A Machine learning model for predicting sepsis based on an optimized assay for microbial cell-free DNA sequencing.

OBJECTIVE: To integrate an enhanced molecular diagnostic technique to develop and validate a machine-learning model for diagnosing sepsis. METHODS: We prospectively enrolled patients suspected of sepsis from August 2021 to August 2023. Various feature selection algorithms and machine learning models were used to develop the model. The best classifier was selected using 5-fold cross validation set and then was applied to assess the performance of the model in the testing set. Additionally, we employed the Shapley Additive exPlanations (SHAP) method to illustrate the effects of the features. RESULTS: We established an optimized mNGS assay and proposed using the copies of microbe-specific cell-free DNA per milliliter of plasma (CPM) as the detection signal to evaluate the real burden, with strong precision and high accuracy. In total, 237 patients were eligible for participation, which were randomly assigned to either the training set (70 %, n = 165) or the testing set (30 %, n = 72). The random forest classifier achieved accuracy, AUC and F1 scores of 0.830, 0.918 and 0.856, respectively, outperforming other machine learning models in the training set. Our model demonstrated clinical interpretability and achieved good prediction performance in differentiating between bacterial sepsis and non-sepsis, with an AUC value of 0.85 and an average precision of 0.91 in the testing set. Based on the SHAP value, the top nine features of the model were PCT, CPM, CRP, ALB, SBPmin, RRmax, CREA, PLT and HRmax. CONCLUSION: We demonstrated the potential of machine-learning approaches for predicting bacterial sepsis based on optimized mcfDNA sequencing assay accurately.

Cardiovascular health, sleeping duration, and risk of mortality in current and former smokers.

BACKGROUND AND AIMS: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with all-cause mortality among former and current smokers compared with never smokers. METHODS AND RESULTS: A total of 378,147 participants [mean age (SD) years: 56.3 (8.1); 47.2 % men] were included from the UK Biobank cohort. The ICVHMs were combined Life's simple 7 from the American Heart Association and sleep duration time. The association was explored using COX regression models. During a median follow-up of 13.3 years, we documented 24,594 deaths. Compared with never smokers, among former smokers, the multivariable-adjusted hazard ratio (HR) for all-cause mortality was 1.82 (95%CI 1.71-1.92) for participants who had ≤2 ICVHMs and 1.03 (0.97-1.10) for participants who had ≥6 ICVHMs; among current smokers, the HRs for mortality were 2.74 (2.60-2.89) and 2.18 (1.78-2.67). The phenomenon was more pronounced among participants younger than 60 years [HR (95%CI), 1.82 (1.71-1.95) for ≤2 ICVHMs vs 1.04 (0.96-1.12) for ≥6 ICVHMs with age ≥60 years and 1.83 (1.62-2.06) vs 0.98 (0.88-1.11) with age <60 years among former smokers; 2.66 (2.49-2.85) vs 2.44 (1.84-3.24) with age ≥60 years and 2.85 (2.62-3.10) vs 1.96 (1.47-2.61) with age <60 years among current smokers]. In addition, the HR for mortality of each 1-number increment in ICVHMs was 0.87 (0.86-0.89) among former smokers and 0.91 (0.89-0.94) among current smokers. CONCLUSION: Our findings indicated the importance of adherence to have more ICVHMs in the mortality risk among former smokers, and priority of smoking cessation in current smokers. IMPLICATIONS: Studies have found that former smokers still have higher risks of lung cancer and all-cause mortality than never-smokers. The next question is whether the effects of previous or current smoking could be ameliorated by eight ideal cardiovascular health metrics (ICVHMs). We aim to explore whether ICVHMs may counteract the risk of all-cause mortality among former and current smokers. The results showed that only former smokers with ≥6 ICVHMs exhibited a comparable risk of all-cause mortality with never smokers. Furthermore, current smokers even having ≥6 ICVHMs still exhibited a higher risk of all-cause mortality compared with never smokers.

