significant associations were observed between urinary MDA or 8-OHdG and C-ACT scores. The results confirm that oxidative stress plays an important role in linking air pollution exposure and adverse respiratory health effects. These findings support that MDA in the nasal fluid may serve as a useful biomarker for monitoring asthma status, especially in relation to PM2.5 and O3 exposures, two known risk factors of asthma exacerbation.

Chinese guidelines for childhood asthma 2016: Major updates, recommendations and key regional data.

OBJECTIVE: With increased industrialization and urbanization in China, pediatric asthma is becoming more prevalent. Despite a growing body of evidence, there remains a significant unmet need for adequate management of childhood asthma. The Subspecialty Group of Respiratory Diseases of the Society of Pediatrics, the Chinese Medical Association, and the editorial board of the Chinese Journal of Pediatrics have recently updated the "Guidelines for diagnosis and optimal management of asthma in children," first published in 2008. METHODS: This article reviews the major updates to the guidelines and covers the main recommendations for diagnosis, assessment, and treatment of pediatric asthma in China. Key regional data on epidemiology, clinical features, disease burden, knowledge among children and parents, and risk factors including pollution are provided to contextualize the recommendations. RESULTS: The major updates to the guidelines include: (1) A more practical definition of asthma; (2) assessment of asthma control that takes into account both current symptom control and future risk; (3) classification based on disease severity that corresponds with treatment step; (4) differentiation between difficult-to-treat and poorly controlled asthma; (5) an open-ended approach to pharmacological management; and (6) allergen immunotherapy (AIT) in mild- to moderate-persistent asthma. CONCLUSIONS: The updated "Guidelines for the diagnosis and optimal management of asthma in children (2016)" combine the latest national and international clinical evidence and experience to provide practical and reliable recommendations to Chinese clinicians.

Risk Factors in Preschool Children for Predicting Asthma During the Preschool Age and the Early School Age: a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The aim of this study was to identify risk factors of asthma among children < 6 years old (preschool age) for predicting asthma during the preschool age and early school age (≤ 10 years of age). METHOD OF THE STUDY: MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017. Prospective or retrospective cohort and case-control studies were included. Studies had to have evaluated risk factors or a predictive model for developing asthma in children ≤ 6 years of age or persistent asthma in early school age. RECENT FINDINGS: A total of 17 studies were included in the analysis. Factors associated with developing asthma in children ≤ 10 years of age (both pre-school and early school age) included male gender (pooled OR = 1.70, P < 0.001), atopic dermatitis (pooled OR = 2.02, P < 0.001), a family history of asthma (pooled OR = 2.20, P < 0.001), and serum IgE levels ≥ 60 kU/l or having specific IgE (pooled OR = 2.36, P < 0.001). A history of exposure to smoke or wheezing was also associated with persistent asthma in early school age (pooled OR = 1.51, P = 0.030 and pooled OR = 2.59, P < 0.001, respectively). In general, asthma predictive models (e.g., API, PIAMA, PAPS) had relatively low sensitivity (range, 21% to 71.4%) but high specificity (range, 69% to 98%). The study found that male gender, exposure to smoke, atopic dermatitis, family history of asthma, history of wheezing, and serum IgE level ≥ 60 kU/l or having specific IgE were significantly associated with developing asthma by either preschool or early school age. Asthma predictive models can be developed by those risk factors.

Uncontrolled asthma and its risk factors in Chinese children: A cross-sectional observational study.

OBJECTIVE: Asthma afflicts many children in China but information about asthma management among Chinese pediatric asthma patients is limited. This study aims to evaluate asthma control among Chinese pediatric patients and identify risk factors associated with uncontrolled asthma. METHODS: A total of 4223 patients with persistent asthma aged 2-16 years from 42 tertiary hospitals across all regions of mainland China except Tibet were surveyed. Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT) and Global Initiative for Asthma (GINA) criteria were used to assess asthma control for children aged 12-16 years, 4-11 years and 2-3 years, respectively. Uncontrolled asthma was defined as ACT or C-ACT score ≤19 or GINA-defined uncontrolled asthma. Risk factors associated with uncontrolled asthma were identified using multivariate logistic regression models. RESULTS: Asthma was uncontrolled in 19.9% of the subjects. High rates of uncontrolled asthma were found in subjects with treatment non-adherence (44.1%), concomitant allergic rhinitis (AR) (23.3%), disease duration ≥ 1.5 years (22.8%), and first-degree relatives with AR (21.5%). The risk of uncontrolled asthma was much higher in the treatment non-adherence group compared to the complete adherence group (OR = 5.79, p < 0.001). Concomitant AR, disease duration ≥ 1.5 years, and first-degree relatives with AR were also confirmed as risk factors associated with uncontrolled asthma. CONCLUSIONS: About 20% of Chinese pediatric asthma patients had uncontrolled asthma. Treatment adherence and AR were the most significant risk factors. Tailored measures aimed at improving treatment adherence and diagnosis and treatment of AR should be adopted to improve the level of asthma control in Chinese children.

