Genomic insights unveil the plasmid transfer mechanism and epidemiology of hypervirulent Klebsiella pneumoniae in Vietnam.

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant cause of severe invasive infections in Vietnam, yet data on its epidemiology, population structure and dynamics are scarce. We screened hvKp isolates from patients with bloodstream infections (BSIs) at a tertiary infectious diseases hospital in Vietnam and healthy individuals, followed by whole genome sequencing and plasmid analysis. Among 700 BSI-causing Kp strains, 100 (14.3%) were hvKp. Thirteen hvKp isolates were identified from 350 rectal swabs of healthy adults; none from 500 rectal swabs of healthy children. The hvKp isolates were genetically diverse, encompassing 17 sequence types (STs), predominantly ST23, ST86 and ST65. Among the 113 hvKp isolates, 14 (12.6%) carried at least one antimicrobial resistance (AMR) gene, largely mediated by IncFII, IncR, and IncA/C plasmids. Notably, the acquisition of AMR conjugative plasmids facilitated horizontal transfer of the non-conjugative virulence plasmid between K. pneumoniae strains. Phylogenetic analysis demonstrated hvKp isolates from BSIs and human carriage clustered together, suggesting a significant role of intestinal carriage in hvKp transmission. Enhanced surveillance is crucial to understand the factors driving intestinal carriage and hvKp transmission dynamics for informing preventive measures. Furthermore, we advocate the clinical use of our molecular assay for diagnosing hvKp infections to guide effective management.

Genomic characterization of Aeromonas spp. isolates from striped catfish with motile Aeromonas septicemia and human bloodstream infections in Vietnam.

Aeromonas spp. are commonly found in the aquatic environment and have been responsible for motile Aeromonas septicemia (MAS) in striped catfish, resulting in significant economic loss. These organisms also cause a range of opportunistic infections in humans with compromised immune systems. Here, we conducted a genomic investigation of 87 Aeromonas isolates derived from diseased catfish, healthy catfish and environmental water in catfish farms affected by MAS outbreaks in eight provinces in Mekong Delta (years: 2012-2022), together with 25 isolates from humans with bloodstream infections (years: 2010-2020). Genomics-based typing method precisely delineated Aeromonas species while traditional methods such as aerA PCR and MALDI-TOF were unable identify A. dhakensis. A. dhakensis was found to be more prevalent than A. hydrophila in both diseased catfish and human infections. A. dhakensis sequence type (ST) 656 followed by A. hydrophila ST251 were the predominant virulent species-lineages in diseased catfish (43.7 and 20.7 %, respectively), while diverse STs were found in humans with bloodstream infections. There was evidence of widespread transmission of ST656 and ST251 on striped catfish in the Mekong Delta region. ST656 and ST251 isolates carried a significantly higher number of acquired antimicrobial resistance (AMR) genes and virulence factors in comparison to other STs. They, however, exhibited several distinctions in key virulence factors (i.e. lack of type IV pili and enterotoxin ast in A. dhakensis), AMR genes (i.e. presence of imiH carbapenemase in A. dhakensis), and accessory gene content. To uncover potential conserved proteins of Aeromonas spp. for vaccine development, pangenome analysis has unveiled 2202 core genes between ST656 and ST251, of which 78 proteins were in either outer membrane or extracellular proteins. Our study represents one of the first genomic investigations of the species distribution, genetic landscape, and epidemiology of Aeromonas in diseased catfish and human infections in Vietnam. The emergence of antimicrobial resistant and virulent A. dhakensis strains underscores the needs of enhanced genomic surveillance and strengthening vaccine research and development in preventing Aeromonas diseases in catfish and humans, and the search for potential vaccine candidates could focus on Aeromonas core genes encoded for membrane and secreted proteins.

Implementation of remote monitoring strategies to improve chronic heart failure management.

PURPOSE OF REVIEW: The goal of this review is to describe the current evidence available for remote monitoring devices available for patients with chronic heart failure, and also detail practical clinical recommendations for implementing these tools in daily clinical practice. RECENT FINDINGS: Several devices ranging from sophisticated multiparametric algorithms in defibrillators, implantable pulmonary artery pressure sensors, and wearable devices to measure thoracic impedance can be utilized as important adjunctive tools to reduce the risk of heart failure hospitalization in patients with chronic heart failure. Pulmonary artery pressure sensors provide the most granular data regarding hemodynamic status, while alerts from wearable devices for thoracic impedance and defibrillator-based algorithms increase the likelihood of worsening clinical status while also having high negative predictive value when values are within normal range. SUMMARY: Multiple device-based monitoring strategies are available to reduce longitudinal risk in patients with chronic heart failure. Further studies are needed to best understand a practical pathway to integrate multiple signals of data for early clinical decompensation risk predictionVideo abstract: http://links.lww.com/HCO/A95.

