Cardiovascular outcomes in obstructive sleep apnoea and implications of clinical phenotyping on effect of CPAP treatment.

BACKGROUND: There 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. METHODS: This 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. RESULTS: Of 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 <90% (TST90) (HR: 1.41; 95% CI 1.10 to 1.81) was an independent predictor of MACEs, as were wake and nocturnal heart rate. In moderate-severe OSA (n=1108) who were indicated for CPAP treatment, regular CPAP was not associated with reduction of incident MACEs. Further cluster analysis identified a subgroup (n=333) who was younger, more obese, had more severe OSA (higher AHI and TST90) and more cardiovascular risks, in whom regular CPAP was associated with a lower risk of MACEs (HR:0.49, 95% CI 0.25 to 0.95). CONCLUSIONS: OSA-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.

Gut-derived fungemia due to Kodamaea ohmeri combined with invasive pulmonary aspergillosis: a case report.

BACKGROUND: Kodamaea ohmeri is a rare pathogen with high mortality and is found among blood samples in a considerable proportion; however, gastrointestinal infection of K. ohmeri is extremely rare. Invasive pulmonary aspergillosis is also an uncommon fungal; these two fungal infections reported concomitantly are unprecedented. CASE PRESENTATION: We described a case of a 37-year-old male who got infected with K. ohmeri and invasive pulmonary aspergillosis. We used the mass spectrometry and histopathology to identify these two fungal infections separately. For the treatment of K. ohmeri, we chose caspofungin. As for invasive pulmonary aspergillosis, we used voriconazole, amphotericin B, and then surgery. The patient was treated successfully through the collaboration of multiple disciplines. CONCLUSIONS: We speculate that the destruction of the intestinal mucosa barrier can make the intestine one of the ways for certain fungi to infect the human body.

An Exceptionally Water Stable Metal-Organic Framework with Amide-Functionalized Cages: Selective CO2 /CH4 Uptake and Removal of Antibiotics and Dyes from Water.

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.

Prediction and related genes of cancer distant metastasis based on deep learning.

Cancer metastasis is one of the main causes of cancer progression and difficulty in treatment. Genes play a key role in the process of cancer metastasis, as they can influence tumor cell invasiveness, migration ability and fitness. At the same time, there is heterogeneity in the organs of cancer metastasis. Breast cancer, prostate cancer, etc. tend to metastasize in the bone. Previous studies have pointed out that the occurrence of metastasis is closely related to which tissue is transferred to and genes. In this paper, we identified genes associated with cancer metastasis to different tissues based on LASSO and Pearson correlation coefficients. In total, we identified 45 genes associated with bone metastases, 89 genes associated with lung metastases, and 86 genes associated with liver metastases. Through the expression of these genes, we propose a CNN-based model to predict the occurrence of metastasis. We call this method MDCNN, which introduces a modulation mechanism that allows the weights of convolution kernels to be adjusted at different positions and feature maps, thereby adaptively changing the convolution operation at different positions. Experiments have proved that MDCNN has achieved satisfactory prediction accuracy in bone metastasis, lung metastasis and liver metastasis, and is better than other 4 methods of the same kind. We performed enrichment analysis and immune infiltration analysis on bone metastasis-related genes, and found multiple pathways and GO terms related to bone metastasis, and found that the abundance of macrophages and monocytes was the highest in patients with bone metastasis.

Comprehensive Collection of Whole-Slide Images and Genomic Profiles for Patients with Bladder Cancer.

Bladder cancer is one of the leading causes of cancer-related mortality in the urinary system. Understanding genomic information is important in the treatment and prognosis of bladder cancer, but the current method used to identify mutations is time-consuming and labor-intensive. There are now many novel and convenient ways to predict cancerous genomics from pathological slides. However, the publicly available datasets are limited, especially for Asian populations. In this study, we developed a dataset consisting of 75 Asian cases of bladder cancers and 112 Whole-Slide Images with one to two images obtained for each patient. This dataset provides information on the most frequently and clinically significant mutated genes derived by whole-exome sequencing in these patients. This dataset will facilitate exploration and development of novel diagnostic and therapeutic technologies for bladder cancer.

FGFR3 mutation characterization identifies prognostic and immune-related gene signatures in bladder cancer.

