The Impact of FEV1/FVC Ratio on the Clinical Outcomes in Acute Coronary Syndrome Patients Treated with Dual Anti-Platelet Agents.

Background: Few studies have investigated the clinical efficacy and pulmonary side effects of different P2Y12 inhibitors in acute coronary syndrome (ACS) patients. The aim of this study was to explore the impact of forced expiratory volume in 1 second over forced vital capacity (FEV1/FVC) ratio on the clinical outcomes in ACS patients treated with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Methods: ACS patients who underwent PCI, had documented pre-existing spirometry tests, and received aspirin with either ticagrelor or clopidogrel were enrolled for retrospective analysis. Results: Of the enrolled ACS patients, 275 and 247 received ticagrelor and clopidogrel, respectively. The incidence of wheeze was significantly higher in the ticagrelor group compared to the clopidogrel group within 360 days (14.91% vs. 8.09%, p = 0.016). Multivariable analysis revealed that ticagrelor treatment, as compared to clopidogrel treatment, independently predicted 1-year hospitalization for acute exacerbation (AE) of obstructive airway disease (hazard ratio: 3.44; 95% confidence interval: 1.92 to 6.15; p < 0.01). The receiver operating characteristic curve indicated that an FEV1/FVC ratio of 63.85% had the highest sensitivity and specificity for predicting the incidence of AE of obstructive airway disease within 1 year (p < 0.001). The 1-year hospitalization rate for AE of obstructive airway disease was significantly higher in the ticagrelor group when the FEV1/FVC ratio was < 63%. Conclusions: This study demonstrated higher incidence of wheeze and hospitalization for AE of obstructive airway disease in ACS patients treated with ticagrelor compared to clopidogrel. Furthermore, the FEV1/FVC ratio ≤ 63% in the ACS patients predicted hospitalization for AE of obstructive airway disease in 1 year.

Delta Increment in Pacing QRS Duration Predicts Cardiovascular Mortality in Patients with Pre-Existing Bundle Branch Block Receiving Permanent Pacemakers.

Background: The clinical implication of pre-existing intraventricular conduction disturbance (IVCD) in permanent pacemaker (PPM) recipients is unknown. Objectives: To explore the clinical outcomes in patients with pre-existing IVCD after implantation of PPMs. Methods: A total of 1424 patients who received PPMs were categorized into three groups by pre-procedural electrocardiography: patients without IVCD (n = 1045), patients with right bundle branch block (RBBB) (n = 309), and patients with left bundle branch block (LBBB) (n = 70). The primary outcome was cardiovascular (CV) mortality. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off values of variable in predicting CV mortality. Results: During follow-up, there was no significant difference in CV mortality between patients with and without IVCD. In multivariate analysis, independent predictors of CV mortality were age [hazard ratio (HR): 1.03; 95% confidence interval (95% CI): 1.00-1.05; p = 0.026], history of heart failure [HR: 1.98; 95% CI: 1.19-3.29; p = 0.009], chronic kidney disease [HR: 1.75; 95% CI: 1.11-2.74; p = 0.015] and increment in pacing QRS duration [HR: 1.01; 95% CI: 1.00-1.04; p = 0.038]. Delta increments in pacing QRS duration ≥ 43 msec [HR: 2.91; 95% CI: 1.23-6.83; p = 0.014] in patients with pre-existing RBBB, and ≥ 33 msec [HR: 11.44; 95% CI: 2.03-64.30; p = 0.006] in patients with pre-existing LBBB were independent determinants of CV mortality. Conclusions: There was no difference in CV mortality between patients with or without IVCD. However, wider pacing QRS duration increased the risk of CV mortality in PPM recipients, and delta increment in pacing QRS duration increased the risk of CV mortality in patients with pre-existing IVCD.

The Performance of Risk Scores for Bleeding and Ischemia as Outcome Predictors in Acute Myocardial Infarction Patients with End-Stage Renal Disease.