Elucidating the Paradox of Regulating Environmental Sustainability (Mis)management and Motivations: The Case of Thai Fisheries.

This article introduces and elucidates a new sustainability management paradox by examining the difficulties of applying the European Union's illegal, unreported and unregulated (IUU) fishing regulations in Thai waters. Interviews were conducted with key stakeholders of Thailand's fishery sector to explore the particularities of the area. Configuration theory-from a strategic management perspective-was used to guide empirical research and extend it to the context of environmental regulation. The research finds that when it makes more business sense for stakeholders to engage in sustainability matters, more explicit engagement might take place of the wrong type, but the true sustainability objectives become performed more poorly and mismanaged, perhaps resulting in a worse-off position than started with. This is because regulation is astute at setting targets, but ineffective at engaging with key stakeholders. A composite model of how configuration theory fits within discussions of sustainability motivations is posited as the theoretical contribution to knowledge.

Mitochondrial H2S Regulates BCAA Catabolism in Heart Failure.

BACKGROUND: Hydrogen sulfide (H2S) exerts mitochondria-specific actions that include the preservation of oxidative phosphorylation, biogenesis, and ATP synthesis, while inhibiting cell death. 3-MST (3-mercaptopyruvate sulfurtransferase) is a mitochondrial H2S-producing enzyme whose functions in the cardiovascular disease are not fully understood. In the current study, we investigated the effects of global 3-MST deficiency in the setting of pressure overload-induced heart failure. METHODS: Human myocardial samples obtained from patients with heart failure undergoing cardiac surgeries were probed for 3-MST protein expression. 3-MST knockout mice and C57BL/6J wild-type mice were subjected to transverse aortic constriction to induce pressure overload heart failure with reduced ejection fraction. Cardiac structure and function, vascular reactivity, exercise performance, mitochondrial respiration, and ATP synthesis efficiency were assessed. In addition, untargeted metabolomics were utilized to identify key pathways altered by 3-MST deficiency. RESULTS: Myocardial 3-MST was significantly reduced in patients with heart failure compared with nonfailing controls. 3-MST KO mice exhibited increased accumulation of branched-chain amino acids in the myocardium, which was associated with reduced mitochondrial respiration and ATP synthesis, exacerbated cardiac and vascular dysfunction, and worsened exercise performance following transverse aortic constriction. Restoring myocardial branched-chain amino acid catabolism with 3,6-dichlorobenzo1[b]thiophene-2-carboxylic acid (BT2) and administration of a potent H2S donor JK-1 ameliorates the detrimental effects of 3-MST deficiency in heart failure with reduced ejection fraction. CONCLUSIONS: Our data suggest that 3-MST derived mitochondrial H2S may play a regulatory role in branched-chain amino acid catabolism and mediate critical cardiovascular protection in heart failure.

De novo human leukocyte antigen allosensitization patterns in patients bridged to heart transplantation using left ventricular assist devices.

INTRODUCTION: We examined the impact and time course of de novo human leukocyte antigen (HLA) allosensitization following left ventricular assist device (LVAD) implantation. METHODS AND RESULTS: Forty patients had a calculated panel reactive antibody (cPRA) prior to LVAD surgery between January 2014 and December 2018. Of these patients, we retrospectively studied 33 patients who had pre-LVAD cPRA <10%. De novo allosensitization was defined as cPRA ≥10% within 3 months following LVAD surgery, and "persistent allosensitization" was defined as cPRA ≥10% at time of heart transplant or death. One-third (11/33) of our cohort developed de novo allosensitization within 3-months post-LVAD. Median duration of follow-up during LVAD support was 588 days (IQR 337-1071 days), or approximately 19 months. In an adjusted, multivariable analysis, female sex remained associated with de novo allosensitization (adjusted odds ratio [95%CI]: 11 (1.4-85), P = 0.026). De novo allosensitization was subsequently associated with persistent allosensitization (P = 0.024). Both axial-flow and centrifugal-flow LVADs had similar rates of allosensitization. Compared to those with no allosensitization, patients with de novo allosensitization did not appear to have inferior post-transplant outcomes of death or treated rejection. CONCLUSION: In our single-center experience, one-third of patients developed de novo allosensitization which did not appear to associate with inferior post-transplant outcomes. Female sex was associated with de novo allosensitization.

