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BackgroundThere is a growing awareness of the heterogeneity of obstructive sleep apnoea (OSA). Clinical trials of CPAP treatment on cardiovascular protection have been mostly negative. We aimed to assess the association between polysomnographic parameters and incident major adverse cardiovascular events (MACEs), and to investigate if the CPAP effect could be better delineated among clinical subgroups.MethodsThis sleep cohort study was conducted using a clinical database and territory-wide electronic health administration data in Hong Kong. Cox regressions were used to calculate HRs. Latent class analysis was used to cluster patients with OSA according to clinical and polysomnographic features.ResultsOf 1860 eligible Chinese subjects who underwent polysomnography (2006–2013), 1544 (83%) had OSA. Over median follow-up of 8.3 years, 278 (14.9%) experienced MACEs. Apnoea–hypopnoea index (AHI) did not predict MACEs (HR: 0.95; 95% CI 0.76 to 1.17), whereas sleep time with oxygen saturation ConclusionsOSA-related TST90 and mean heart rate, but not AHI, were robust predictors of MACEs. A clinical phenotype subgroup who demonstrated beneficial effect of CPAP treatment was identified.

Background Urothelial carcinoma (UC) originates from the urinary tract and can arise from the renal pelvis, ureter, urinary bladder, and urethra. This new kind of programmed cell death, called cuproptosis, is linked to tumor advancement and microenvironment homeostasis. Nevertheless, the biological functions of cuproptosis-related genes (CRGs) in UCs are yet unknown. Methods The three Gene Expression Omnibus datasets (GEO) datasets and The Cancer Genome Atlas (TGCA) database were utilized to obtain data from 972 UC patients. R software was utilized to identify different cancer clusters and comprehensively depicted their relationships with clinical pathological characteristics and tumor microenvironment. Results Firstly, 972 UC patients underwent classification to obtain three CRG clusters based on 17 prognostic CRGs, showing significantly different prognoses, clinical features, and immune infiltration statuses (P < 0.001). Specifically, we found that cluster C displayed more like an immune-inflamed phenotype and cluster B was more consistent with the immune-desert pattern. Also, three cuproptosis gene clusters were identified according to differentially expressed genes (DEGs), displaying significantly different prognoses (P < 0.001). Secondly, we developed and validated a cuproptosis risk model and the formula we utilized was: CRG_score = (-0.0887 * HSD17B2) + (0.2014 * KDELR3) + (0.1125* EFEMP1) + (0.1118 * TMEM45A). All samples were randomly divided into the training and validation sets, and the high-risk score group was strongly correlated with poor prognosis in both sets. Besides, the two risk groups displayed significant differences in the tumor microenvironment, mutation landscape, and anti-tumor agent sensitivity. Finally, a nomogram was constructed to predict individual risk, with AUC values of 0.78, 0.79, and 0.81 for 1-, 3-, and 5-year periods, correspondingly. Conclusions This study revealed the underlying biological patterns of cuproptosis-related genes in UC. We developed a CRG risk score that could act as a practical prognostic model to predict the clinical outcome of individual UC patients.

Background: FAM83A (Family with sequence similarity 83, member A) has been found to promote tumor cell proliferation and accelerate the progression of several cancer types. However, integrated studies on the prognostic value of FAM83A and its function as an immunotherapy target in pan-cancers remain limited.Methods: Multiple online databases, including ONCOMINE, PrognoScan, Kaplan-Meier plotter, GEPIA, Lung Cancer Explorer, and TIMER, were accessed to evaluate the clinical prognostic value of FAM83A and its association with tumor-infiltrating immune cells across different cancer types.Results: Compared with normal tissues, the expression of FAM83A was higher in breast, colorectal, gastric, head and neck, and lung cancers. High FAM83A expression significantly correlated with inferior overall survival (OS) in lung cancer including lung adenocarcinoma (LUAD). In patients with LUAD, overexpressed FAM83A was negatively associated with infiltration levels of B cells and dendritic cells. In addition, the FAM83A expression level was positively associated with PD-L1, STAT1, STAT3, and JAK1 in LUAD.Conclusions: The high expression level of FAM83A was significantly correlated with a worse prognosis, which was also associated with a decreased level of infiltration of B cells and dendritic cells. FAM83A might increase the expression of PD-L1 through JAK / STAT pathway in the tumor microenvironment of lung adenocarcinoma.