Diagnostic performance and clinical impacts of metagenomic sequencing after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Metagenomic Next-Generation Sequencing (mNGS) is a rapid, non-culture-based, high-throughput technique for pathogen diagnosis. Despite its numerous advantages, only a few studies have investigated its use in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective analysis of 404 mNGS tests performed on 264 patients after allo-HSCT. The tests were divided into three groups (Phase A, B, C) based on the time spent hospitalized post-transplantation, and we evaluated the analytical performance of mNGS in comparison with conventional microbiological tests (CMT), while also analyzing its clinical utility for clinical impacts. RESULTS: Metagenomic sequencing demonstrated a significantly higher rate of positive microbiological findings as compared to CMT (334/404 (82.7 %) vs. 159/404 (39.4 %), respectively, P < 0.001). The detection rates by both mNGS and CMT varied across the three-phase (mNGS: A-60/89 (67.4 %), B-147/158 (93.0 %), C-125/157 (79.6 %), respectively, P < 0.001; CMT: A-21/89 (23.6 %), B-79/158 (50.0 %), C-59/157 (37.6 %), respectively, P < 0.001). The infection sites and types of pathogens were also different across the three phases. Compared to non-GVHD cases, mNGS detected more Aspergillus spp. and Mucorales in GVHD patients (Aspergillus: 12/102 (11.8 %) vs. 8/158 (5.1 %), respectively, P = 0.048; Mucorales: 6/102 (5.9 %) vs. 2/158 (1.3 %), respectively, P = 0.035). Forty-five (181/404) percent of mNGS tests yielded a positive impact on the clinical diagnosis, while 24.3 % (98/404) of tests benefited the patients in antimicrobial treatment. CONCLUSION: mNGS is an indispensable diagnostic tool in identifying pathogens and optimizing antibiotic therapy for hematological patients receiving allo-HSCT.

Immune-mediated diseases and risk of incident cardiovascular diseases: a prospective cohort study.

OBJECTIVES: Disorders of immune system may impact cardiovascular health; however, comprehensive study is lacking. We aimed to analyse the association of total and 20 individual immune-mediated diseases (IMDs) with risk of incident cardiovascular disease (CVD). METHODS: In this prospective cohort study, 414 495 participants (55.6% women; mean age 55.9 years) from UK Biobank with baseline assessment at 2006-10 were included. Among them, 21 784 participants had prevalent IMDs. Information on IMDs at baseline and incidence of CVDs during follow-up were recorded. Cox proportional hazard models were used to estimate the association between IMDs and CVDs risk. RESULTS: During the median follow-up of 12.1 years, there were 6506 cases of CVDs in participants with IMDs (29.9%) and 77 699 cases in those without IMDs (19.8%). After multivariable adjustment, participants with IMDs were significantly associated with an increased risk of total CVD [hazard ratio (HR) 1.57; 95% CI 1.52-1.61]. Among the 20 IMDs, 16 showed significant associations with CVD (all P < 0.0025 after Bonferroni correction), with HR ranging from 1.34 (1.16-1.54) for celiac disease to 2.75 (2.10-3.61) for SLE. Participants with any IMD exposure had a higher risk of all individual CVD events, with HR ranging from 1.34 (1.14-1.58) for cerebral hemorrhage to 1.80 (1.54-2.11) for pericardium diseases. IMD duration <5, 5-10 and >10 years was associated with 55%, 59% and 56% increased risk of total CVD, respectively. CONCLUSION: Total and individual IMDs were associated with an increased risk of overall CVDs. It is important to consider primary prevention of CVD in patients with IMD and dysregulation of immune system in the cardiovascular health.

Pulmonary strongyloidiasis and hyperinfection in a Patient with idiopathic inflammatory myopathy：A case report.

