Divergent effects of sex on hippocampal subfield alterations in drug-naive patients with major depressive disorder.

BACKGROUND: The hippocampus is a crucial brain structure in etiological models of major depressive disorder (MDD). It remains unclear whether sex differences in the incidence and symptoms of MDD are related to differential illness-associated brain alterations, including alterations in the hippocampus. This study investigated divergent the effects of sex on hippocampal subfield alterations in drug-naive patients with MDD. METHODS: High-resolution structural MR images were obtained from 144 drug-naive individuals with MDD early in their illness course and 135 age- and sex-matched healthy controls (HCs). Hippocampal subfields were segmented using FreeSurfer software and analyzed in terms of both histological subfields (CA1-4, dentate gyrus, etc.) and more integrative larger functional subregions (head, body and tail). RESULTS: We observed a significant overall reduction in hippocampal volume in MDD patients, with deficits more prominent deficits in the posterior hippocampus. Differences in anatomic alterations between male and female patients were observed in the CA1-head, presubiculum-body and fimbria in the left hemisphere. Exploratory analyses revealed different patterns of clinical and memory function correlations with histological subfields and functional subregions between male and female patients primarily in the hippocampal head and body. LIMITATIONS: This cross-sectional study cannot clarify the causality of hippocampal alterations or their association with illness risk or onset. CONCLUSIONS: These findings represent the first reported sex-specific alterations in hippocampal histological subfields in patients with MDD early in the illness course prior to treatment. Sex-specific hippocampal alterations may contribute to diverse sex differences in the clinical presentation of MDD.

Distinctive intrinsic functional connectivity alterations of anterior cingulate cortex subdivisions in major depressive disorder: A systematic review and meta-analysis.

Evidence of whether the intrinsic functional connectivity of anterior cingulate cortex (ACC) and its subregions is altered in major depressive disorder (MDD) remains inconclusive. A systematic review and meta-analysis were therefore performed on the whole-brain resting-state functional connectivity (rsFC) studies using the ACC and its subregions as seed regions in MDD, in order to draw more reliable conclusions. Forty-four ACC-based rsFC studies were included, comprising 25 subgenual ACC-based studies, 11 pregenual ACC-based studies, and 17 dorsal ACC-based studies. Specific alterations of rsFC were identified for each ACC subregion in patients with MDD, with altered rsFC of subgenual ACC in emotion-related brain regions, of pregenual ACC in sensorimotor-related regions, and of dorsal ACC in cognition-related regions. Furthermore, meta-regression analysis revealed a significant negative correlation between the pgACC-caudate hypoconnectivity and percentage of female patients in the study cohort. This meta-analysis provides robust evidence of altered intrinsic functional connectivity of the ACC subregions in MDD, which may hold relevance to understanding the origin of, and treating, the emotional, sensorimotor and cognitive dysfunctions that are often observed in these patients.

The P2 nucleic acid binding protein of Sugarcane bacilliform virus is a viral pathogenic factor.

Background: Saccharum spp. is the primary source of sugar and plays a significant role in global renewable bioenergy. Sugarcane bacilliform virus (SCBV) is one of the most important viruses infecting sugarcane, causing severe yield losses and quality degradation. It is of great significance to reveal the pathogenesis of SCBV and resistance breeding. However, little is known about the viral virulence factors or RNA silencing suppressors and the molecular mechanism of pathogenesis. Methods: To systematically investigate the functions of the unknown protein P2 encoded by SCBV ORF2. Phylogenetic analysis was implemented to infer the evolutionary relationship between the P2 of SCBV and other badnaviruses. The precise subcellular localization of P2 was verified in the transient infiltrated Nicotiana benthamiana epidermal mesophyll cells and protoplasts using the Laser scanning confocal microscope (LSCM). The post-transcriptional gene silencing (PTGS) and transcriptional gene silencing (TGS) RNA silencing suppressor activity of P2 was analyzed, respectively. Furthermore, restriction digestion and RT-qPCR assays were conducted to verify the probable mechanism of P2 on repressing DNA methylation. To explore the pathogenicity of P2, a potato virus X-based viral vector was used to heterologously express SCBV P2 and the consequent H2O2 accumulation was detected by the 3,3'-diaminobenzidine (DAB) staining method. Results: Phylogenetic analysis shows that SCBV has no obvious sequence similarity and low genetic relatedness to Badnavirus and Tungrovirus representatives. LSCM studies show that P2 is localized in both the cytoplasm and nucleus. Moreover, P2 is shown to be a suppressor of PTGS and TGS, which can not only repress ssRNA-induced gene silencing but also disrupt the host RNA-directed DNA methylation (RdDM) pathway. In addition, P2 can trigger an oxidative burst and cause typical hypersensitive-like response (HLR) necrosis in systemic leaves of N. benthamiana when expressed by PVX. Overall, our results laid a foundation for deciphering the molecular mechanism of SCBV pathogenesis and made progress for resistance breeding.

