Identifying novel subgroups in heart failure patients with unsupervised machine learning: A scoping review.

Background: Heart failure is currently divided into three main forms, HFrEF, HFpEF, and HFmrEF, but its etiology is diverse and highly heterogeneous. Many studies reported a variety of novel subgroups in heart failure patients, with unsupervised machine learning methods. The aim of this scoping review is to provide insights into how these techniques can diagnose and manage HF faster and better, thus providing direction for future research and facilitating its routine use in clinical practice. Methods: The review was performed following PRISMA-SCR guideline. We searched the PubMed database for eligible publications. Studies were included if they defined new subgroups in HF patients using clustering analysis methods, and excluded if they are (1) Reviews, commentary, or editorials, (2) Studies not about defining new sub-types, or (3) Studies not using unsupervised algorithms. All study screening and data extraction were conducted independently by two investigators and narrative integration of data extracted from included studies was performed. Results: Of the 498 studies identified, 47 were included in the analysis. Most studies (61.7%) were published in 2020 and later. The largest number of studies (46.8%) coming from the United States, and most of the studies were authored and included in the same country. The most commonly used machine learning method was hierarchical cluster analysis (46.8%), the most commonly used cluster variable type was comorbidity (61.7%), and the least used cluster variable type was genomics (12.8%). Most of the studies used data sets of less than 500 patients (48.9%), and the sample size had negative correlation with the number of clustering variables. The majority of studies (85.1%) assessed the association between cluster grouping and at least one outcomes, with death and hospitalization being the most commonly used outcome measures. Conclusion: This scoping review provides an overview of recent studies proposing novel HF subgroups based on clustering analysis. Differences were found in study design, study population, clustering methods and variables, and outcomes of interests, and we provided insights into how these studies were conducted and identify the knowledge gaps to guide future research.

Elevated Fasting Blood Glucose Levels Are Associated with Worse Clinical Outcomes in COVID-19 Patients Than in Pneumonia Patients with Bacterial Infections.

Aims: We investigate how fasting blood glucose (FBG) levels affect the clinical severity in coronavirus disease 2019 (COVID-19) patients, pneumonia patients with sole bacterial infection, and pneumonia patients with concurrent bacterial and fungal infections. Methods: We enrolled 2761 COVID-19 patients, 1686 pneumonia patients with bacterial infections, and 2035 pneumonia patients with concurrent infections. We used multivariate logistic regression analysis to assess the associations between FBG levels and clinical severity. Results: FBG levels in COVID-19 patients were significantly higher than in other pneumonia patients during hospitalisation and at discharge (all p < 0.05). Among COVID-19 patients, the odds ratios of acute respiratory distress syndrome (ARDS), respiratory failure (RF), acute hepatitis/liver failure (AH/LF), length of stay, and intensive care unit (ICU) admission were 12.80 (95% CI, 4.80−37.96), 5.72 (2.95−11.06), 2.60 (1.20−5.32), 1.42 (1.26−1.59), and 5.16 (3.26−8.17) times higher in the FBG ≥7.0 mmol/L group than in FBG < 6.1 mmol/L group, respectively. The odds ratios of RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with sole bacterial infection (3.70 [2.21−6.29]; 1.56 [1.17−2.07]; 0.98 [0.88−1.11]; 2.06 [1.26−3.36], respectively). The odds ratios of ARDS, RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with concurrent infections (3.04 [0.36−6.41]; 2.31 [1.76−3.05]; 1.21 [0.97−1.52]; 1.02 [0.93−1.13]; 1.72 [1.19−2.50], respectively). Among COVID-19 patients, the incidence rate of ICU admission on day 21 in the FBG ≥ 7.0 mmol/L group was six times higher than in the FBG < 6.1 mmol/L group (12.30% vs. 2.21%, p < 0.001). Among other pneumonia patients, the incidence rate of ICU admission on day 21 was only two times higher. Conclusions: Elevated FBG levels at admission predict subsequent clinical severity in all pneumonia patients regardless of the underlying pathogens, but COVID-19 patients are more sensitive to FBG levels, and suffer more severe clinical complications than other pneumonia patients.

