Infections in patients with chronic kidney disease : patterns, outcomes and the role of vitamin D for future prevention

Background: Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. Patients with CKD are at high risk of infections. Frequent episodes of infections with greater use of antibiotics might put this population at risk of infections caused by resistant organisms. Thus, infection issues in patients with CKD could be related to another public health problem - antibiotic resistance. Aim: To investigate the antibiotic resistant patterns of pathogens responsible for infections, ascertain short-term and long-term patient outcomes during and after hospitalizations with infections and explore the role of vitamin D for infection prevention in patients with CKD. Methods: The thesis consists of two observational studies (Paper I & II), one cohort study (Paper III) and one systematic review and meta-analysis (Paper IV). Paper I, II & III explored the association between kidney function (defined as estimated glomerular filtration rate, eGFR) and various outcomes. These outcomes included microbial pattern (Paper I), prevalence of infections with multi-drug resistant organisms (MDROs) in the first positive microbial cultures (Paper I), intensive care unit admission (Paper II), length of hospital stay (Paper II), medical expense (Paper II), and mortality (Paper II & III). These were assessed in patients hospitalized with infections, using electronic medical records from four hospitals from 2012 to 2015 in China. Paper IV obtained data from existing literature to explore the association of infections with vitamin D status or use of vitamin D in patients treated with long-term dialysis. Results: In adult patients hospitalized with infections, the proportion of Gram-negative bacteria decreased while the proportion of Gram-positive bacteria increased across eGFR strata. Compared with the reference eGFR, lower eGFR was associated with: higher odds of infections by MDROs (19% and 41% higher in those with eGFR between 30-59 ml/min/1.73 m2 and eGFR <30 ml/min/1.73 m2, respectively) (Paper I); more than twofold higher adjusted odds of ICU admission, longer median length of hospital stay (P< 0.001), inferred 20.0% higher costs in those with eGFR< 60 ml/min/1.73 m2 (P< 0.001) (Paper II); progressively increased risks of cardiovascular mortality (subdistribution hazard ratio [SHR] 2.15 for eGFR 30-59 mL/min/1.73m2; SHR 3.19 for eGFR<30 mL/min/1.73m2) (Paper III). In the systematic review of vitamin D and infections in patients treated with long-term dialysis, the risk of composite infections was 39% lower in those with high/normal levels of 25-hydroxy vitamin D than that in those with low levels. Compared to those who did not use vitamin D, the pooled adjusted risk of composite infection was 41% lower in those who used vitamin D (Paper IV). Conclusions: CKD patients hospitalized with infections have a higher risk of infections by MDROs, poorer in-hospital outcomes resulting in higher medical costs and increased risk of cardiovascular mortality in the long-run. Use of vitamin D to achieve high/normal serum levels of 25(OH)-vitamin D might help lowering the risk of infections in maintenance dialysis patients. Further research is needed to investigate the potential role of vitamin D therapy in infection prevention among non-dialysis dependent CKD patients

Fermi Bubbles Inflated by Winds Launched from the Hot Accretion Flow in Sgr A*

A pair of giant gamma-ray bubbles have been revealed by the {\it Fermi} LAT. In this paper we investigate their formation mechanism. Observations have indicated that the activity of the supermassive black hole located at the Galactic center, Sgr A*, was much stronger than the present time. Specifically, one possibility is that while Sgr A* was also in the hot accretion regime, the accretion rate should be $10^3-10^4$ times higher during the past $\sim 10^7$ yr. On the other hand, recent MHD numerical simulations of hot accretion flows have unambiguously shown the existence of strong winds and obtained their properties. Based on these knowledge, by performing three-dimensional hydrodynamical simulations, we show in this paper that the Fermi bubbles could be inflated by winds launched from the ``past' hot accretion flow in Sgr A*. In our model, the active phase of Sgr A* is required to last for about 10 million years and it was quenched no more than 0.2 million years ago. The Central Molecular Zone (CMZ) is included and it collimates the wind orientation towards the Galactic poles. Viscosity suppresses the Rayleigh-Taylor and Kelvin-Helmholtz instabilities and results in the smoothness of the bubble edge. The main observational features of the bubbles can be well explained. Specifically, the {\it ROSAT} X-ray features are interpreted by the shocked interstellar medium and the interaction region between winds and CMZ gas. The thermal pressure and temperature obtained in our model are in good consistency with the recent {\it Suzaku} observations.Comment: 12 pages,8 figures, Accepted by Ap