Background: In patients with end-stage renal disease (ESRD), acute myocardial infarction (AMI) increases the risks of cardiovascular events, death, and bleeding. Several scores have been developed for predicting ischemic and bleeding outcomes in AMI patients, but none have been validated specifically for ESRD patients. Objectives: To compare and validate different risk scores as predictors of ischemic and bleeding outcomes in AMI patients with ESRD. Methods: This retrospective study enrolled 340 patients who had received percutaneous coronary intervention for AMI while undergoing maintenance hemodialysis for ESRD. Ischemic risk scores (TIMI-STEMI, TIMI-NSTEMI, GRACE, DAPT) and bleeding risk scores (PRECISE-DAPT, CRUSADE, ACUITY, ACTION, SWEDEHEART) were calculated. The ischemic outcome mainly focused on major adverse cardiovascular events (MACEs) within 14 days after hospitalization, and the bleeding outcome was 14-day major bleeding according to the CRUSADE criteria. Results: The GRACE score was superior in discriminating ischemic outcomes, especially in 14-day MACEs [area under curve (AUC) 0.791, p < 0.001]. None of the scores could ideally discriminate 14-day CRUSADE major bleeding, while the PRECISE- DAPT score had the best discriminative power (AUC 0.636, p < 0.001). Either GRACE score > 222 or PRECISE-DAPT score > 48 was associated with higher net adverse cardiovascular events (a composite of 14-day MACEs and 14-day CRUSADE major bleeding). Conclusions: In AMI patients with ESRD, the GRACE score can effectively discriminate the risk of short-term ischemic events. None of the scores could ideally discriminate the bleeding risk, but a high PRECISE-DAPT score still represented a higher rate of bleeding events.

Clinical Characteristics of Actinomyces viscosus Bacteremia.

Background and Objectives: Actinomyces species are part of the normal flora of humans and rarely cause disease. It is an uncommon cause of disease in humans. The clinical features of actinomycosis have been described, and various anatomical sites (such as face, bones and joints, respiratory tract, genitourinary tract, digestive tract, central nervous system, skin, and soft tissue structures) can be affected. It is not easy to identify actinomycosis because it sometimes mimics cancer due to under-recognition. As new diagnostic methods have been applied, Actinomyces can now more easily be identified at the species level. Recent studies have also highlighted differences among Actinomyces species. We report a case of Actinomyces viscosus bacteremia with cutaneous actinomycosis. Materials and Methods: A 66 years old male developed fever for a day with progressive right lower-leg erythematous swelling. Blood culture isolates yielded Actinomyces species, which was identified as Actinomyces viscosus by sequencing of the 16S rRNA gene. In addition, we searched for the term Actinomyces or actinomycosis cross-referenced with bacteremia or "blood culture" or "blood stream" from January 2010 to July 2020. The infectious diseases caused by species of A. viscosus from January 1977 to July 2020 were also reviewed. Results: The patient recovered well after intravenous ampicillin treatment. Poor oral hygiene was confirmed by dental examination. There were no disease relapses during the following period. Most cases of actinomycosis can be treated with penicillin. However, clinical alertness, risk factor evaluation, and identification of Actinomyces species can prevent inappropriate antibiotic or intervention. We also compiled a total of 18 cases of Actinomyces bacteremia after conducting an online database search. Conclusions: In summary, we describe a case of fever and progressive cellulitis. Actinomyces species was isolated from blood culture, which was further identified as Actinomyces viscosus by 16S rRNA sequencing. The cellulitis improved after pathogen-directed antibiotics. Evaluation of risk factors in patients with Actinomyces bacteremia and further identification of the Actinomyces species are recommended for successful treatment.

Fuzzy Adaptive Cubature Kalman Filter for Integrated Navigation Systems.

This paper presents a sensor fusion method based on the combination of cubature Kalman filter (CKF) and fuzzy logic adaptive system (FLAS) for the integrated navigation systems, such as the GPS/INS (Global Positioning System/inertial navigation system) integration. The third-degree spherical-radial cubature rule applied in the CKF has been employed to avoid the numerically instability in the system model. In processing navigation integration, the performance of nonlinear filter based estimation of the position and velocity states may severely degrade caused by modeling errors due to dynamics uncertainties of the vehicle. In order to resolve the shortcoming for selecting the process noise covariance through personal experience or numerical simulation, a scheme called the fuzzy adaptive cubature Kalman filter (FACKF) is presented by introducing the FLAS to adjust the weighting factor of the process noise covariance matrix. The FLAS is incorporated into the CKF framework as a mechanism for timely implementing the tuning of process noise covariance matrix based on the information of degree of divergence (DOD) parameter. The proposed FACKF algorithm shows promising accuracy improvement as compared to the extended Kalman filter (EKF), unscented Kalman filter (UKF), and CKF approaches.