Genomic insights into the circulation of pandemic fluoroquinolone-resistant extra-intestinal pathogenic Escherichia coli ST1193 in Vietnam.

Extra-intestinal pathogenic Escherichia coli (ExPEC) ST1193, a globally emergent fluoroquinolone-resistant clone, has become an important cause of bloodstream infections (BSIs) associated with significant morbidity and mortality. Previous studies have reported the emergence of fluoroquinolone-resistant ExPEC ST1193 in Vietnam; however, limited data exist regarding the genetic structure, antimicrobial resistance (AMR) determinants and transmission dynamics of this pandemic clone. Here, we performed genomic and phylogenetic analyses of 46 ST1193 isolates obtained from BSIs and healthy individuals in Ho Chi Minh City, Vietnam, to investigate the pathogen population structure, molecular mechanisms of AMR and potential transmission patterns. We further examined the phylogenetic structure of ST1193 isolates in a global context. We found that the endemic E. coli ST1193 population was heterogeneous and highly dynamic, largely driven by multiple strain importations. Several well-supported phylogenetic clusters (C1-C6) were identified and associated with distinct blaCTX-M variants, including blaCTXM-27 (C1-C3, C5), blaCTXM-55 (C4) and blaCTXM-15 (C6). Most ST1193 isolates were multidrug-resistant and carried an extensive array of AMR genes. ST1193 isolates also exhibited the ability to acquire further resistance while circulating in Vietnam. There were phylogenetic links between ST1193 isolates from BSIs and healthy individuals, suggesting these organisms may both establish long-term colonization in the human intestinal tract and induce infections. Our study uncovers factors shaping the population structure and transmission dynamics of multidrug-resistant ST1193 in Vietnam, and highlights the urgent need for local One Health genomic surveillance to capture new emerging ExPEC clones and to better understand the origins and transmission patterns of these pathogens.

Impact of COVID-19 on Patients Supported with a Left Ventricular Assist Device.

Patients on left ventricular assist device (LVAD) support may be susceptible to severe disease and complications from coronavirus disease-19 (COVID-19). The purpose of this study was to describe the clinical course of COVID-19 in LVAD patients. A retrospective review was performed at our center; 28 LVAD patients who developed COVID-19 between March 2020 and March 2021, and six patients with a prior COVID-19 infection who underwent LVAD implantation, were identified and examined. Of the 28 patients, nine (32%) died during the study period, five (18%) during their index hospitalization for COVID-19. Two patients (7%) presented with suspected pump thrombosis. In a nonadjusted binary regression logistic analysis, admission to the intensive care unit (unadjusted odds ratio, 7.6 [CI, 1.2-48], P = 0.03), and the need for mechanical ventilation (unadjusted odds ratio 14 [CI, 1.3-159], P = 0.03) were associated with mortality. The six patients who previously had COVID-19 and subsequently received a LVAD were on intra-aortic balloon pump and inotropic support at time of surgery. All six experienced a complicated and prolonged postoperative course. Three patients (50%) suffered from ischemic stroke, and there was one (17%) 30 day mortality. We observed an increased risk of morbidity and mortality in LVAD patients with COVID-19.

Troubleshooting Total Artificial Heart: Novel Use of Implantable Hemodynamic Monitor.

Accurate device optimization of the Syncardia temporary total artificial heart is difficult while waiting for heart transplantation. In this challenging clinical cohort, using an implantable hemodynamic monitor (CardioMEMS HF system) can assist in volume and hemodynamic assessments. (Level of Difficulty: Advanced.).

Powerlifting score prediction using a machine learning method.

This research discusses an interesting topic, using artificial intelligence methods to predict the score of powerlifters. We collected the characteristics of powerlifters, and then used the reservoir computing extreme learning machine to build a predictive model. In order to further improve the prediction results, we propose a method to optimize the reservoir computing extreme learning machine using the whale optimization algorithm. Experimental results show that our proposed method can effectively predict the score of powerlifters with the coefficient of determination value is 0.7958 and root-mean-square error of prediction value is 16.73. This provides a reliable basis for experts to judge the results before the competition.

The First 100 Days of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Control in Vietnam.