Clinical applications of radiomics in non-small cell lung cancer patients with immune checkpoint inhibitor-related pneumonitis

Immune checkpoint inhibitors (ICIs) modulate the body’s immune function to treat tumors but may also induce pneumonitis. Immune checkpoint inhibitor-related pneumonitis (ICIP) is a serious immune-related adverse event (irAE). Immunotherapy is currently approved as a first-line treatment for non-small cell lung cancer (NSCLC), and the incidence of ICIP in NSCLC patients can be as high as 5%-19% in clinical practice. ICIP can be severe enough to lead to the death of NSCLC patients, but there is a lack of a gold standard for the diagnosis of ICIP. Radiomics is a method that uses computational techniques to analyze medical images (e.g., CT, MRI, PET) and extract important features from them, which can be used to solve classification and regression problems in the clinic. Radiomics has been applied to predict and identify ICIP in NSCLC patients in the hope of transforming clinical qualitative problems into quantitative ones, thus improving the diagnosis and treatment of ICIP. In this review, we summarize the pathogenesis of ICIP and the process of radiomics feature extraction, review the clinical application of radiomics in ICIP of NSCLC patients, and discuss its future application prospects

Modifiable lifestyle factors for primary prevention of chronic kidney disease: a systematic review and meta-analysis

BACKGROUND: Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. METHODS: To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m(2)). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria). RESULTS: We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding. CONCLUSIONS: These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice

Activated Amorphous Carbon With High-Porosity Derived From Camellia Pollen Grains as Anode Materials for Lithium/Sodium Ion Batteries

Carbonaceous anode materials are commonly utilized in the energy storage systems, while their unsatisfied electrochemical performances hardly meet the increasing requirements for advanced anode materials. Here, activated amorphous carbon (AAC) is synthesized by carbonizing renewable camellia pollen grains with naturally hierarchical structure, which not only maintains abundant micro- and mesopores with surprising specific surface area (660 m2 g−1), but also enlarges the interlayer spacing from 0.352 to 0.4 nm, effectively facilitating ions transport, intercalation, and adsorption. Benefiting from such unique characteristic, AAC exhibits 691.7 mAh g−1 after 1200 cycles at 2 A g−1, and achieves 459.7, 335.4, 288.7, 251.7, and 213.5 mAh g−1 at 0.1, 0.5, 1, 2, 5 A g−1 in rate response for lithium-ion batteries (LIBs). Additionally, reversible capacities of 324.8, 321.6, 312.1, 298.9, 282.3, 272.4 mAh g−1 at various rates of 0.1, 0.2, 0.5, 1, 2, 5 A g−1 are preserved for sodium-ion batteries (SIBs). The results reveal that the AAC anode derived from camellia pollen grains can display excellent cyclic life and superior rate performances, endowing the infinite potential to extend its applications in LIBs and SIBs

Kidney disease and mortality in patients with respiratory tract infections: a systematic review and meta-analysis.

BACKGROUND: Respiratory tract infections (RTIs) are a common reason for people to seek medical care. RTIs are associated with high short-term mortality. Inconsistent evidence exists in the association between the presence of kidney disease and the risk of death in patient with RTIs. METHODS: We searched the PubMed, Cochrane Library and Embase databases from inception through April 2019 for cohort and case-control studies investigating the presence of kidney disease (defined as medical diagnosis of kidney disease, reduced estimated glomerular filtration rate or creatinine clearance, elevated serum creatinine and proteinuria) on mortality in adults with RTIs in different settings including community, inpatient and intensive care units. We assessed the quality of the included studies using Cochrane Collaboration's tool and conducted a meta-analysis on the relative risk (RR) of death. RESULTS: Of 5362 records identified, 18 studies involving 16 676 participants met the inclusion criteria, with 15 studies investigating pneumonia and 3 studies exploring influenza. The risk of bias in the available evidence was moderate. Most [17/18 (94.5%)] of studies reported positive associations of underlying chronic kidney disease with mortality. The pooled adjusted risk for all-cause mortality in patients with RTIs almost doubled [RR 1.96 (95% confidence interval 1.48-2.59)] in patients with kidney disease. Associations were consistent across different timings of kidney disease assessment and provenances of RTIs (community-acquired or healthcare-associated). CONCLUSIONS: The presence of kidney disease is associated with higher mortality among people with RTIs, especially in those with pneumonia. The presence of kidney disease might be taken into account when considering admission for patients who present with RTIs

Effectiveness and safety of pneumococcal vaccines used alone or combined with influenza vaccination in dialysis patients: A systematic review and meta-analysis.