Uncertainty Comparison of Visual Sensing in Adverse Weather Conditions.

This paper focuses on flood-region detection using monitoring images. However, adverse weather affects the outcome of image segmentation methods. In this paper, we present an experimental comparison of an outdoor visual sensing system using region-growing methods with two different growing rules-namely, GrowCut and RegGro. For each growing rule, several tests on adverse weather and lens-stained scenes were performed, taking into account and analyzing different weather conditions with the outdoor visual sensing system. The influence of several weather conditions was analyzed, highlighting their effect on the outdoor visual sensing system with different growing rules. Furthermore, experimental errors and uncertainties obtained with the growing rules were compared. The segmentation accuracy of flood regions yielded by the GrowCut, RegGro, and hybrid methods was 75%, 85%, and 87.7%, respectively.

Characterization of CRISPR-Cas Systems in Shewanella algae and Shewanella haliotis: Insights into the Adaptation and Survival of Marine Pathogens.

CRISPR-Cas systems are adaptive immune mechanisms present in most prokaryotes that play an important role in the adaptation of bacteria and archaea to new environments. Shewanella algae is a marine zoonotic pathogen with worldwide distribution, which accounts for the majority of clinical cases of Shewanella infections. However, the characterization of Shewanella algae CRISPR-Cas systems has not been well investigated yet. Through whole genome sequence analysis, we characterized the CRISPR-Cas systems in S. algae. Our results indicate that CRISPR-Cas systems are prevalent in S. algae, with the majority of strains containing the Type I-F system. This study provides new insights into the diversity and function of CRISPR-Cas systems in S. algae and highlights their potential role in the adaptation and survival of these marine pathogens.

Pathogenic Detection by Metagenomic Next-generation Sequencing in Skin and Soft Tissue Infection.

BACKGROUND/AIM: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited. PATIENTS AND METHODS: From January 2020 to October 2021, 19 SSTI samples from 16 patients were collected in a single center (Taichung Veterans General Hospital, Taichung, Taiwan). The clinical samples were simultaneously subjected to mNGS and conventional bacterial culture methods to detect pathogens. Clinical characteristics were prospectively collected through electronic chart review. The microbiological findings from conventional bacterial culture and mNGS were analyzed and compared. RESULTS: The mNGS method detected a higher proportion of multiple pathogens in SSTIs compared to conventional bacterial culture methods. Pseudomonas spp. was among the most commonly identified Gram-negative bacilli using mNGS. Additionally, the mNGS method identified several rare pathogens in patients with SSTIs, including Granulicatella adiacens, Bacillus thuringiensis, and Bacteroides fragilis. Antimicrobial resistance genes were detected in 10 samples (52.6%) using the mNGS method, including genes for extended-spectrum beta-lactamase, Ambler class C ß-lactamases, and carbapenemase. CONCLUSION: mNGS not only plays an important role in the detection of pathogens in soft tissue infections, but also informs clinical professionals about the presence of additional microbes that may be important for treatment decisions. Further studies comparing conventional pathogen culture with the mNGS method in SSTIs are required.

Extended-Spectrum ß-Lactamases (ESBL) Producing Bacteria in Animals.

Animals have been identified as potential reservoirs and vectors of resistance genes, with studies showing that Gram-negative bacteria can acquire resistance through the horizontal transmission of resistance genes on plasmids. It is important to understand the distribution of antimicrobial-resistant bacteria and their drug-resistant genes in animals. Previous review articles mostly focused on a single bacterium or a single animal. Our objective is to compile all ESBL-producing bacteria isolated from various animals in recent years and provide a comprehensive viewpoint. Using a thorough PubMed literature search spanning from 1 January 2020 to 30 June 2022, studies exploring extended-spectrum beta-lactamase (ESBL) producing bacteria in animals were included. ESBL-producing bacteria are present in animals from various countries around the world. The most common sources of these bacteria were farm animals, and the most frequently isolated bacteria were Escherichia coli and Klebsiella pneumoniae. The most detected ESBL genes were blaTEM, blaSHV, and blaCTX-M. The presence of ESBL-producing bacteria in animals highlights the importance of the One Health approach to address the issue of antibiotic resistance. Further research is needed to better understand the epidemiology and mechanisms of the spread of ESBL-producing bacteria in animal populations and their potential impact on human and animal health.