Screening and Identification of Host Factors Interacting with the Virulence Factor P0 Encoded by Sugarcane Yellow Leaf Virus by Yeast Two-Hybrid Assay.

Sugarcane yellow leaf virus (SCYLV), a member of the genus Polerovirus in the family Luteoviridae, causes severe damage and represents a great threat to sugarcane cultivation and sugar industry development. In this study, inoculation of Nicotiana benthamiana plants with a potato virus X (PVX)-based vector carrying the SCYLV P0 gene induced typical mosaic, leaf rolling symptoms and was associated with a hypersensitive-like response (HLR) necrosis symptom, which is accompanied with a systemic burst of H2O2 and also leads to higher PVX viral genome accumulation levels. Our results demonstrate that SCYLV P0 is a pathogenicity determinant and plays important roles in disease development. To further explore its function in pathogenic processes, a yeast two-hybrid assay was performed to screen the putative P0-interacting host factors. The recombinant plasmid pGBKT7-P0 was constructed as a bait and transformed into the yeast strain Y2HGold. The ROC22 cultivar (an important parental resource of the main cultivar in China) cDNA prey library was constructed and screened by co-transformation with the P0 bait. We identified 28 potential interacting partners including those involved in the optical signal path, plant growth and development, transcriptional regulation, host defense response, and viral replication. To our knowledge, this is the first time we have reported the host proteins interacting with the P0 virulence factor encoded by sugarcane yellow leaf virus. This study not only provides valuable insights into elucidating the molecular mechanism of the pathogenicity of SCYLV, but also sheds light on revealing the probable new pathogenesis of Polerovirus in the future.

Suprachiasmatic nucleus functional connectivity related to insomnia symptoms in adolescents with major depressive disorder.

Background: Insomnia is a commonly seen symptom in adolescents with major depressive disorder (MDD). The suprachiasmatic nucleus (SCN), which is the circadian rhythm regulation center, plays a crucial role in the regulation of sleep-wake circulation. Nevertheless, how SCN function contributes to the exact neural mechanisms underlying the associations between insomnia and depressive symptoms has not been explored in adolescents. In the current study, we aimed to explore the relationship between SCN functional connectivity (FC) and insomnia symptoms in adolescents with MDD using a seed-based FC method. Methods: In the current study, we recruited sixty-eight first-episode drug-naïve adolescents with MDD and classified them into high insomnia (MDD-HI) and low insomnia (MDD-LI) groups according to the sleep disturbance subscale of the Hamilton Depression Rating Scale (HAMD-S). Forty-three age/gender-matched healthy controls (HCs) were also recruited. SCN FC maps were generally for all subjects and compared among three groups using one-way ANOVA with age, gender and adjusted HAMD score as covariates. We used partial correlations to explore associations between altered FC and clinical symptoms, including sleep quality scores. Results: Adolescents with MDD showed worse sleep quality, which positively correlated with the severity of depression. Compared to MDD-LI and HCs, MDD-HI adolescents demonstrated significantly decreased FC between the right SCN and bilateral precuneus, and there was no significant difference between the MDD-LI and HC groups. The HAMD-S scores were negatively correlated with bilateral SCN-precuneus connectivity, and the retardation factor score of HAMD was negatively correlated with right SCN-precuneus connectivity. Conclusion: The altered FC between the SCN and precuneus may underline the neural mechanism of sleep-related symptoms in depressive adolescents and provide potential targets for personalized treatment strategies.

Comparison the acute toxicity of two different induction chemotherapy schedules with cisplatin and fluorouracil in nasopharyngeal carcinoma patients.