Pulmonary strongyloidiasis is a rare infection in patients with autoimmune diseases, and immunosuppression can lead to the development of hyperinfection syndrome with a high mortality rate. We present a case of a 78-year-old male with previous idiopathic inflammatory myopathy (IIM) with interstitial lung disease. He developed hyperinfection syndrome and respiratory failure, and diagnostic metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) confirmed the presence of Strongyloides stercoralis. After treatment with ivermectin, the patient's symptoms improved. Therefore, adequate screening and prophylactic treatment are needed for people at risk of immunosuppression, which can reduce the occurrence of the devastating S. stercoralis hyperinfection syndrome. It also highlights mNGS as a highly accurate test for the detection of difficult to atypical pathogens.

Life's Essential 8 and risk of non-communicable chronic diseases: Outcome-wide analyses.

BACKGROUND: Life's Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life's Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life's Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs. METHODS: In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined. RESULTS: During the median follow-up of 10.85 years, 58,889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%). CONCLUSIONS: Improving CVH score based on Life's Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, normal weight may especially important to prevent new cases of metabolic diseases, NCDs in digestive system and mental and behavioral disorders, and cancer.

Nonalcoholic fatty liver disease and type 2 diabetes: an observational and Mendelian randomization study.

Introduction: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are both chronic multisystem diseases that cause tremendous health burdens worldwide. Previous epidemiological studies have found a bidirectional relationship between these two diseases; however, their causality remains largely unknown. We aim to examine the causal relationship between NAFLD and T2DM. Methods: The observational analysis included 2,099 participants from the SPECT-China study and 502,414 participants from the UK Biobank. Logistic regression and Cox regression models were used to examine the bidirectional association between NAFLD and T2DM. Two-sample Mendelian randomization (MR) analyses were conducted to investigate the causal effects of the two diseases using summary statistics of genome-wide association studies from the UK Biobank for T2DM and the FinnGen study for NAFLD. Results: During the follow-up, 129 T2DM cases and 263 NAFLD cases were observed in the SPECT-China study, and 30,274 T2DM cases and 4,896 NAFLD cases occurred in the UK Biobank cohort. Baseline NAFLD was associated with an increased risk of incident T2DM in both studies (SPECT-China: OR: 1.74 (95% confidence interval (CI): 1.12-2.70); UK Biobank: HR: 2.16 (95% CI: 1.82-2.56)), while baseline T2DM was associated with incident NAFLD in the UK Biobank study only (HR: 1.58). Bidirectional MR analysis showed that genetically determined NAFLD was significantly associated with an increased risk of T2DM (OR: 1.003 (95% CI: 1.002-1.004, p< 0.001)); however, there was no evidence of an association between genetically determined T2DM and NAFLD (OR: 28.1 (95% CI: 0.7-1,143.0)). Conclusions: Our study suggested the causal effect of NAFLD on T2DM development. The lack of a causal association between T2DM and NAFLD warrants further verification.

Investigating the shared genetic architecture between schizophrenia and body mass index.

Evidence for reciprocal comorbidity of schizophrenia (SCZ) and body mass index (BMI) has grown in recent years. However, little is known regarding the shared genetic architecture or causality underlying the phenotypic association between SCZ and BMI. Leveraging summary statistics from the hitherto largest genome-wide association study (GWAS) on each trait, we investigated the genetic overlap and causal associations of SCZ with BMI. Our study demonstrated a genetic correlation between SCZ and BMI, and the correlation was more evident in local genomic regions. The cross-trait meta-analysis identified 27 significant SNPs shared between SCZ and BMI, most of which had the same direction of influence on both diseases. Mendelian randomization analysis showed the causal association of SCZ with BMI, but not vice versa. Combining the gene expression information, we found that the genetic correlation between SCZ and BMI is enriched in six regions of brain, led by the brain frontal cortex. Additionally, 34 functional genes and 18 specific cell types were found to have an impact on both SCZ and BMI within these regions. Taken together, our comprehensive genome-wide cross-trait analysis suggests a shared genetic basis including pleiotropic loci, tissue enrichment, and shared function genes between SCZ and BMI. This work provides novel insights into the intrinsic genetic overlap of SCZ and BMI, and highlights new opportunities and avenues for future investigation.