Comparative Genomics Identified PenR E151V Substitution Associated with Carbapenem-Resistance Burkholderia cepacia Complex and a Novel Burkholderia cepacia Complex Specific OXA-1043 Subgroup.

Purpose: Burkholderia cepacia complex (Bcc) is a known significant opportunistic pathogen causing morbidity and mortality, particularly in those with cystic fibrosis, chronic granulomatous disease, or immunocompromising host. Mortality of Bcc bloodstream infections among non-cystic fibrosis patients remained high. The antibiotic treatment for Bcc infection is quite challenging due to its intrinsic resistance to most antibiotics, and the resistance to carbapenems was the biggest concern among them. We aimed to realize the mechanism of carbapenem resistance in Bcc. Patients and Methods: Ten strains of Bcc were identified by the MALDI-TOF MS, and the drug susceptibility test was using VITEK 2 system. The Burkholderia cepacia complex genomes were sequenced via Nanopore GridIon. We also downloaded another ninety-five strains of Bcc from the National Center for Biotechnology Information database to evaluate the divergence between carbapenem-resistance and carbapenem-sensitive strains. Results: The genetic organization between carbapenem-sensitive and carbapenem-resistant strains of Bcc showed no difference. However, in the carbapenem-sensitive strain, E151V substitution in PenR was detected. In addition, a novel specific OXA family subgroup, blaOXA-1043 in Burkholderia cenocepacia was discovered. Conclusion: The E151V substitution in PenR may be associated with carbapenem-sensitive in Bcc. Moreover, the V151E mutation in PenR may be related to the activation of PenB, leading to Bcc resistance to carbapenems. Besides, a novel OXA family subgroup, blaOXA-1043, was found in Burkholderia cenocepacia, which differs from the previous OXA family.

Identification of combinatorial mutations associated with colistin resistance in Shewanella algae.

Colistin is a last-resort antibiotic used to treat infections caused by drug-resistant gram-negative bacteria. However, the genetic mechanisms underlying colistin resistance in Shewanella algae are not well understood. In this study, we sequenced and compared the genomes of 23 mcr-negative colistin-resistant and sensitive S. algae samples from various sources. We applied a computational approach to identify combinatorial mutations associated with colistin resistance. Our analysis revealed a combination of three mutations (PmrB 451, PmrE168, PmrH292) that were strongly associated with colistin resistance in S. algae. This study provides insights into the genetic mechanisms of colistin resistance in S. algae and demonstrates the utility of a computational approach for identifying epistatic interactions among mutations. Identifying the genetic mutations responsible for colistin resistance in S. algae can inform the development of new treatments or strategies to combat infections caused by this emerging pathogen.

Insight into the Mechanisms of Carbapenem Resistance in Klebsiella pneumoniae: A Study on IS26 Integrons, Beta-Lactamases, Porin Modifications, and Plasmidome Analysis.

The emergence of carbapenem-resistant Klebsiella pneumoniae poses a significant threat to public health. In this study, we aimed to investigate the distribution and genetic diversity of plasmids carrying beta-lactamase resistance determinants in a collection of carbapenem-resistant K. pneumoniae blood isolates. Blood isolates of carbapenem-resistant K. pneumoniae bacteremia were collected and identified. Whole-genome sequencing, assembly and analysis were performed for the prediction of antimicrobial resistance determinants. Plasmidome analysis was also performed. Our plasmidome analysis revealed two major plasmid groups, IncFII/IncR and IncC, as key players in the dissemination of carbapenem resistance among carbapenem-resistant K. pneumoniae. Notably, plasmids within the same group exhibited conservation of encapsulated genes, suggesting that these plasmid groups may serve as conservative carriers of carbapenem-resistant determinants. Additionally, we investigated the evolution and expansion of IS26 integrons in carbapenem-resistant K. pneumoniae isolates using long-read sequencing. Our findings revealed the evolution and expansion of IS26 structure, which may have contributed to the development of carbapenem resistance in these strains. Our findings indicate that IncC group plasmids are associated with the endemic occurrence of carbapenem-resistant K. pneumoniae, highlighting the need for targeted interventions to control its spread. Although our study focuses on the endemic presence of carbapenem-resistant K. pneumoniae, it is important to note that carbapenem-resistant K. pneumoniae is indeed a global problem, with cases reported in multiple regions worldwide. Further research is necessary to better understand the factors driving the worldwide dissemination of carbapenem-resistant K. pneumoniae and to develop effective strategies for its prevention and control.