PURPOSE: To compare the acute toxicity of two different induction chemotherapy (IndCT) regimen followed by the same IMRT in patients with advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From July 2015 to December 2016, 110 NPC patients with stage III-IV diseases were prospectively randomized to receive either a conventional triweekly cisplatin + 5-fluorouracil (PF) for 3 cycles or weekly P-F for 10 doses, followed by the same IMRT to both arms. The primary endpoints of this study were grade 3/4 and any grade acute toxicities during IndCT period. The secondary endpoints included tumor response and various survivals. RESULTS: Baseline patient characteristics were comparable in both groups. Patients who received weekly P-F experienced significant reduction of grade 3/4 acute toxicities, including neutropenia (12.7% vs. 40.0%, P = 0.0012), anorexia (0% vs. 14.6%, P = 0.0059), mucositis (0% vs. 14.6%, P = 0.0059), and hyponatremia (0% vs. 16.4%, P = 0.0027), compared with the triweekly PF group, resulting in fewer IndCT interruptions (1.8% vs. 16.4%, P = 0.0203), emergency room visits (0% vs. 12.7%, P = 0.0128), and additional hospitalizations (0% vs. 9.1%, P = 0.0568). The acute toxicities during IMRT period were similar. Weekly P-F arm had higher complete response rates (83.6% vs. 61.8%, P = 0.0152) and lower relapse rates (16.4% vs. 33.3%, P = 0.0402) after a median follow-up of 67 months. Kaplan-Meier survival analyses revealed a better trend of locoregional failure-free (P = 0.0892), distant metastasis failure-free (P = 0.0775), and progression-free (P = 0.0709) survivals, favoring the weekly P-F arm. CONCLUSION: IndCT of weekly schedule does reduce acute toxicities without compromised tumor response and survivals.

Abnormal focal segments in left uncinate fasciculus in adults with obsessive-compulsive disorder.

Background: Although the specific role of the uncinate fasciculus (UF) in emotional processing in patients with obsessive-compulsive disorder (OCD) has been investigated, the exact focal abnormalities in the UF have not been identified. The aim of the current study was to identify focal abnormalities in the white matter (WM) microstructure of the UF and to determine the associations between clinical features and structural neural substrates. Methods: In total, 71 drug-naïve patients with OCD and 81 age- and sex-matched healthy controls (HCs) were included. Automated fiber quantification (AFQ), a tract-based quantitative approach, was adopted to measure alterations in diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), along the trajectory of the UF. Additionally, we utilized partial correlation analyses to explore the relationship between the altered diffusion parameters and clinical characteristics. Results: OCD patients showed significantly higher FA and lower RD at the level of the temporal and insular portions in the left UF than HCs. In the insular segments of the left UF, increased FA was positively correlated with the Hamilton Anxiety Scale (HAMA) score, while decreased RD was negatively correlated with the duration of illness. Conclusion: We observed specific focal abnormalities in the left UF in adult patients with OCD. Correlations with measures of anxiety and duration of illness underscore the functional importance of the insular portion of left UF disturbance in OCD patients.

Comparison of Bacteriology Between Eosinophilic and Noneosinophilic Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVE: To compare culture results between eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (ECRSwNP) and noneosinophilic CRS with nasal polyps (nECRSwNP). STUDY DESIGN: Retrospective study. SETTING: Tertiary medical center. METHODS: We retrospectively analyzed a cohort of CRSwNP patients undergoing primary functional endoscopic sinus surgery. Prior to surgery, swab samples for bacterial culture were collected from their middle meatus using cotton tips. After surgery, postoperative specimens were histologically examined for tissue eosinophilia. A tissue eosinophil density of >10 cells at high power magnification was used to discriminate between ECRSwNP and nECRSwNP. RESULTS: A total of 295 patients were studied with polyps present on 471 sides of the nasal cavity. Among them, 236 sides were ECRSwNP, and the remaining 235 sides were nECRSwNP. Bacterial growth was found in 94 ECRSwNP sides, and in 88 nECRSwNP sides. Culture rates were similar between ECRSwNP and nECRSwNP sides (p = .595). However, Gram-negative aerobes were found in 25 of 236 ECRSwNP sides, and in 42 of 235 nECRSwNP sides. The Gram-negative culture rate was significantly higher in nECRSwNP than in ECRSwNP sides (p = .024). CONCLUSION: The bacteriology of CRS was different between ECRSwNP and nECRSwNP. The Gram-negative aerobes were present more in nECRSwNP than in ECRSwNP.