Budesonide suspension nebulization treatment in Chinese pediatric patients with cough variant asthma: a multi-center observational study.

OBJECTIVE: To describe the impact of nebulized budesonide inhalation suspension (BIS) on guardian-reported symptoms in Chinese pediatric patients with cough variant asthma (CVA). METHODS: This was a secondary analysis of a prospective, non-interventional study conducted at 39 Chinese sites. Patients with CVA aged ≤5 years were classified according to the severity of baseline symptoms: mild (symptom score ≤3) or severe (symptom score >3). Daytime and night-time symptom scores, disease control, use of bronchodilators, and improvements in symptoms control were compared after 1, 3, 5 and 7 weeks of treatment between groups. RESULTS: Among 914 patients, 821 (89.8%) completed the 7-week treatment. Among all patients, 368 (40.3%) were classified as mild CVA and 529 (57.9%), as severe CVA. Symptom scores in the severe group were higher than those in the mild group at weeks 1, 3, and 5 (p < 0.05), but not at week 7 (p > 0.05). Further, more patients in the mild group achieved disease control at any time point (98.6% at 3 weeks and 99.7% at 7 weeks), compared with the patients in the severe group (p < 0.001). The proportion of patients requiring bronchodilators differed between the groups until week 5 (p < 0.001). No severe or drug-related adverse events were reported. CONCLUSIONS: Individualized BIS treatment should be formulated according to the severity of baseline symptoms in CVA patients. Patients with mild CVA showed improvement after a shorter treatment time, while patients with severe CVA might require a longer time to respond to the treatment.

Comprehensive molecular analysis identifies RET alterations association with response of ICIs in multi-immunotherapy cohorts.

BACKGROUND: The RET gene, which is frequently mutated across many types of cancer, has been proven to be critically involved in tumorigenesis and tumour development; however, its prediction of the therapeutic efficacy of immune checkpoint inhibitor (ICI) therapy remains to be elucidated. The present research aims to investigate the association between RET mutations and the efficiency of ICI therapy. METHOD: We analysed the role of RET mutations in predicting the prognosis of patients receiving ICIs therapy in the discovery cohort and validated it in the validation cohort. Then, multi-omics data from TCGA pan-cancer cohort was employed to propose the association between RET mutations and tumour inflamed anti-tumour immune response and tumour antigenicity. RESULTS: Our study revealed that among 606 cases and across five types of cancer, RET mutation was associated with better clinical outcomes for ICIs therapy, including elevated response rate, longer progression-free survival PFS, and longer overall survival OS. Multivariate analysis showed that RET mutation could independently predict the prognosis of patients treated with ICIs, after adjusting cancer types. The predictive value of RET status for the OS of patients treated with ICIs immunotherapy was further validated in the validation cohort (n = 1,409). Subgroup analysis suggested that only the monotherapy group showed significant differences in OS(P < 0.05) and PFS(P < 0.05) between RET-wildtype tumours and RET-mutant tumours. Multi-omics data analysis revealed potential anti-tumour immunity mechanisms of RET mutations, suggesting that RET-mutant tumours have enhanced immunogenicity, higher expression of immune checkpoints and chemokines, and higher immune cell infiltration than those observed in RET-wildtype tumours; thus, potentially indicating a more favourable response to immunotherapy. CONCLUSIONS: RET mutation may be a predictive biomarker of enhanced response to ICIs therapy. Extensive investigation of the underlying molecular mechanisms and prospective studies are needed in the future.