Diagnosis of Legionnaires' Disease Assisted by Next-Generation Sequencing in a Patient with COVID-19.

Coinfection in COVID-19 patients is associated with worsening outcome. Among patients with COVID-19, Legionella pneumophila, a common cause of pneumonia, has been reported as a co-occurring respiratory infection. A nonspecific clinical presentation, however, makes an early diagnosis difficult. Bronchoalveolar lavage fluid was collected from a patient suffering from COVID-19 and presenting with pneumonia and sent for metagenomic analysis. Differential abundance analysis was carried out by comparing each taxon reads per million between the bronchoalveolar lavage fluid sample and the negative control. Two replicates of metagenomic sequencing were conducted on bronchoalveolar lavage fluid samples. Within each replicated sequencing, one negative control was sequenced for comparison of taxon abundance in the BALF sample. In both replicates, Legionella pneumophila was the only taxon with significantly higher abundance when compared with the negative control. PCR of the bronchoalveolar further confirmed the presence of L. pneumophila. Several studies have estimated that the incidence of Legionnaires' disease co-infection in patients with COVID-19 infection is approximately 0% to 1.5%. There are some common characteristics of COVID-19 and co-infection with Legionnaires' disease, making it difficult to diagnose bacterial infection early. The diagnosis of these cases is important due to the different treatments used. Current diagnostic tests for Legionnaires' disease include conventional culture, urinary antigen for L. pneumophila serogroup 1, polymerase chain reaction, direct fluorescent antibody stain, and paired serology. The current study demonstrated that metagenomics is a promising approach that facilitated the diagnosis of Legionnaires' disease.

Identification of Cutibacterium modestum in Spondylitis by Metagenomics Analysis.

BACKGROUND/AIM: Identifying pathogens with culture-negative pyogenic spondylitis is difficult. Shotgun metagenomic sequencing is an unbiased and culture-free approach in the diagnosis of infectious diseases. There are, however, a variety of contaminating factors that can confound the precision of metagenomic sequencing. CASE REPORT: In a 65-year-old man suffering from culture-negative L3-5 spondylitis, metagenomics was applied to facilitate the diagnosis. The patient underwent percutaneous endoscopic lumbar discectomy. We applied metagenomic sequencing with a robust contamination-free protocol to the bone biopsy. By comparing the abundance for each taxon between the replicates and negative controls, we reliably identified Cutibacterium modestum as having a statistically higher abundance in all replicates. The patient's antibiotic therapy was switched to penicillin and doxycycline based upon the resistome analysis; the patient fully recovered. CONCLUSION: This application of next-generation sequencing provides a new perspective in the clinical approach to spinal osteomyelitis and illustrates the potential of this technique in rapid etiological diagnosis.

COVID-19-associated candidiasis and the emerging concern of Candida auris infections.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Bilateral Lower Limbs Cellulitis: A Narrative Review of an Overlooked Clinical Dilemma.

Bilateral lower limbs cellulitis is a rare clinical condition, which has been overlooked for a long time. In daily clinical practice, bilateral cellulitis is a sporadically encountered condition; however, it remains a clinical challenge. There is a broad differential diagnosis for this clinical entity, and there is a lack of accepted international diagnostic criteria. Unnecessary antibiotic prescription is common, which has led to an emerging problem. In this review, we summarize case reports of bilateral lower limbs cellulitis and common pathogens that have been documented.

Risk Stratification Model for Predicting Coronary Care Unit Readmission.