Association between Life's Essential 8 score and risk of premature mortality in people with and without type 2 diabetes: A prospective cohort study.

AIMS: To evaluate the association of cardiovascular health (CVH), measured by Life's Essential 8 score, with the risk of premature mortality and to determine the patterns of CVH-related differences in life expectancy among people with and without type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 309,789 participants (age 56.6 ± 8.1 years; 46% men) enroled in the UK Biobank. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (BMI, non-HDL cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH was categorised into low, moderate, and high groups. Premature death was defined as death before the age of 75. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and life expectancy was estimated. RESULTS: During a median follow-up of 12.7 years, 13,683 cases of premature death were documented. Compared to participants with low CVH, the multivariable HRs (95% CIs) of premature death were 0.59 (0.56-0.62) and 0.42 (0.39-0.45) for the moderate and high CVH groups, respectively. This association was stronger in participants with T2D compared with those without T2D. At the age of 50 years, compared to low CVH groups, high CVH was associated with a gain of 9.79 (9.70-9.87) and 5.58 (5.48-5.67) additional life years for men with and without T2D, respectively. The corresponding life gain for women with and without T2D was 24.21 (24.13-24.27) and 10.18 (10.10-10.27), respectively. CONCLUSIONS: Maintaining an ideal Life's Essential 8 score may provide more benefits for people with T2D than for those without T2D, including a lower risk of premature death and an increased lifespan.

Association between Mean Arterial Pressure during the First 24 Hours and Clinical Outcome in Critically Ill Stroke Patients: An Analysis of the MIMIC-III Database.

Abnormal blood pressure is common in critically ill stroke patients. However, the association between mean arterial pressure (MAP) and mortality of critically ill stroke patients remains unclear. We extracted eligible acute stroke patients from the MIMIC-III database. The patients were divided into three groups: a low MAP group (MAP ≤ 70 mmHg), a normal MAP group (70 mmHg < MAP ≤ 90 mmHg), and a high MAP group (MAP > 90 mmHg). The Cox proportional hazards model and restricted cubic splines were used to assess the association between MAP and mortality. Sensitivity analyses were conducted to investigate whether MAP had different effects on mortality in different subpopulations. A total of 2885 stroke patients were included in this study. The crude 7-day and 28-day mortality was significantly higher in the low MAP group than that in the normal MAP group. By contrast, patients in the high MAP group did not have higher crude 7-day and 28-day mortality than those in the normal MAP group. After multiple adjustments using the Cox regression model, patients with low MAP were consistently associated with higher 7-day and 28-day mortality than those with normal MAP in the following subgroups: age > 60 years, male, those with or without hypertension, those without diabetes, and those without CHD (p < 0.05), but patients with high MAP were not necessarily associated with higher 7-day and 28-day mortality after adjustments (most p > 0.05). Using the restricted cubic splines, an approximately L-shaped relationship was established between MAP and the 7-day and 28-day mortality in acute stroke patients. The findings were robust to multiple sensitivity analyses in stroke patients. In critically ill stroke patients, a low MAP significantly increased the 7-day and 28-day mortality, while a high MAP did not, suggesting that a low MAP is more harmful than a high MAP in critically ill stroke patients.

Utility of plasma cell-free DNA next-generation sequencing for diagnosis of infectious diseases in patients with hematological disorders.