Characteristics and Prognosis of Antibody Non-responders With Coronavirus Disease 2019.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been spreading globally. Information regarding the characteristics and prognosis of antibody non-responders to COVID-19 is limited. Methods: In this retrospective, single-center study, we included all patients with confirmed COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) admitted to the Fire God Mountain hospital from February 3, 2020, to April 14, 2020. A total of 1,921 patients were divided into the antibody-negative (n = 94) and antibody-positive (n = 1,827) groups, and 1:1 propensity score matching was used to match the two groups. Results: In the antibody-negative group, 40 patients (42.6%) were men, and 49 (52.1%) were older than 65 years. Cough was the most common symptom in the antibody negative group. White blood cell counts, neutrophils, C-reactive protein, procalcitonin, interleukin-6, lactate dehydrogenase, creatine kinase, creatine kinase isoenzyme, urea nitrogen, and creatinine were significantly higher in the antibody-negative patients than in the antibody-positive group (P < 0.005). The number of days of nucleic acid-negative conversion in the antibody-negative group was shorter than that in the antibody-positive group (P < 0.001). The hospitalization time of the antibody-negative patients was shorter than that of the antibody-positive patients (P < 0.001). Conclusion: Some COVID-19 patients without specific antibodies had mild symptoms; however, the inflammatory reaction caused by innate clinical immunity was more intense than those associated with antibodies. Non-specific immune responses played an essential role in virus clearance. There was no direct correlation between excessive inflammatory response and adverse outcomes in patients. The risk of reinfection and vaccination strategies for antibody-negative patients need to be further explored.

High Fasting Blood Glucose Level With Unknown Prior History of Diabetes Is Associated With High Risk of Severe Adverse COVID-19 Outcome.

Background: We aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications. Methods: We enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG<6.1mmol/L with no history of diabetes (group 1), patients with FBG<6.1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients. Results: COVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70%; critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p<0.05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P<0.001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P<0.001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3. Conclusion: Our study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels.

Elevated glucose level leads to rapid COVID-19 progression and high fatality.

OBJECTIVES: We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients. METHODS: We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality. RESULTS: The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8-5.5), 3.0 (1.0-7.0), 3.0 (1.0-8.0), and 6.5 (4.0-16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19. CONCLUSIONS: Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.

Assisting scalable diagnosis automatically via CT images in the combat against COVID-19.

The pandemic of Coronavirus Disease 2019 (COVID-19) is causing enormous loss of life globally. Prompt case identification is critical. The reference method is the real-time reverse transcription PCR (RT-PCR) assay, whose limitations may curb its prompt large-scale application. COVID-19 manifests with chest computed tomography (CT) abnormalities, some even before the onset of symptoms. We tested the hypothesis that the application of deep learning (DL) to 3D CT images could help identify COVID-19 infections. Using data from 920 COVID-19 and 1,073 non-COVID-19 pneumonia patients, we developed a modified DenseNet-264 model, COVIDNet, to classify CT images to either class. When tested on an independent set of 233 COVID-19 and 289 non-COVID-19 pneumonia patients, COVIDNet achieved an accuracy rate of 94.3% and an area under the curve of 0.98. As of March 23, 2020, the COVIDNet system had been used 11,966 times with a sensitivity of 91.12% and a specificity of 88.50% in six hospitals with PCR confirmation. Application of DL to CT images may improve both efficiency and capacity of case detection and long-term surveillance.

Independent and combined effects of hypertension and diabetes on clinical outcomes in patients with COVID-19: A retrospective cohort study of Huoshen Mountain Hospital and Guanggu Fangcang Shelter Hospital.

It is widely recognized that hypertension is one of the major risk factor for disease severity and mortality in patients with coronavirus disease 2019 (COVID-19). However, type 2 diabetes mellitus (T2DM) and hypertension are frequent comorbid conditions, complicating the assessment of hypertension's individual contribution to the risk. The aims of this study were to evaluate the contributions of hypertension alone, T2DM alone, or their combination to the risk of death, acute respiratory distress syndrome (ARDS)/respiratory failure, and severe COVID-19 infection. Additionally, we assessed risks associated with elevated blood pressure and fasting blood glucose on the same three clinical outcomes. Multivariate logistic models were used for these analyses. Among the 3400 patients, 3327(97.9%) survived and 73(2.1%) died. Compared to patients having neither hypertension nor T2DM (n = 1392), the risk of mortality was significantly higher in patients with T2DM alone (n = 226, OR 5.26 [95% CI: 2.39-11.58]) or with T2DM in combination with hypertension (n = 507, OR 3.02, [95% CI: 1.48-6.15]). Similarly, T2DM was a risk factor for development of ARDS/respiratory failure and severe infection. Hypertension alone (n = 1275) only conferred additional risk for the development of severe infection (OR 1.22 [95% CI: 1.00-1.51]). In conclusion, neither hypertension nor elevated blood pressure was independent risk factors for death or ARDS/respiratory failure but hypertension marginally increased the risk of severe COVID-19 infection. The risk associated with hypertension is accentuated through its confounding effect on T2DM.