BACKGROUND: A lower conversion vaccination rate and a more rapid decline in antibody titers over time in dialysis patients raise concerns about the effectiveness of pneumococcal vaccination (PV) in this population, which has not been systematically reviewed. METHODS: We searched PubMed, Cochrane Library, Embase and three Chinese databases from inception until February 29th, 2020 for interventional, cohort and case-control studies evaluating PV alone or combined with influenza vaccination (IV) on outcomes (all-cause mortality, pneumonia, cardiovascular events, antibody response and safety). Independent reviewers completed citation screening, data extraction, risk assessment, meta-analysis, and GRADE rating of the quality of evidence. RESULTS: Five cohort studies and one quasirandomized control trial enrolling 394,299 dialysis patients with high to moderate quality were included. Compared with unvaccinated individuals, those receiving PV had lower risk of all-cause mortality [Adjusted relative risk (RR) 0.73, 95% CI 0.67-0.79, I2 = 31.1%, GRADE low certainty] and cardiovascular events (adjusted RR 0.80, 95% CI 0.69-0.93, I2 = 47.2%, GRADE low certainty) without serious adverse effect reported. Compared with no vaccination, lower all-cause mortality was observed in those receiving PV combined with IV (Adjusted RR 0.71, 95%CI 0.67-0.75, I2 = 63.3%), PV alone (Adjusted RR 0.86, 95% CI 0.78-0.94,I2 = 0%], and IV alone (Adjusted RR 0.76, 95% CI 0.73-0.79, I2 = 0%]. There was no difference between pneumococcal vaccinated patients vs non-vaccinated patients with respect to pneumonia. Immune response to pneumococcal conjugate vaccine-13 was weaker in polysaccharide pneumococcal vaccine-23-pre-vaccinated compared with vaccine-naive patients. CONCLUSIONS: The use of pneumococcal vaccine especially combined with influenza vaccination is associated with lower risks of all-cause mortality but may be affected by residual confounding/healthy vaccinee bias

FECTS: A Facial Emotion Cognition and Training System for Chinese Children with Autism Spectrum Disorder

Traditional training methods such as card teaching, assistive technologies (e.g., augmented reality/virtual reality games and smartphone apps), DVDs, human-computer interactions, and human-robot interactions are widely applied in autistic rehabilitation training in recent years. In this article, we propose a novel framework for human-computer/robot interaction and introduce a preliminary intervention study for improving the emotion recognition of Chinese children with an autism spectrum disorder. The core of the framework is the Facial Emotion Cognition and Training System (FECTS, including six tasks to train children with ASD to match, infer, and imitate the facial expressions of happiness, sadness, fear, and anger) based on Simon Baron-Cohen's E-S (empathizing-systemizing) theory. Our system may be implemented on PCs, smartphones, mobile devices such as PADs, and robots. The training record (e.g., a tracked record of emotion imitation) of the Chinese autistic children interacting with the device implemented using our FECTS will be uploaded and stored in the database of a cloud-based evaluation system. Therapists and parents can access the analysis of the emotion learning progress of these autistic children using the cloud-based evaluation system. Deep-learning algorithms of facial expressions recognition and attention analysis will be deployed in the back end (e.g., devices such as a PC, a robotic system, or a cloud system) implementing our FECTS, which can perform real-time tracking of the imitation quality and attention of the autistic children during the expression imitation phase. In this preliminary clinical study, a total of 10 Chinese autistic children aged 3-8 are recruited, and each of them received a single 20-minute training session every day for four consecutive days. Our preliminary results validated the feasibility of the developed FECTS and the effectiveness of our algorithms based on Chinese children with an autism spectrum disorder. To verify that our FECTS can be further adapted to children from other countries, children with different cultural/sociological/linguistic contexts should be recruited in future studies