BACKGROUND: Plasma cell-free DNA Next-Generation Sequencing has been used as a non-invasive and comprehensive method for the etiological diagnosis of infectious diseases. However, only a handful of studies have described the real-world utility of this technique in patients with hematological disorders, a cohort of patients that are distinctive due to neutropenia and weakened immune functions. METHODS: We retrospectively analyzed the results of plasma cell-free DNA sequencing performed on 184 and 163 specimens collected from hematological patients suspected of infections with (Group I) or without (Group II) neutropenia, respectively. The diagnostic performance and the clinical impact of plasma sequencing were comparatively evaluated to conventional microbiological tests and a composite reference standard (conventional tests combined with the clinical assessment). RESULTS: The overall positive detection rate of plasma cell-free DNA sequencing was significantly higher than that of conventional microbiological tests (72.6% vs.31.4%, P < 0.001). The positive rate of conventional microbiological tests in Group I was lower than that in Group II (25.5% vs. 38.0%, P = 0.012). Combining plasma sequencing with conventional tests yielded a positive detection rate of 75.0% and 74.8% for these two groups, respectively. Using the composite reference standard, the sensitivity and specificity of plasma sequencing were 89.1% and 65.1%, respectively. The proportions of the positive impact of cell-free DNA sequencing results in the Group I were higher than in the Group II in terms of both diagnosis and treatment (diagnosis: 54.3% vs. 40.5%, P = 0.013; treatment: 45.7% vs.30.7%, P = 0.004). A total of 73 patients (21.0%) benefited from plasma sequencing through adjustment of the antibiotic regimen. CONCLUSIONS: The diagnostic yield of conventional microbiological tests was low in patients with neutropenia. Combining conventional tests with plasma cell-free DNA sequencing significantly improved the detection rate for pathogens and optimized antibiotic treatment. Our findings on the clinical impact warrant confirmation through larger, multicenter, randomized controlled trials. Moreover, the cost-effectiveness of this testing strategy remains unknown and requires further exploration.

A comparative bibliometric analysis of Omicron and Delta variants during the COVID-19 pandemic.

BACKGROUND: To compare the research hotspots of infections with the Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic and to identify future research trends. METHODS: Studies about Delta and Omicron variant infections published over the last 3 years were retrieved from the Web of Science (WoS) database. A comparative bibliometric analysis was conducted through machine learning and visualization tools, including VOSviewer, Bibliographic Item Co-Occurrence Matrix Builder, and Graphical Clustering Toolkit. Research hotspots and trends in the field were analyzed, and the contributions and collaborations of countries, institutions, and authors were documented. A cross-sectional analysis of the relevant studies registered at ClinicalTrials.gov was also performed to clarify the direction of future research. RESULTS: A total of 1,787 articles distributed in 107 countries and 374 publications from 77 countries focused on the Delta and Omicron variants were included in our bibliometric analysis. The top five productive countries in both variants were the USA, China, the UK, India, and Germany. In 5,999 and 1,107 keywords identified from articles on the Delta and Omicron, the top two frequent keywords were the same: "COVID-19" (occurrence: 713, total link strength: 1,525 in Delta; occurrence: 137, total link strength: 354 in Omicron), followed by "SARS-CoV-2" (occurrence: 553, total link strength: 1,478 in Delta; occurrences 132, total link strength: 395 in Omicron). Five theme clusters from articles on Delta variant were identified: transmission, molecular structure, activation mode, epidemiology, and co-infection. While other three theme clusters were recognized for the Omicron variant: vaccine, human immune response, and infection control. Meanwhile, 21 interventional studies had been registered up to April 2022, most of which aimed to evaluate the immunogenicity and safety of different kinds of vaccines in various populations. CONCLUSIONS: Publications and clinical trials related to COVID-19 increased annually. As the first comparative bibliometric analysis for Delta and Omicron variants, we noticed that the relevant research trends have shifted from vaccine development to infection control and management of complications. The ongoing clinical studies will verify the safety and efficacy of promising drugs.

Replacement of leisure-time sedentary behavior with various physical activities and the risk of dementia incidence and mortality: A prospective cohort study.