Systemic Lupus Erythematosus and Angioedema: A Cross-Sectional Study From the National Inpatient Sample.

Objectives: This cross-sectional study aims to investigate the odds of developing angioedema (AE) in systemic lupus erythematosus (SLE) populations compared to non-SLE populations in hospital settings in the United States using a nationwide database. Materials and methods: We used the data from the National Inpatient Sample for the years 2012 to 2014. We constructed two models for multivariate logistic regression analysis. Model 1 was designed to adjust demographic information, while model 2 included each factor in model 1 and additionally accounted for AE-related comorbidities. Results: A total of 90,485 hospitalizations with an AE diagnosis were identified for the years 2012 to 2014, among which 1,505 hospitalizations had both SLE and AE. Compared to those without SLE, AE patients with SLE were younger and included more females. In AE hospitalizations, SLE was associated with higher odds of AE-related comorbidities including atopic disorder, leukocytoclastic vasculitis, eosinophilia, and infections. SLE was associated with higher odds of AE both as all inpatient diagnosis and as principal diagnosis (unadjusted odds ratio [OR] 3.24, 95% confidence interval [CI] 2.87-3.63, p<0.001, model 1 adjusted OR 2.54, 95% CI 2.26-2.86, p<0.001, model 2 adjusted OR 1.71, 95% CI 1.51-1.93, p<0.001). Conclusion: Our study demonstrates that SLE is associated with higher odds of having AE, including severe AE as the principal reason for inpatient admission. SLE is possibly an independent risk factor for AE.

Cystic and solitary nodular pulmonary metastases in a patient with low-grade endometrial stromal sarcoma: A case report and literature review.

Pulmonary metastases of endometrial stromal sarcoma (ESS) are uncommon and can be difficult to diagnose. The aims of the present study were to investigate the clinical and pathological features, and enhance the awareness of pulmonary metastases in patients with low-grade ESS. The study reports a case of low-grade ESS that resulted in cystic and nodular pulmonary metastases. Furthermore, the PubMed database was searched using 'pulmonary metastases of low-grade endometrial stromal sarcoma' as the key phrase. The literature on pulmonary metastases of low-grade ESS was reviewed and 35 cases were included in the present study. The clinical manifestations, imaging data, pathological features, treatment and prognosis of the 35 previously reported cases and the current case were retrospectively analyzed. The age range of the 36 patients diagnosed with low-grade ESS was 28-65 years. The time period from confirmation of ESS to lung metastases was 1.5-27 years. In 50% of the patients, the pulmonary metastases were asymptomatic. The most common pulmonary symptom was dyspnea, followed by chest pain, pneumothorax and coughing. The most common chest imaging presentation was multiple pulmonary nodules, followed by a solitary nodule or mass. Histology was used to identify that the pulmonary metastases had the pathological features of low-grade ESS. The immunohistochemical results demonstrated strong diffuse immunoreactivity for cluster of differentiation 10, estrogen receptor and progesterone receptor in almost all the specimens. The review of the literature revealed that pulmonary metastases from low-grade ESS are rare but not negligible. Furthermore, the detailed clinical information, imaging findings and immunohistochemical detection are important for making a diagnosis.

Validation of the RisingSun RS-651 Blood Pressure Monitor Based on Auscultation in Adults According to the ANSI/AAMI/ISO 81060-2:2013 Standard.

