Plasma indole-3-aldehyde as a novel biomarker of acute kidney injury after cardiac surgery: a reanalysis using prospective metabolomic data.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication of cardiac surgery that poses significant risks for both the development of chronic kidney diseases and mortality. Our previous study illustrated that heightened expression levels of faecal and plasma indole metabolites before the operation were associated with ischemic AKI. In this study, we aimed to validate the supposition that plasma indole-3-aldehyde (I3A) could serve as a predictive biomarker for AKI in patients undergoing cardiac surgery. METHODS: This statistical reanalysis utilized AKI metabolomic data from patients scheduled for cardiac surgery between April 2022 and July 2022 in two tertiary hospitals. Faecal and blood samples were prospectively collected before surgery within 24 h, and variables related to the preoperative, intraoperative, and postoperative periods were recorded. AKI diagnosis was based on the Kidney Disease Improving Global Outcomes criteria. RESULTS: In this study, 55 patients who underwent cardiac surgery were analyzed, and 27 of them (49.1%) developed postoperative AKI. Before surgery, these patients had significantly higher levels of faecal indole metabolites, including skatole, trans-3-indoleacrylic acid, and 5-methoxyindoleacetic acid. The plasma I3A, clinical model that considered perioperative and intraoperative variables, and their combination had area under the receiver operating characteristic curve (ROC) values of 0.79 (95% CI 0.67-0.91), 0.78 (95% CI 0.66-0.90), and 0.84 (95% CI 0.74-0.94) for predicting AKI, respectively. Furthermore, by utilizing net reclassification improvement and integrated discrimination improvement, plasma I3A showed significant improvements in risk reclassification compared to the clinical model alone. CONCLUSIONS: The dysregulation of gut microbiota metabolism in patients scheduled for cardiac surgery can result in an increase in indoles from tryptophan metabolism, which may be associated with postoperative acute kidney injury (AKI). This suggests that indoles may serve as a predictive biomarker for AKI in patients undergoing cardiac surgery.

Adjuvant Lipoic acid Injection in Sepsis treatment in China (ALIS study): protocol for a randomised, single-blind, placebo-controlled trial.

INTRODUCTION: Sepsis is a life-threatening immune disorder resulting from an dysregulated host response to infection. Adjuvant therapy is a valuable complement to sepsis treatment. Lipoic acid has shown potential in attenuating sepsis-induced immune dysfunction and organ injury in vivo and in vitro studies. However, clinical evidence of lipoic acid injection in sepsis treatment is lacking. Hence, we devised a randomised controlled trial to evaluate the efficacy and safety of lipoic acid injection in improving the prognosis of sepsis or septic shock patients. METHODS AND ANALYSIS: A total of 352 sepsis patients are planned to be recruited from intensive care units (ICUs) at eight tertiary hospitals in China for this trial. Eligible participants will undergo randomisation in a 1:1 ratio, allocating them to either the control group or the experimental group. Both groups received routine care, with the experimental group also receiving lipoic acid injection and the control group receiving placebo. The primary efficacy endpoint is 28-day all-cause mortality. The secondary efficacy endpoints are as follows: ICU and hospital mortality, ICU and hospital stay, new acute kidney injury in ICU, demand and duration of life support, Sequential Organ Failure Assessment (SOFA)/Acute Physiology and Chronic Health Evaluation II (APACHE II) and changes from baseline (ΔSOFA/ΔApache II), arterial blood lactate (LAC) and changes from baseline (ΔLAC), blood procalcitonin, high-sensitivity C-reactive protein, interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) and changes from baseline on day 1 (D1), D3, D5 and D7. Clinical safety will be assessed through analysis of adverse events. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Maoming People's Hospital (approval no. PJ2020MI-019-01). Informed consent will be obtained from the participants or representatives. The findings will be disseminated through academic conferences or journal publications. TRIAL REGISTRATION: ChiCTR2000039023.

Ventilator-associated pneumonia prevention in the Intensive care unit using Postpyloric tube feeding in China (VIP study): study protocol for a randomized controlled trial.