BACKGROUND: Whether or not there is targeted pharmacotherapy for dementia, an active and healthy lifestyle that includes physical activity (PA) may be a better option than medication for preventing dementia. We examined the association between leisure-time sedentary behavior (SB) and the risk of dementia incidence and mortality. We further quantified the effect on dementia risk of replacing sedentary time with an equal amount of time spent on different physical activities. METHODS: In the UK Biobank, 484,169 participants (mean age = 56.5 years; 45.2% men) free of dementia were followed from baseline (2006-2010) through July 30, 2021. A standard questionnaire measured individual leisure-time SB (watching TV, computer use, and driving) and PA (walking for pleasure, light and heavy do-it-yourself activity, strenuous sports, and other exercise) frequency and duration in the 4 weeks prior to evaluation. Apolipoprotein E (APOE) genotype data were available for a subset of 397,519 (82.1%) individuals. A Cox proportional hazard model and an isotemporal substitution model were used in this study. RESULTS: During a median 12.4 years of follow-up, 6904 all-cause dementia cases and 2115 deaths from dementia were recorded. In comparison to participants with leisure-time SB <5 h/day, the hazard ratio ((HR), 95% confidence interval (95%CI)) of dementia incidence was 1.07 (1.02-1.13) for 5-8 h/day and 1.25 (1.13-1.38) for >8 h/day, and the HR of dementia mortality was 1.35 (1.12-1.61) for >8 h/day. A 1 standard deviation increment of sedentary time (2.33 h/day) was strongly associated with a higher incidence of dementia and mortality (HR = 1.06, 95%CI: 1.03-1.08 and HR = 1.07, 95%CI: 1.03-1.12, respectively). The association between sedentary time and the risk of developing dementia was more profound in subjects <60 years than in those ≥60 years (HR = 1.26, 95%CI: 1.00-1.58 vs. HR = 1.21, 95%CI: 1.08-1.35 in >8 h/day, p for interaction = 0.013). Replacing 30 min/day of leisure sedentary time with an equal time spent in total PA was associated with a 6% decreased risk and 9% decreased mortality from dementia, with exercise (e.g., swimming, cycling, aerobics, bowling) showing the strongest benefit (HR = 0.82, 95%CI: 0.78-0.86 and HR = 0.79, 95%CI: 0.72-0.86). Compared with APOE ε4 noncarriers, APOE ε4 carriers are more likely to see a decrease in Alzheimer's disease incidence and mortality when PA is substituted for SB. CONCLUSION: Leisure-time SB was positively associated with the risk of dementia incidence and mortality. Replacing sedentary time with equal time spent doing PA may be associated with a significant reduction in dementia incidence and mortality risk.

Prophylactic effect of low-dose trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia in adult recipients of kidney transplantation: a real-world data study.

OBJECTIVES: To evaluate the efficacy and safety of low-dose trimethoprim (TMP)-sulfamethoxazole (SMX) (TMP-SMX) as the primary prophylaxis for Pneumocystis jirovecii pneumonia (PJP) in adult recipients of kidney transplantation. METHODS: Three kinds of prescriptions in kidney recipients were documented, including 20 mg TMP/100 mg SMX oral daily, 20 mg TMP/100 mg SMX oral every other day, and nonprophylaxis. The primary outcome was the incidence of PJP in the first 180 days of follow-up after kidney transplantation. The secondary outcomes were changes in renal and liver function. RESULTS: Among the 1469 recipients, 1066 (72.56%) received 20 mg TMP/100 mg SMX daily, 127 (8.65%) received 20 mg TMP/100 mg SMX every other day, and 276 (18.79%) did not have prophylaxis prescription. The 276 recipients in the nonprophylaxis group had 124.92 person-years of follow-up, during which PJP occurred in 29 patients, for an incidence rate of 23.21 (95% confidence interval 15.76-32.72) per 100 person-years. The TMP-SMX daily group and the TMP-SMX every other day group had 524.89 and 62.07 person-years of follow-up, respectively, with no occurrence of PJP. There was no significant difference among the three groups in changes in renal and liver function (P >0.05, respectively). A total of 111 recipients in each group were enrolled in the propensity score matching analysis. It was revealed that the 111 nonprophylaxis recipients had 51.27 person-years of follow-up and 10 PJP cases. Prophylaxis was considered effective because there was a significant difference between the three groups (P <0.001). CONCLUSION: Low-dose TMP-SMX prophylaxis significantly reduces the incidence of PJP within 6 months after kidney transplantation and has a favorable safety profile.