This study validated the RisingSun RS-651 blood pressure (BP) monitor based on auscultation in adults according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2013 standard. The RS-651 device was evaluated in a study of 97 participants. The same arm simultaneous method, as defined in the ANSI/AAMI/ISO standard, was used. The mean differences±standard deviation for criterion 1 were 0.8±2.3 mm Hg for systolic BP (SBP) and -0.1±2.9 mm Hg for diastolic BP (DBP). Analysis for criterion 2 resulted in values of 0.8±1.5 mm Hg for SBP and -0.1±2.1 mm Hg for DBP. All of the data fulfilled the ANSI/AAMI/ISO 81060-2:2013 standard requirements to pass the validation. The RisingSun RS-651 device can be recommended for both clinical and self/home use in adults according to the ANSI/AAMI/ISO 81060-2:2013 standard.

Brief communication: detection of clinical Klebsiella pneumoniae isolates from China containing transferable quinolone resistance determinants exhibiting resistance to both aminoglycoside and ß-lactams.

Though aminoglycosides are routinely used clinically as antimicrobial agents for the treatment of severe infections due to Klebsiella pneumoniae, resistance to the same is an increasing problem. One such resistance mechanism is the production of 16S rRNA methylases. The objective of the current study was to investigate the prevalence and molecular epidemology of 16S rRNA methylase genes among 43 K. pneumoniae isolates (each of which had at least one PQMR gene and ciprofloxacin minimum inhibitory concentration greater than 0.25) recovered from nine tertiary hospitals in China. Our results suggest great genetic variation in terms of 16S rRNA methylase gene of K. pneumoniae hosts containing at least one PQMR gene. This further reinforces the clinical and systemic urgency required to characterize and block their transmission routes.

Plasmid-mediated quinolone resistance--current knowledge and future perspectives.

Quinolones are a group of antimicrobial agents that were serendipitously discovered as byproducts of the synthesis of chloroquine. Chemical modifications, such as the addition of fluorine or piperazine, resulted in the synthesis of third- and fourth-generation fluoroquinolones, with broad-spectrum antimicrobial actions against aerobic or anaerobic, Gram-positive or Gram-negative bacteria. The efficacy and consequent widespread use of quinolones and fluoroquinolones has led to a steady global increase in resistance, mediated via gene mutations, alterations in efflux or cell membranes and plasmid-conferred resistance. The first plasmid-mediated quinolone resistance gene, qnrA1, was detected in 1998. Since then, many other genes have been identified and the underlying mechanisms of resistance have been elucidated. This review provides an overview of quinolone resistance, with particular emphasis on plasmid-mediated resistance.

[Antimicrobial resistance and genotyping of Acinetobacter baumannii in ICU].

OBJECTIVE: To investigate the outbreak of acinetobacter baumannii in the ICU, and to explore the antimicrobial resistance characteristics of pathogens, and therefore to determine the optimal prevention strategies. METHODS: From May to June 2007, most of the cases of infection by acinetobacter baumannii in our ICU were collected. PFGE (pulsed field gel electrophoresis) and standard disk diffusion susceptibility tests were performed on the strains isolated from the patients' body fluids including sputum, blood, urine, secretion and from the ICU environment involving the patients' bed sheet, skin surface and medical staff's hands, humidification water of ventilator tubes. RESULTS: Twelve strains were resistant to imipenem and meropenem. Colistin sulphate and tigecycline showed a high rate of antimicrobial activity against the strains, the rate of susceptibility being 100% and 91.7% respectively. These strains belonged to 3 clones (clone A, B, C) and there were 2 sub-clones (A1, A2) belonging to clone A. The sub-clone A1 was isolated from the surface of unwashed medical staff's hands and patients' body fluids. From intermediate to resistance, the antimicrobial characteristics of clone A and clone B to minocycline changed over a month, and there was one strain that was resistant to tigecycline. CONCLUSION: The outbreak of acinetobacter baumannii in the ICU was caused by carbapenem resistant acinetobacter baumannii (CRAb). The delicate changes of disk diffusion susceptibility in clones A and B occurred in one month. Unwashed hands of medical staff were probably responsible for the outbreak.

[Expression of high-level cephalosporinase due to mutation in the AmpC attenuator of a clinical Escherichia coli strain].