BACKGROUND: Ventilator-associated pneumonia is a challenge in critical care and is associated with high mortality and morbidity. Although some consensuses on preventing ventilator-associated pneumonia are reached, it is still somewhat controversial. Meta-analysis has shown that postpyloric tube feeding may reduce the incidences of ventilator-associated pneumonia, which still desires high-quality evidence. This trial aims to evaluate the efficacy and safety profiles of postpyloric tube feeding versus gastric tube feeding. METHODS/DESIGN: In this multicenter, open-label, randomized controlled trial, we will recruit 924 subjects expected to receive mechanical ventilation for no less than 48 h. Subjects on mechanical ventilation will be randomized (1:1) to receive postpyloric or gastric tube feeding and routine preventive measures simultaneously. The primary outcome is the proportion of patients with at least one ventilator-associated pneumonia episode. Adverse events and serious adverse events will be observed closely. DISCUSSION: The VIP study is a large-sample-sized, multicenter, open-label, randomized, parallel-group, controlled trial of postpyloric tube feeding in China and is well-designed based on previous studies. The results of this trial may help to provide evidence-based recommendations for the prevention of ventilator-associated pneumonia. TRIAL REGISTRATION: Chictr.org.cn ChiCTR2100051593 . Registered on 28 September 2021.

Natural recovery from fire disturbance is more favorable than assisted recovery for the restoration of soil nematode-trapping fungi.

A fire is usually considered a severe disturbance factor in the environment. Globally, rising temperatures and increasing human activities have intensified the severity and frequency of fire incidents, and research on post-fire recovery has inevitably become an important focus for ecologists. In terms of the restoration of burned areas, there are usually two primary approaches: natural recovery and assisted recovery. However, very few relevant studies have systematically compared these recovery alternatives, suggesting which one is more favorable to the overall restoration of an ecosystem, especially to the soil microbes that function as indispensable components of ecosystems. In this study, the restoration of soil nematode-trapping fungi (NTF) in natural and assisted recovery environments was compared. The results showed that although the NTF community structures differed among the sample sites, the counts and diversity of the NTF communities in the upper and lower soil layers in the natural recovery area were higher than those in the assisted recovery and unburned control areas. These findings suggest that artificial efforts to help ecosystem recovery after fire negatively affect the speed and quality of soil NTF community recovery. Instead, natural recovery appears to be a more suitable land management choice after fire disturbance.

Impacts of HIV-1 Subtype Diversity on Long-Term Clinical Outcomes in Antiretroviral Therapy in Guangxi, China.

BACKGROUND: Comprehensively estimating the impacts of HIV-1 subtype diversity on long-term clinical outcomes during antiretroviral therapy (ART) can help inform program recommendations. METHODS: The HIV-1 sequence data and clinical records of 5950 patients from all 14 prefectures in Guangxi, China, during 2008-2020 were included. Evolutional trends of CD4+ T-lymphocyte count and viral load were explored, and the effects of HIV-1 subtypes on clinical outcomes were estimated by the Cox proportional hazards model. The polymorphisms involved in drug resistance mutation were analyzed. RESULTS: Compared with patients with CRF07_BC, patients with CRF01_AE and CRF08_BC showed poor immunologic and virologic responses to antiretroviral therapy. Although the median expected time from ART initiation to virologic suppression for all patients was approximately 12 months, patients with CRF01_AE and CRF08_BC had a long time to achieve immune recovery and a short time to occur immunologic failure, compared with patients with CRF07_BC. Adjusted analysis showed that both CRF01_AE and CRF08_BC were the negative factors in immune recovery and long-term mortality. In addition, CRF08_BC was a negative factor in virologic suppression and a risk factor of virologic failure. This poor virologic response might result from the high prevalence of drug resistance mutation in CRF08_BC. CONCLUSIONS: Compared with patients with CRF07_BC, patients with CRF01_AE could benefit more from immediate ART, and patients with CRF08_BC are more suitable for PI-based regimens. These data emphasize the importance of routine HIV-1 genotyping before ART, immediate ART, and personalized ART regimens to improve the prognosis for patients undergoing ART.

A Prognostic Model to Assess Long-Term Survival of Patients on Antiretroviral Therapy: A 15-Year Retrospective Cohort Study in Southwestern China.