Background: Use of statistical models for assessing the clinical risk of readmission to medical and surgical intensive care units is well established. However, models for predicting risk of coronary care unit (CCU) readmission are rarely reported. Therefore, this study investigated the characteristics and outcomes of patients readmitted to CCU to identify risk factors for CCU readmission and to establish a scoring system for identifying patients at high risk for CCU readmission. Methods: Medical data were collected for 27,841 patients with a history of readmission to the CCU of a single multi-center healthcare provider in Taiwan during 2001-2019. Characteristics and outcomes were compared between a readmission group and a non-readmission group. Data were segmented at a 9:1 ratio for model building and validation. Results: The number of patients with a CCU readmission history after transfer to a standard care ward was 1,790 (6.4%). The eleven factors that had the strongest associations with CCU readmission were used to develop and validate a CCU readmission risk scoring and prediction model. When the model was used to predict CCU readmission, the receiver-operating curve characteristic was 0.7038 for risk score model group and 0.7181 for the validation group. A CCU readmission risk score was assigned to each patient. The patients were then stratified by risk score into low risk (0-12), moderate risk (13-31) and high risk (32-40) cohorts check scores, which showed that CCU readmission risk significantly differed among the three groups. Conclusions: This study developed a model for estimating CCU readmission risk. By using the proposed model, clinicians can improve CCU patient outcomes and medical care quality.

Metagenomic Sequencing and Histology on a Chronic Wound Identified Epstein-Barr Virus-Associated Lymphoma.

Accurate diagnosis of chronic, non-healing wounds is challenging and time-consuming because it can be caused by a variety of etiologies. This brief report presents an unusual case of a chronic wound lasting for 10 months investigated by deep metagenomic sequencing. Epstein-Barr virus (EBV) was identified in the wound and subsequently validated by in situ hybridization. Histopathologic examination eventually revealed that the non-healing wound was due to an EBV-associated NK/T cell lymphoma. By identifying mutations across the viral genome, the virus was classified as Type I EBV and clustered with others of geographic proximity. Our results suggest that metagenomic shotgun sequencing can not only rapidly and accurately identify the presence of underlying pathogens but also provide strain-level resolution for the surveillance of viral epidemiology.

Diabetes Increases Risk of Cardiovascular Events in Patients Receiving Permanent Pacemaker: A Propensity Score-Matched Cohort Study.

Background: Type 2 diabetes was associated with a higher risk for permanent pacemaker (PPM) treatment. The difference in cardiovascular outcomes between patients with and without diabetes receiving PPM treatment remains unexplored. Method: Between January 2003 and December 2017, 1742 patients receiving naïve PPM treatment comprised this retrospective cohort study and were categorized into two groups by the diagnosis of diabetes: group with diabetes (n = 632, 36.3%) and group without diabetes (n = 1110, 63.7%). The primary outcome was cardiovascular events including heart failure (HF) hospitalization and acute myocardial infarction (AMI). The secondary outcomes of this study included pacemaker infection, pacing-induced cardiomyopathy, cerebrovascular accident, cardiovascular mortality, and all-cause mortality. Propensity score matching (PSM) was applied to reduce selection bias between the study groups. Result: During a mean follow-up period of 7.8 ± 4.8 years, 264 patients had a cardiovascular event. Before PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (19.8% vs. 12.5%, P < 0.001), and the incidences of pacing-induced cardiomyopathy, cardiovascular mortality, and all-cause mortality were all higher in patients with diabetes compared to patients without diabetes. After PSM, the incidence of cardiovascular events was higher in patients with diabetes compared to patients without diabetes (18.8% vs. 12.3%, P = 0.015). The incidence of HF hospitalization was higher in patients with diabetes compared to patients without diabetes (15.3% vs. 10.2%, P = 0.037), whereas the incidence of AMI did not differ between the two groups. Moreover, after PSM, patients with diabetes had higher cumulative incidences of pacing-induced cardiomyopathy and all-cause mortality compared to patients without diabetes. Conclusions: The prevalence of diabetes was over one-third of naïve PPM recipients of this cohort, and diabetes increased the risk of cardiovascular events in PPM recipients, especially for HF hospitalization.