Heparan sulfate regulates IL-21 bioavailability and signal strength that control germinal center B cell selection and differentiation.

In antibody responses, mutated germinal center B (BGC) cells are positively selected for reentry or differentiation. As the products from GCs, memory B cells and antibody-secreting cells (ASCs) support high-affinity and long-lasting immunity. Positive selection of BGC cells is controlled by signals received through the B cell receptor (BCR) and follicular helper T (TFH) cell-derived signals, in particular costimulation through CD40. Here, we demonstrate that the TFH cell effector cytokine interleukin-21 (IL-21) joins BCR and CD40 in supporting BGC selection and reveal that strong IL-21 signaling prioritizes ASC differentiation in vivo. BGC cells, compared with non-BGC cells, show significantly reduced IL-21 binding and attenuated signaling, which is mediated by low cellular heparan sulfate (HS) sulfation. Mechanistically, N-deacetylase and N-sulfotransferase 1 (Ndst1)-mediated N-sulfation of HS in B cells promotes IL-21 binding and signal strength. Ndst1 is down-regulated in BGC cells and up-regulated in ASC precursors, suggesting selective desensitization to IL-21 in BGC cells. Thus, specialized biochemical regulation of IL-21 bioavailability and signal strength sets a balance between the stringency and efficiency of GC selection.

Effect of Functional Endoscopic Sinus Surgery on Gustatory Function in Patients With Chronic Rhinosinusitis.

OBJECTIVES: In this study, we investigated the effect of functional endoscopic sinus surgery (FESS) on gustatory function in patients with chronic rhinosinusitis (CRS). METHODS: Forty-three patients with CRS who underwent FESS were included in this study. Prior to FESS and 3 months after surgery, the severity of rhinosinusitis was assessed using the Taiwanese version of the 22-item SNOT (SNOT-22), endoscopic examination, and acoustic rhinometry. The olfactory function was evaluated using the phenylethyl alcohol odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test, and the gustatory function was evaluated using the whole mouth suprathreshold taste test (WMTT) and the taste quad test (TQT). Subgroup analyses were performed based on CRS phenotypes and endotypes. RESULTS: The SNOT-22 significantly improved 3 months after FESS for all patients with CRS. The endoscopic score and olfactory function significantly improved in patients with eosinophilic CRS and in patients with nasal polyps (CRSwNP). The WMTT sweet and bitter scores were significantly lower after FESS in CRSwNP, but the TQT sweet score was significantly higher in patients without nasal polyps. In addition, patients with noneosinophilic CRS had significantly decreased WMTT and salty scores 3 months after FESS. CONCLUSION: Our results showed that the effect of FESS on gustatory function of patients with CRS was different with the different testing procedures, the association with nasal polyps, and the underlying inflammatory patterns.

Multivariate associations between behavioural dimensions and white matter across children and adolescents with and without attention-deficit/hyperactivity disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder. Integrity of white matter microstructure plays a key role in the neural mechanism of ADHD presentations. However, the relationships between specific behavioural dimensions and white matter microstructure are less well known. This study aimed to identify associations between white matter and a broad set of clinical features across children and adolescent with and without ADHD using a data-driven multivariate approach. METHOD: We recruited a total of 130 children (62 controls and 68 ADHD) and employed regularized generalized canonical correlation analysis to characterize the associations between white matter and a comprehensive set of clinical measures covering three domains, including symptom, cognition and behaviour. We further applied linear discriminant analysis to integrate these associations to explore potential developmental effects. RESULTS: We delineated two brain-behaviour dimensional associations in each domain resulting a total of six multivariate patterns of white matter microstructural alterations linked to hyperactivity-impulsivity and mild affected; executive functions and working memory; externalizing behaviour and social withdrawal, respectively. Apart from executive function and externalizing behaviour sharing similar white matter patterns, all other dimensions linked to a specific pattern of white matter microstructural alterations. The multivariate dimensional association scores showed an overall increase and normalization with age in ADHD group while remained stable in controls. CONCLUSIONS: We found multivariate neurobehavioral associations exist across ADHD and controls, which suggested that multiple white matter patterns underlie ADHD heterogeneity and provided neural bases for more precise diagnosis and individualized treatment.