BACKGROUND: Because there is no assessment tool for survival of people with human immunodeficiency virus (PWH) who received antiretroviral therapy (ART) in rural southwestern China, we aimed to formulate and validate a simple-to-use model to predict long-term overall survival at the initiation of ART. METHODS: In total, 36 268 eligible participants registered in the Guangxi autonomous region between December 2003 and December 2018 were enrolled and randomized into development and validation cohorts. Predictive variables were determined based on Cox hazard models and specialists' advice. Discrimination, calibration, and clinical utility were measured, respectively. RESULTS: The prognostic combined 14 variables: sex, age, marital status, infectious route, opportunistic infection, acquired immunodeficiency syndrome (AIDS)-related symptoms, body mass index, CD4+ T lymphocyte count, white blood cell, platelet, hemoglobin, serum creatinine, aspartate transaminase, and total bilirubin. Age, aspartate transaminase, and serum creatinine were assigned higher risk scores than that of CD4+ T lymphocytopenia count and having opportunistic infections or AIDS-related symptoms. At 3 time points (1, 3, and 5 years), the area under the curve ranged from 0.75 to 0.81 and the Brier scores ranged from 0.03 to 0.07. The decision curve analysis showed an acceptable clinical net benefit. CONCLUSIONS: The prognostic model incorporating routine baseline data can provide a useful tool for early risk appraisal and treatment management in ART in rural southwestern China. Moreover, our study underscores the role of non-AIDS-defining events in long-term survival in ART.

HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China.

BACKGROUND: The widespread use of antiretroviral therapy (ART) has resulted in the development of transmitted drug resistance (TDR), which reduces ART efficacy. We explored TDR prevalence and its associated risk factors in newly diagnosed individuals in Guangxi. METHODS: We enrolled 1324 participants who were newly diagnosed with HIV-1 and had not received ART at voluntary counselling and testing centres (VCT) in Guangxi, China, who had not received ART. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 pol sequences. We analysed the association of demographic and virological factors with TDR. RESULTS: In total, 1151 sequences were sequenced successfully, of which 83 (7.21%) showed evidence of TDR. Multivariate logistic regression analysis revealed that there was significant difference between the prevalence of TDR and unmarried status (adjusted odds ratio (aOR) = 2.41, 95% CI: 1.23-4.71), and CRF08_BC subtype (aOR = 2.03, 95% CI: 1.13-3.64). Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. We identified a total of 119 HIV transmission clusters (n = 585, 50.8%), of which 18 (15.1%) clusters showed evidence of TDR (36, 41.86%). Three clusters were identified that included drug-resistant individuals having a transmission relationship with each other. The following parameters were associated with TDR transmission risk: Unmarried status, educational level of junior high school or below, and CRF08_BC subtype may be a risk of the transmission of TDR. CONCLUSIONS: Our findings indicated that moderate TDR prevalence and highlighted the importance of continuous TDR monitoring and designing of strategies for TDR mitigation.

Patterns and risk of HIV-1 transmission network among men who have sex with men in Guangxi, China.

The prevalence of HIV-1 in Guangxi is very high, and the rate of HIV-1 infection among men who have sex with men (MSM) has been increasing. Therefore, it is necessary to explore the patterns and risk factors of HIV transmission in Guangxi. For this purpose, individuals diagnosed with HIV-1 during 2013-2018 in Guangxi were recruited. Phylogenetic relationship, transmission clusters, and genotypic drug resistance analyses were performed based on HIV-1 pol sequences. Related factors were analysed to assess for their association with HIV-1 transmission. CRF07_BC (50.4%) and CRF01_AE (33.4%) were found to be the predominant subtypes. The analysed 1633 sequences (50.15%, Guangxi; 49.85%, other provinces) were segregated into 80 clusters (size per cluster, 2-704). We found that 75.3% of the individuals were in three clusters (size Ëƒ 100), and 73.8% were high-risk spreaders (links ≥ 4). Infection time, marital status, and subtype were significantly associated with HIV-1 transmission. Additionally, 80.2% of recent infections were linked to long-term infections, and 46.2% were linked to other provinces. A low level of transmitted drug resistance was detected (4.8%). Our findings indicated superclusters and high-risk HIV-1 spreaders among the MSM in Guangxi. Effective strategies blocking the route of transmission should be developed.

Effects of HIV-1 genotype on baseline CD4+ cell count and mortality before and after antiretroviral therapy.