Background The relationship between OSA and glucose metabolism remains controversial. This retrospective study investigated the relationship between OSA and incident type 2 diabetes (T2D) in a clinic cohort of Chinese adults in Hong Kong, and the effect of long-term CPAP treatment. Methods Data for diagnosis of incident T2D and CPAP usage were obtained from the territory-wide electronic health administration system and records of protocolized evaluation of CPAP adherence at the sleep clinic. The relationship between baseline OSA and incident T2D and the effect of CPAP therapy were examined by Cox regression models. Risk of incident T2D over the continuum of apnea-hypopnea index was examined with cubic spline analysis. Results Of 1,206 subjects with overnight sleep studies and clinical assessment in 2006 through 2013, 152 developed diabetes (median follow-up, 7.3 years). In fully adjusted models, patients with untreated moderate or severe OSA had higher risk of developing diabetes, hazard ratios 2.01 (95% CI, 1.06-3.81) and 2.62 (95% CI, 1.40-4.93) respectively, with a trend to plateau in those with severe OSA. No interaction was demonstrated between OSA and obesity. Regular CPAP use, which was attained in about one-third of subjects with moderate-severe OSA, was associated with reduction of diabetes incidence from 3.41 to 1.61 per 100 person-years, and of adjusted hazard risk to that of non-OSA. Conclusions OSA severity independently predicted incident diabetes. Regular long-term CPAP use was associated with reduced risk of incident T2D, after adjustment for various baseline metabolic risk factors and subsequent body weight change.

e14587 Background: Pneumonitis is one of the most common fatal pulmonary adverse events that stem from immune checkpoint inhibitors (ICIs). Although the combination of ICI plus chemotherapy has become the standard first-line treatment regiments for various tumors, how the risk of pneumonitis changes during the combination treatments remains unclear. We used the World Health Organization pharmacovigilance database (VigiBase) to compare the risk of pneumonitis from the combinations of ICI plus chemotherapy with ICI in other regimens, including monotherapy. Methods: This observational, retrospective, pharmacovigilance study is a disproportionality analysis based on the individual case safety reports (ICSRs) extracted from the VigiBase from 1997 to 2020. The disproportionality analysis (known as case-non-case analysis) was conducted to compare the reporting of pneumonitis from the combination of ICI plus chemotherapy with ICI in other drug regimens, including monotherapy. The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated. Results: From 1994 to 2020, A total of 93,623 ICI-associated ICSRs were reported in Vigibase, including 3,453 reports of pneumonitis (3.7%), among which 274 were associated with the combinations of ICI plus chemotherapy. The median time to event onset occurred about 2 months after therapy either in ICI without chemotherapy group or in the combination with chemotherapy group (61.5 days vs 74 days, respectively, p > 0.05). The ICI plus chemotherapy combination demonstrated a significant association with pneumonitis (ROR 1.35, 95% Cl 1.18-1.52). Among all the ICIs, anti-PD-1 antibodies combinations and anti-CTLA-4 antibodies combinations demonstrated a significant association with pneumonitis (PD-1+chemotherapy: 1.76, 95 % CI 1.52-2.05; CTLA-4+chemotherapy: 2.36, 95% Cl 1.67-3.35), while anti-PD-L1 antibodies plus chemotherapy combinations did not show similar association (ROR 0.37, 95% Cl 0.28-0.47). Conclusions: The combination of ICI plus chemotherapy is associated with higher risk of pneumonitis toxicity compared to other ICI-containing regimens (including ICI monotherapy) based on real-world data. The anti-PD-L1 plus chemotherapy combination has different pneumonitis profiles compared to anti-PD-1/CTLA-4 combinations. It suggests that a close monitoring for pneumonitis may be needed when using ICI plus chemotherapy combinations.[Table: see text]