Efficacy and safety of repetitive transcranial magnetic stimulation in children and adolescents with depression: A systematic review and preliminary meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) benefits adults with depression while its efficacy and safety in children and adolescents with major depressive disorder (MDD) remain unclear. We conducted a preliminary meta-analysis here to objectively appraise rTMS in the youth with MDD to inform future research and clinical practice. METHODS: We searched Pubmed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their inception to December 1, 2021. Studies with a control group or self-controlled designs and evaluating the Hamilton Depression Scale (HAM-D) or the Children's Depression Rating Scale-Revised (CDRS-R) at baseline and post-rTMS treatment were included. Two reviewers independently selected eligible studies, retrieved data in a structured fashion and assessed studies' quality. Hedges'g with 95 % confidence intervals and withdrawal rate with 95 % confidential intervals were separately used to evaluate the efficacy and safety of rTMS. RESULTS: Thirteen studies with six datasets (165 patients, 61.8 % female, age range from 10 to 25 years old) were included and our meta-analysis found children and adolescents with MDD benefited from rTMS treatment (Hedges'g 1.37, 95 % CI 0.85 to 1.90, P = 0.001). In addition, 4 % of patients (95 % CI 0.02 to 0.09) withdrew during rTMS treatment for reasons including fear, mood swings, suicide ideation and adverse events. LIMITATIONS: This conclusion is tempered by a small number of studies included and a potentially existing placebo effect. CONCLUSIONS: Our findings suggest rTMS could benefit children and adolescents with MDD in a relatively safe manner, and this result may help guide clinical practice.

Aberrant intrinsic hippocampal and orbitofrontal connectivity in drug-naive adolescent patients with major depressive disorder.

Alterations in resting-state functional connectivity (rsFC) of hippocampus and orbitofrontal cortex (OFC) have been highly implicated in major depressive disorder (MDD) and the researches have penetrated to the subregional level. However, relatively little is known about the intrinsic connectivity patterns of these two regions in adolescent MDD (aMDD), especially that of their functional subregions. Therefore, in the current study, we recruited 68 first-episode drug-naive aMDD patients and 43 matched typically developing controls (TDC) to characterize the alterations of whole-brain rsFC patterns in hippocampus and OFC at both regional and subregional levels in aMDD. The definition of specific functional subregions in hippocampus and OFC were based on the prior functional clustering-analysis results. Furthermore, the relationship between rsFC alterations and clinical features was also explored. Compared to TDC group, aMDD patients showed decreased connectivity of the left whole hippocampus with bilateral OFC and right inferior temporal gyrus at the regional level and increased connectivity between one of the right hippocampal subregions and right posterior insula at the subregional level. Reduced connectivity of OFC was only found in the subregion of left OFC with left anterior insula extending to lenticula in aMDD patients relative to TDC group. Our study identifies that the aberrant hippocampal and orbitofrontal rsFC was predominantly located in the insular cortex and could be summarized as an altered hippo-orbitofrontal-insular circuit in aMDD, which may be the unique features of brain network dysfunction in depression at this particular age stage. Moreover, we observed the distinct rsFC alterations in adolescent depression at the subregional level, especially the medial and lateral OFC.

Disorganized functional architecture of amygdala subregional networks in obsessive-compulsive disorder.

A precise understanding of amygdala-centered subtle networks may help refine neurocircuitry models of obsessive-compulsive disorder (OCD). We applied connectivity-based parcellation methodology to segment the amygdala based on resting-state fMRI data of 92 medication-free OCD patients without comorbidity and 90 matched healthy controls (HC). The amygdala was parcellated into two subregions corresponding to basolateral amygdala (BLA) and centromedial amygdala (CMA). Amygdala subregional functional connectivity (FC) maps were generated and group differences were evaluated with diagnosis-by-subregion flexible factorial ANOVA. We found significant diagnosis × subregion FC interactions in insula, supplementary motor area (SMA), midcingulate cortex (MCC), superior temporal gyrus (STG) and postcentral gyrus (PCG). In HC, the BLA demonstrated stronger connectivity with above regions compared to CMA, whereas in OCD, the connectivity pattern reversed to stronger CMA connectivity comparing to BLA. Relative to HC, OCD patients exhibited hypoconnectivity between left BLA and left insula, and hyperconnectivity between right CMA and SMA, MCC, insula, STG, and PCG. Moreover, OCD patients showed reduced volume of left BLA and right CMA compared to HC. Our findings characterized disorganized functional architecture of amygdala subregional networks in accordance with structural defects, providing direct evidence regarding the specific role of amygdala subregions in the neurocircuitry models of OCD.