A bibliometric analysis of the application of artificial intelligence to advance individualized diagnosis and treatment of critical illness.

Background: Artificial intelligence (AI) has been extensively applied in the individualized diagnosis and treatment of critical illness, and numerous studies have been published on this topic. Therefore, a bibliometric analysis of these publications should be performed to provide a direction of hot topics and future research trends. Methods: A bibliometric analysis was performed on the research articles to identify the hot topics and any unsolved issues regarding the use of AI in individualized diagnosis and treatment of critical illness. Articles published from January 2011 to December 2021 were retrieved from the Web of Science (WOS) core collection database for bibliometric analysis, and a cross-sectional analysis of the relevant studies that had been registered at ClinicalTrials.gov was also conducted. Results: The number of articles published showed an annually increasing trend, with a worldwide geographic distribution over the past decade. Ultimately, 427 research articles were included in the bibliometric analysis. The relevant articles were divided into four separate clusters that focused on AI application aspects, prediction model establishment, coronavirus disease 2019 (COVID-19) treatment and outcome assessments, respectively. "Machine learning" was the most frequent keyword (147 occurrences, 165 links, and 395 total link strengths) followed by "risk", "models", and "mortality". With 205 articles, the United States of America (USA) had interacted the most with other countries (20 links, and 94 total link strength), while the domestic research institutes in China had infrequently collaborated with others. Approximately 130 trials focusing on the application of AI in the intensive care unit (ICU) and emergency department (ED) had been registered at ClinicalTrial.gov, and most of them (n=71, 54.6%) were interventional. The main research objectives of these trials were to provide decision making assistance and establish prediction models. However, only 3.8% (5 trials) of them had reached exact conclusions which favored the application of AI. Conclusions: The application of AI has raised great interest in critical illness and has mainly been focused on decision making assistance and prediction model establishment. Cooperation between agencies engaged in AI research needs to be strengthened. An increasing number of trials have been registered at ClinicalTrial.gov, and the results of them are promising. Keywords: Bibliometric analysis; artificial intelligence (AI); individualized diagnosis; critical care medicine; emergency department (ED).

A simple nomogram for predicting infectious diseases in adult kidney transplantation recipients.

Objective: To investigate the risk factors of infectious diseases in adult kidney transplantation recipients and to establish a simple and novel nomogram to guide the prophylactic antimicrobial therapy. Methods: Patients who received kidney transplantation between January 2018 and October 2021 were included in the study and were divided into a training and a testing set at a 1:1 ratio. Risk factors correlated to infectious diseases were selected using a Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The prediction model was built by incorporating the variables selected by the LASSO model into a logistic regression equation. Calibration curves and receiver operating characteristic (ROC) curves were also applied to assess the model calibration and discrimination. A nomogram consisting of the selected factors was established to provide individualized risks of developing infections. Decision curve analysis (DCA) was adopted to estimate the net benefit and reduction in interventions for a range of clinically reasonable risk thresholds. Results: In all, 863 adult kidney recipients were included in the study, and 407 (47.16%) of them developed infectious diseases during the 3-year follow-up period. A total of 8 variables were selected using LASSO regression and were retained for subsequent model construction and infection prediction. The area under the curve (AUC) was 0.83 and 0.81 in the training and testing sets, with high F scores of 0.76 and 0.77, sensitivity of 0.76 and 0.81, and specificity of 0.88 and 0.74, respectively. A novel nomogram was developed based on 8 selected predictors (requirement for albumin infusion, requirement for red blood cell infusion, triglyceride, uric acid, creatinine, globulin, neutrophil percentage, and white blood cells). The net benefit indicated that the nomogram would reduce unnecessary interventions at a wide range of threshold probabilities in both sets. Conclusions: Adult kidney transplantation recipients are high-risk hosts for infectious diseases. The novel nomogram consisting of 8 factors reveals good predictive performance and may promote the reasonable antimicrobial prescription. More external validations are required to confirm its effectiveness for further clinical application.