2655 Background: Clinical trials lack direct cross-comparison in safety between immune checkpoint inhibitor (ICI) as monotherapy and in combination with chemotherapy. The adverse event of checkpoint inhibitor pneumonitis (CIP) is an important factor influencing the treatment decision making. We performed a real-world pharmacovigilance study in the US Food and Drug Administration Adverse Event Reporting System (FAERS) to determine if ICI combination therapy is superior to monotherapy for lung cancer patients in terms of CIP incidence. Methods: The database of lung cancer patients receiving ICI between 2015 and 2020 was extracted for this study. The strategy-specific durations of the pneumonitis event were compared using the Kaplan-Meier method. Reporting odds ratio (ROR), a surrogate measure in disproportionality analysis, was used to assess the signal of CIP between ICI treatment strategies. Results: A total of 27,882 lung cancer patients with reported adverse events were involved. Among them, 1763 (6.3%) CIP after ICIs therapy were identified. In general, ICI usage was associated with over-reporting frequencies of CIP, but this association was no longer significant after adjustment (ROR: 1.14, 95%CI 0.86-1.49). The median times to CIP occurred early after therapy onset, either in ICI monotherapy or in combination with chemotherapy (41 days and 37 days, log-rank p>0.05). Different reporting frequencies emerged when we further compared different ICI strategies. Combination therapy with anti-PD-1 and chemotherapy was associated with a higher CIP incidence compared with anti-PD-1 monotherapy (ROR: 1.86, 95%CI 1.37-2.51), whereas anti-PD-L1/ CTLA-4 medications had lower risks in combination with chemotherapy (ROR: 0.31, 95%CI 0.16-0.56 and ROR: 0.41, 95%CI 0.09-1.22). Subgroup analyses on those with recorded therapy duration also indicated that reports of CIP were significantly lower with combination therapy of PD-L1 and CTLA-4 (ROR: 0.52, 95%CI 0.36-0.74 and ROR: 0.22, 95%CI 0.09-0.51 respectively). Conclusions: Compared with ICI monotherapy, the combination with chemotherapy might have an acceptable risk of CIP. Anti-PD-1 medications with additional chemotherapy could increase the risk of pneumonitis, whereas the risk was lower in the combination strategy with anti-PD-L1/CTLA-4. The combination might be a better therapeutic strategy than ICI monotherapy in treating lung cancer, regarding the CIP incidence. [Table: see text]

As the main organic pollutants in wastewater, antibiotics and organic dyes are harmful to the environment and public health, and their removal is important but challenging. In this work, highly porous 3D metal-organic frameworks (MOFs) [M2 (PDAD)(H2 O)]n (PCN-124-stu; M=Cu, Zn; H4 PDAD = 5,5'-(pyridine-3,5-dicarbonyl)bis(azanediyl)diisophthalic acid) were synthesized, and PCN-124-stu(Cu) shows excellent chemical and thermal stability. PCN-124-stu(Cu) was used as a host for efficient extraction of various organic dyes, especially the large-molecule dye Coomassie brilliant blue, and fluoroquinolones from water, in comparison with five common MOFs, zeolite 13X, and activated carbon. PCN-124-stu(Cu) exhibits absolute predominance for fluoroquinolone adsorption among these microporous materials because of the H-bonds between fluoroquinolone molecules and the amide groups in the frameworks, except for MIL-100(Cr), which is a mesoporous MOF. Moreover, PCN-124-stu(Cu) could release fluoroquinolones slowly in physiological saline and retained its framework structure after four adsorption/desorption cycles. In addition, PCN-124-stu(Cu) can be used as a platform for selective adsorption of CO2 /CH4.

The relationship between OSA and glucose metabolism remains controversial. This retrospective study investigated the relationship between OSA and incident type 2 diabetes (T2D) in a clinic cohort of Chinese adults in Hong Kong, and the effect of long-term CPAP treatment.Data for diagnosis of incident T2D and CPAP usage were obtained from the territory-wide electronic health administration system and records of protocolized evaluation of CPAP adherence at the sleep clinic. The relationship between baseline OSA and incident T2D and the effect of CPAP therapy were examined by Cox regression models. Risk of incident T2D over the continuum of apnea-hypopnea index was examined with cubic spline analysis.Of 1,206 subjects with overnight sleep studies and clinical assessment in 2006 through 2013, 152 developed diabetes (median follow-up, 7.3 years). In fully adjusted models, untreated moderate or patients with severe OSA had higher risk of developing diabetes, hazard ratios 2.01 (95% CI, 1.06-3.81) and 2.62 (95% CI, 1.40-4.93) respectively, with a trend to plateau in those with severe OSA. No interaction was demonstrated between OSA and obesity. Regular CPAP use, which was attained in about one-third of subjects with moderate-severe OSA, was associated with reduction of diabetes incidence from 3.41 to 1.61 per 100 person-years, and of adjusted hazard risk to that of non-OSA.OSA severity independently predicted incident diabetes. Regular long-term CPAP use was associated with reduced risk of incident T2D, after adjustment for various baseline metabolic risk factors and subsequent body weight change.

As the main organic pollutants in wastewater, antibiotics and organic dyes are harmful to the environment and public health, and their removal is important but challenging. In this work, highly porous 3D metal-organic frameworks (MOFs) [M