To assess whether human immunodeficiency virus type 1 (HIV-1) genotype influences baseline CD4+ T lymphocyte (CD4+) cell count and mortality of patients. The study was conducted from 2014 to 2019 in Guangxi, China, and included 2845 newly diagnosed HIV patients. We used a median regression model to compare CD4+ cell counts in patients newly diagnosed with different HIV-1 genotypes, and a Cox regression model to analyze the associations between HIV-1 genotypes and mortality before and after antiretroviral treatment (ART). In newly diagnosed HIV patients, the baseline CD4+ cell counts of patients with CRF01_AE were significantly lower than those of patients with CRF07_BC, CRF08_BC, and other genotypes. Compared with CRF01_AE, patients infected with CRF07_BC (hazard ratio, 0.55; 95% CI 0.36-0.85), CRF08_BC (hazard ratio, 0.67; 95% CI 0.52-0.85), or other genotypes (hazard ratio, 0.52; 95% CI 0.29-0.94) had significantly lower mortality rates before ART. There were no significant associations between different HIV-1 genotypes and mortality after ART. HIV-1 genotype significantly influences baseline CD4+ cell count and mortality before ART in newly diagnosed HIV patients. We find no significant difference in the outcome of death after ART in patients with different HIV-1 genotypes.

Author Correction: HIV-1 Transmissions Among Recently Infected Individuals in Southwest China are Predominantly Derived from Circulating Local Strains.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

HIV-1 Transmissions Among Recently Infected Individuals in Southwest China are Predominantly Derived from Circulating Local Strains.

Although the Guangxi region accounts for 10% of all HIV-1 cases new reported in 2011 in China, the sources of the transmitted HIV-1 strains are virtually unknown. To determine the extent to which recent HIV infections were derived from already circulating local strains as opposed to recently introduced strains, we performed a cross-sectional molecular epidemiological investigation of recent infections across Guangxi during 2012-2013. HIV-1 nucleotide sequences were amplified and sequenced. Phylogenetic analyses of pol gene regions were used to determine HIV-1 transmission source strains. Based on 229 sequences generated, the subtype/CRF distribution was as follows: CRF01_AE (61.1%), CRF07_BC (18.8%), CRF08_BC (16.6%), CRF55_01B (3.1%), and subtype B' (0.4%). In total, 213 of 229 (93.0%) sequenced transmission strains were derived from already-circulating local strains. Multivariate logistic regression analysis showed that only an age of 18-25 years was significantly associated with transmission from outside Guangxi (compared to >25 years, AOR: 5.15, 95% CI: 1.18-22.48, p < 0.01). This is the first study to use a Bayesian discrete phylogeographic approach to analyze transmission source strains in China. Our results provide useful data for designing evidence-based prevention strategies and methods for combating the rapid spread of sexually transmitted HIV in Guangxi.

Trends in nasopharyngeal carcinoma mortality in China, 1973-2005.

Nasopharyngeal carcinoma (NPC) is a disease with distinct ethnic and geographic distribution. The incidence of NPC in Chinese residing in Asia has declined over the last few decades, but NPC mortality trends in the entire Chinese population over time have not been systematically evaluated. In this study, we examined NPC mortality at the national level in China between 1973-2005. Mortality rates were derived from the databases of national retrospective surveys on cancer mortality conducted in the periods of 1973-1975, 1990-1992, and 2004-2005, respectively. NPC was classified according to the International classification of diseases. Age-adjusted mortality rates were calculated by direct standardization according to the world standard population. Trends in rates were evaluated by age, gender, geographic areas, and socioeconomic status. From 1973 to 2005, there was a general trend of decrease in NPC mortality in China, with higher rates in the south on a downward trend in the north. The age-standardized NPC mortality rates were 2.60 per 100,000 in 1973-1975, 1.94 per 100,000 in 1990-1992, and 1.30 per 100,000 in 2004-2005, respectively. The trend was similar in both men and women, in both urban and rural areas, but the declining rates in females were more remarkable than in males. The mortality rates were higher for the age groups above 50 years than those less than 50 years of age, both showing downward trend over 30-year period. In summary, the overall NPC mortality has consistently decreased in China over the past three decades, particularly in women and in old adults.