BACKGROUND: Immunotherapy and FGFR3-targeted therapy play an important role in the management of locally advanced and metastatic bladder cancer (BLCA). Previous studies indicated that FGFR3 mutation (mFGFR3) may be involved in the alterations of immune infiltration, which may affect the priority or combination of these two treatment regimes. However, the specific impact of mFGFR3 on the immunity and how FGFR3 regulates the immune response in BLCA to affect prognosis remain unclear. In this study, we aimed to elucidate the immune landscape associated with mFGFR3 status in BLCA, screen immune-related gene signatures with prognostic value, and construct and validate a prognostic model. METHODS: ESTIMATE and TIMER were used to assess the immune infiltration within tumors in the TCGA BLCA cohort based on transcriptome data. Further, the mFGFR3 status and mRNA expression profiles were analyzed to identify immune-related genes that were differentially expressed between patients with BLCA with wild-type FGFR3 or mFGFR3 in the TCGA training cohort. An FGFR3-related immune prognostic score (FIPS) model was established in the TCGA training cohort. Furthermore, we validated the prognostic value of FIPS with microarray data in the GEO database and tissue microarray from our center. Multiple fluorescence immunohistochemical analysis was performed to confirm the relationship between FIPS and immune infiltration. RESULTS: mFGFR3 resulted in differential immunity in BLCA. In total, 359 immune-related biological processes were enriched in the wild-type FGFR3 group, whereas none were enriched in the mFGFR3 group. FIPS could effectively distinguish high-risk patients with poor prognosis from low-risk patients. The high-risk group was characterized by a higher abundance of neutrophils; macrophages; and follicular helper, CD4, and CD8 T-cells than the low-risk group. In addition, the high-risk group exhibited higher expression of PD-L1, PD-1, CTLA-4, LAG-3, and TIM-3 than the low-risk group, indicating an immune-infiltrated but functionally suppressed immune microenvironment. Furthermore, patients in the high-risk group exhibited a lower mutation rate of FGFR3 than those in the low-risk group. CONCLUSIONS: FIPS effectively predicted survival in BLCA. Patients with different FIPS exhibited diverse immune infiltration and mFGFR3 status. FIPS might be a promising tool for selecting targeted therapy and immunotherapy for patients with BLCA.

Intravesical Recurrence After Radical Nephroureterectomy of Upper Urinary Tract Urothelial Carcinoma: A Large Population-Based Investigation of Clinicopathologic Characteristics and Survival Outcomes.

Background: Of patients with upper urinary tract urothelial carcinoma (UTUC), 22-47% developed bladder recurrence after radical nephroureterectomy. Furthermore, the effect of surgery for UTUC-bladder cancer (BC) has not been well validated. The aim of this study was to assess the impact of standard primary BC surgical strategy on survival of patients diagnosed with UTUC-BC. Patients and Methods: A total of 676 UTUC-BC patients and 197,753 primary BC patients diagnosed from 2004 to 2016, were identified based on the SEER database. The Kaplan-Meier method and the Fine and Gray competing risks analysis were performed to assess overall survival (OS) and cancer-specific mortality (CSM). Multivariate Cox regression model and competing risks regression model were used to identify independent risk factors. Propensity score matching (PSM) was also performed to adjust potential confounding factors. Results: The baseline characteristics and survival outcomes of the two BC patient cohorts are quite different. For UTUC-BC patients, no significant difference in OS (NMIBC: p = 0.88; MIBC: p = 0.98) or cumulative incidence of CSM (NMIBC: p = 0.12; MIBC: p = 0.96) were noted for various surgical procedures. Local tumor treatment and partial cystectomy for UTUC-NMIBC patients produced lower 1-year (6.1%) and 3-year CSM (16.2%). Radical cystectomy for UTUC-MIBC patients produced lower 1-year (11.8%) but higher 3-year CSM (62.7%). After PSM for covariates, UTUC-BC patients still had a worse prognosis after surgery compared with primary BC patients. Based on regression models, older age, advanced T stage, N positive disease, M positive disease, and shorter interval between UTUC and BC were identified as independent risk factors for UTUC-BC patients. Conclusion: Standard primary BC surgical strategy did not provide significant survival benefit for UTUC-BC patients. Compared with primary BC patients, UTUC-BC patients had a worse prognosis after surgery, suggesting that current primary BC surgical guidelines are not entirely appropriate for UTUC-BC patients. Our findings underscore the continued importance and need for better prognosis and improved guidelines for management of UTUC-BC patients.

Prognostic value of primary tumor surgery in seminoma patients with distant metastasis at diagnosis: a population-based study.

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (<60 years) may benefit from primary tumor surgery. In conclusion, our findings indicate that primary tumor surgery is correlated with improved survival in patients with seminoma and distant metastasis. Furthermore, primary tumor surgery is an independent prognostic indicator for patients with seminoma and distant metastasis.

Incident Type 2 Diabetes in OSA and Effect of CPAP Treatment: A Retrospective Clinic Cohort Study.

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, 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. 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.