[Effect of Family Function on Suicide-Related Behaviors of Junior Middle School Students: The Mediating Effect of Depression].

Objective: To examine the prevalence of suicide-related behaviors among junior middle school students, and to explore the mediating role of depression in the relationship between suicide-related behaviors and family function. Methods: A total of 2572 junior middle school students from three middle schools in Chengdu were interviewed face-to-face by using suicide-related items from Youth Risk Behavior Surveillance System (YRBSS), Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC). The mediating role of depression was analyzed with structural equation model. Results: The prevalence of suicide-related behaviors was 26.01% among the respondents. The prevalence of suicide ideation, suicide plan and suicide attempt were 24.38%, 13.49% and 10.77%, respectively. Depression played a partial mediating role in how family function impacted on suicide-related behaviors, presenting a direct effect value of 0.170 (95% CI: 0.117-0.218, P<0.001) and an indirect effect value of 0.205 (95% CI: 0.176-0.234, P<0.001), with the mediating effect accounting for 54.67% of the total effect. Conclusion: Poor family function may increase the risk of suicide-related behaviors, and this effect is produced mostly through the impact on children's mental health. Improving family function will not only improve children's psychological status, but also reduce suicide-related behaviors.

The expression profile of plasmatic exosomal lncRNAs in early-onset preeclampsia by sequencing.

Identification of the expression profile of exosomal lncRNAs in plasma from PE patients to provide new insights into the molecular mechanism. Five pregnant patients with early-onset severe PE were included in the PE group and 5 normal pregnant patients were included in the control group in the training cohort. Differential expression of genes were identified between the two groups, and were verified in plasma exosomes from 12 additional pregnant patients with EPE and 12 normal pregnant patients. KEGG pathway analysis and GO enrichment analysis were performed using online prediction databases to construct a lncRNA-miRNA-mRNA co-expression network. From there a panel of candidate lncRNAs was selected and validated via quantitative PCR in the two groups. In the 289 differential lncRNA, 155 were up-regulated and 134 were down-regulated. Bioinformatics enrichment analysis demonstrated that the target genes of differential expression of lncRNAs were enriched in 159 pathways with P < 0.05, including cancer, metabolic and PI3K-Akt signaling pathways. Three lncRNAs exhibited significant differential expressed in exosomes between the two groups. A lncRNA-miRNA-mRNA co-expression network analysis showed that ENST00000559730-hsa-miR-661-NUDT16 was the most frequently associated with susceptibility-relation of PE. The significant differences of plasmatic exosomal lncRNA expression between normal pregnant women and early-onset severe PE patients suggest that lncRNA may participate in the pathogenetic process of PE. Our study provides a preliminary bioinformatic foundation in order to find PE markers in plasma which further increase the sample size, and continue to verify the function of lncRNA in vitro.

An Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events: A Descriptive Analysis.

Introduction: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management. Methods: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019. Data were summarized using descriptive statistics with odds ratios for associations between patient features and hospitalization after UCC evaluation. Results: We identified 494 encounters from 289 individual patients over the study period. A history of ICI therapy was noted in 34% (n = 170/494) of encounters and 29 encounters (29/170, 17%) were confirmed and treated as irAEs. For those treated for irAEs, the majority (n = 19/29; 66%) were discharged home. Having an irAE was associated with an increased risk of hospitalization compared to non-irAEs (OR 5.66; 95% CI 2.15−14.89; p < 0.001). Conclusion: In this single institution experience, the majority of UCC encounters for confirmed irAEs were safely managed within the UCC. In ICI-treated patients, having an irAE was associated with an increased risk of hospitalization versus non-irAEs.

Validation of the traditional Chinese version of the Sinus and Nasal Quality of Life Survey (SN-5) for children.