OBJECTIVE: To study the resistant phenotype of a clinical strain of Escherichia coli and to explore the effect of its attenuator mutation on AmpC expression. METHODS: A clinical strain of Escherichia coli 20022 (ECO20022) resistant to cefoxitin was isolated clinically. The phenotype was examined by three-dimensional methods, isoelectric focusing (IEF), and microdilution method. The regulator genes of ECO20022 were amplified and sequenced, and the difference between them was analyzed by BLAST method. Then the regulator genes were cloned into pCAT3-basic vector (a promoterless reporter gene vector). Microdilution method was used to detect the minimal inhibitory concentration (MIC) of chloramphenicol and ampicillin to this strain with E. coli ATCC25922 as quality control bacterium. ELISA was used to detect the content of chloramphenicol acetyl transferase (CAT). RESULTS: Compared to the standard E. coli K-12, there were four base substitutions, i.e., 22C-T, 26, 27TA-GT, and 32G-A in the attenuator region of ECO20022. Three-dimensional method showed that this strain was high AmpC-producing. IEF found that it produced three beta-lactamases with the values of PI of 5.4, 8.2, and 9.0 respectively. The beta-lactamase with the PI of 9.0 could be inhibited by cloxacillin but not by clavulanate. The strain was resistant to not only most of third generation cephalosporins, but also to cefepime; however it was still susceptible to carbapenem. The secondary structure of the attenuator RNA of ECO20022 was different from the traditional structure of E. coli K-12. The regulator gene was successfully cloned into pCAT3-basic vector and direct and indirect tests indicated that this regulator gene enhanced the CAT expressing level as much as 10 times that of Escherichia coli K-12. CONCLUSION: AmpC attenuator mutation leads to high AmpC expression in Escherichia coli, resulting in a significant rise of resistance level to beta-lactamase and a great menace to clinical antibiotic therapy.

[DHA-1 type cephalosporinase accompanied with SHV-12 prevailed in clinical isolates of Klebsiella pneumoniae].

OBJECTIVE: To study the prevalence, phenotype and genotype of the AmpC and ESBLs-producing clinical isolate of Klebsiella pneumoniae. METHODS: The clinical isolates of Klebsiella pneumoniae were examined by standard disk diffusion susceptibility tests, three-dimensional methods, isoelectric focusing (IEF) and microdilution methods. The conjugation experiment, multiplex PCR and DNA sequencing methods were used for further analysis. RESULTS: Four out of a total of 86 isolates tested were shown to be highly AmpC-producing by three-dimensional method. IEF showed that these strains produced a AmpC like beta-lactamase with a PI of 7.8, and DNA sequencing showed that the gene which expressed this AmpC like beta-lactamase was identical to DHA-1, a plasmid mediated cephalosporinase gene. These strains also produced an ESBL like beta-lactamase with a PI of 8.2 and the gene which expressed this beta-lactamase was identical to SHV-12. These strains were resistant not only to most of the third generation cephalosporins, but also to cefepime. However they were still susceptible to carbapenem. CONCLUSIONS: Highly AmpC-producing DHA-1 accompanied with SHV-12 in Klebsiella pneumoniae was reported here for the first time. They result in a significant rise in antibiotic resistance, which is regarded as a great challenge for clinical antibiotic therapy.

[A new member of CMY type cephalosporinase prevailing in Escherichia coli].

OBJECTIVE: To study the resistant phenotype and molecular biology character of plasmid mediated high AmpC-producing clinical isolates of Escherichia coli and to find new AmpC genotype. METHODS: The cefoxitin highly resistant clinical isolates of Escherichia coli were studied by K-B method, three-dimensional method, Isoelectric Focusing (IEF) and the MIC of these strains were examined by micro-dilution method. The conjugation experiment, multiplex PCR and DNA sequencing methods were used in further study. RESULTS: Above 719 strains studied, there are 6 isolates were showed as high AmpC-producing by three-dimensional method and IEF found they could produce a beta-Lactamase which PI was 8.9 and could be inhibited by cloxacillin but not by clavulnate. The strains were resistant to most of third generation cephalosporins, but were susceptible to cefepime, meropenem and imipenem. The experiment also showed that the gene which express this AmpC like beta-Lactamase could be transferable. Multiplex PCR indicated they belong to Citrobacter freundii family. Sequencing of corresponding DNA revealed 99% identities of the deduced amino acid sequence with CMY-2 and CMY-7 respectively. It is a new CMY type cephalosporinase. CONCLUSION: A new CMY type cephalosporinase has been found in clinical strains of Escherichia coli in our hospital. It was resistant to many antibiotics and its resistance could be transferred horizontally.