BACKGROUND: Persistent sinonasal symptoms are common in children with chronic rhinosinusitis. The Sinus and Nasal Quality of Life (QoL) Survey (SN-5) was the first validated questionnaire measuring sinonasal-related QoL in populations aged 2-12 years. No norm has been established for Chinese-speaking countries. We translated the SN-5 into traditional Chinese and evaluated validity and reliability. METHODS: From December 2016 to December 2017, healthy volunteers and children with persistent sinonasal symptoms were enrolled. Guardians of the participants completed the SN-5, a visual analog scale (VAS) of nasal symptoms, and the Obstructive Sleep Apnea-18 (OSA-18); the responses were used to assess internal consistency, discriminant validity, and treatment responsiveness. A nontreatment group was administered the SN-5 1 week later to assess test-retest reliability. RESULTS: We recruited 31 healthy volunteers and 85 children with rhinosinusitis, 50 and 35 in the treatment and nontreatment groups, respectively. The SN-5 demonstrated good internal consistency (Cronbach's α = 0.86) and test-retest reliability (0.74, p < 0.01). It exhibited good discriminant validity between the healthy and rhinosinusitis groups (p < 0.001). The SN-5 scores were correlated with the VAS scores (0.63, p < 0.001). The effect size of the SN-5 scores was 0.51. The total SN-5 and OSA-18 scores changed significantly after 4-week treatment (p < 0.05) and demonstrated good responsiveness. The SN-5 and OSA-18 scores were significantly and positively correlated (r2 = 0.53, p < 0.001). CONCLUSION: Our traditional Chinese version of the SN-5 is reliable and valid for measuring sinonasal-related QoL in children in Chinese-speaking countries. TRIAL REGISTRATION NUMBER: NCT04836403.

Maintenance metronomic chemotherapy for metastatic/recurrent nasopharyngeal carcinoma.

BACKGROUND: We investigated the survival impact and toxicity of maintenance metronomic chemotherapy in patients with metastatic/recurrent nasopharyngeal carcinoma (met/rec NPC). METHODS: Ninety-eight patients with met/rec NPC were first salvaged by IV cisplatin-based chemotherapy and showed nonprogression disease; then maintenance metronomic chemotherapy for at least 12 months was recommended. We analyzed the treatment outcome between patients who received (n = 51) and did not receive (n = 47) maintenance chemotherapy. RESULTS: Baseline patient characteristics showed no significant differences between both arms. Median overall survival for patients with and without maintenance chemotherapy was 36.0 and 12.3 months, respectively (p < 0.0001). Similarly, median progression-free survival was 24.7 and 7.3 months, respectively (p < 0.0001). Furthermore, toxicities during maintenance oral chemotherapy period were usually mild. Transient grade 3 leucopenia (9.8%), anemia (3.9%), thrombocytopenia (7.8%), and no grade 4 toxicity were observed. CONCLUSION: After IV salvage chemotherapy, maintenance oral metronomic chemotherapy significantly improved overall and progression-free survivals while demonstrating low toxicity in patients with met/rec NPC.

Nonsuicidal self-injury behaviour in a city of China and its association with family environment, media use and psychopathology.

INTRODUCTION: It is not clear whether there are differences in the risk factors for nonsuicidal self-injury (NSSI) between children and early adolescents. Clarifying this question is crucial for identifying actionable prevention strategies for NSSI in these two age groups. METHOD: The study, comprising 8611 children and early adolescents (4409 (51.2%) children, 4202 (48.8%) early adolescents), was based on the baseline data of the Chengdu Positive Child Development (CPCD) in China. NSSI behaviours, emotional and behavioural problems and family environment were assessed and obtained via self-reports and parent reports. RESULTS: Overall, 2520 (29.26%) participants reported having ever engaged in NSSI. There was a higher lifetime NSSI rate in males than in females during childhood, contrasting with higher NSSI rates in females than in males during early adolescence. Furthermore, NSSI shared similar risk factors, including major family conflict and poor relationships with caregivers, in both age groups. Specifically, in children, the risk of NSSI increased along with thought and attention problems (OR, 95% CI: 1.194, 1.106-1.288 and 1.114, 1.028-1.207, respectively), whereas in early adolescents, it increased with anxiety and depressive problems (OR, 95% CI: 1.259, 1.116-1.422). CONCLUSIONS: The findings suggested the need for difference in preventive strategies for NSSI in the two age groups. It may be more efficacious to screen for NSSI in children with thought and attention problems and in early adolescents with anxiety and depressive problems.