BACKGROUND: One hundred days after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Vietnam on 23 January, 270 cases were confirmed, with no deaths. We describe the control measures used by the government and their relationship with imported and domestically acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control. METHODS: Clinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of government control measures, including numbers of tests and quarantined individuals, were analyzed. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of presymptomatic transmission events and time-varying reproduction numbers. RESULTS: A national lockdown was implemented between 1 and 22 April. Around 200 000 people were quarantined and 266 122 reverse transcription polymerase chain reaction (RT-PCR) tests conducted. Population mobility decreased progressively before lockdown. In total, 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. The serial interval was 3.24 days, and 27.5% (95% confidence interval [CI], 15.7%-40.0%) of transmissions occurred presymptomatically. Limited transmission amounted to a maximum reproduction number of 1.15 (95% CI, .·37-2.·36). No community transmission has been detected since 15 April. CONCLUSIONS: Vietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial presymptomatic transmission.

Rapid Deterioration of Hospital-Acquired COVID-19 in a Patient on Extracorporeal Left Ventricular Assist Support.

IMPORTANCE: As the Coronavirus disease 2019 (COVID-19) pandemic accelerates, our hospitals have become overwhelmed. OBJECTIVE: To describe detection of COVID-19 in asymptomatic hospitalized individuals awaiting advanced therapies for HF and the management of complications of COVID-19. DESIGN: We present a unique case report of hospital-acquired COVID-19 in a patient on temporary mechanical circulatory support. MAIN OUTCOME: Despite intensive care and monitoring, he developed rapid progression of hypoxic respiratory failure which led to his death. CONCLUSION: This case highlights various considerations for a patient with temporary MCS. It illustrates the high risk for development of COVID-19 for vulnerable hospitalized patients.

Predisposition or Protection?: COVID-19 in a Patient on LVAD Support With HIV/AIDS.

There is a desperate search to discover effective therapies against coronavirus disease-2019 (COVID-19). Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) comprise a unique population whose clinical course may provide insights into the effects of antiretroviral therapy on COVID-19. We describe the case of a patient with HIV/AIDS on left ventricular assist device support who was hospitalized and recovered from COVID-19. (Level of Difficulty: Intermediate.).

Elevated AT1R Antibody and Morbidity in Patients Bridged to Heart Transplant Using Continuous Flow Left Ventricular Assist Devices.

BACKGROUND: We studied longitudinal levels of angiotensin-II type 1 receptor antibody (AT1R-Ab) and their effects on adverse events (death, treated rejection and cardiac allograft vasculopathy) in patients who were bridged to heart transplant using a continuous flow left ventricular assist device (LVAD). METHODS AND RESULTS: Sera of 77 patients bridged to heart transplant (from 2009 to 2017) were tested for AT1R-Ab and CRP before and after LVAD. Elevated AT1R-Ab was defined as >10.0 U/mL. The median follow-up after transplant was 3.6 years (interquartile range, 2.2-5.6 years). After LVAD, AT1R-Ab levels increased from baseline and remained elevated until transplant. Freedom from adverse events at 5 years was lower in those with elevated AT1R-Ab levels at time of transplant. In an adjusted, multivariable Cox analysis, an AT1R-Ab level of >10 U/mL was associated with developing the primary end point (adjusted hazard ratio 3.4, 95% confidence interval 1.2-9.2, P = .017). Although C-reactive protein levels were high before and after LVAD placement, C-reactive protein did not correlate with AT1R-Ab. CONCLUSIONS: In LVAD patients bridged to heart transplant, an increased AT1R-Ab level at time of transplant was associated with poor outcomes after heart transplant. Post-LVAD AT1R-Ab elevations were not correlated with serum markers of systemic inflammation. Larger studies are needed to examine the pathologic role of AT1R-Ab in heart transplant.

Hydrogen Sulfide Therapy Suppresses Cofilin-2 and Attenuates Ischemic Heart Failure in a Mouse Model of Myocardial Infarction.

AIMS: Hydrogen sulfide (H2S) protects against ischemic and inflammatory injury following myocardial ischemia via induction of microRNA (miR)-21. We sought to determine whether H2S attenuates ischemic heart failure with reduced ejection fraction (HFrEF) and interrogate the role of cofilin-2, a target of miR-21, in this protective process. METHODS AND RESULTS: Adult male mice underwent myocardial infarction (MI) by coronary artery ligation after baseline echocardiography. Following MI, mice were treated with Na2S (100 µg/kg/day; intraperitoneal [IP]) or saline up to 28 days. End-diastolic pressure, measured by Millar catheter, was significantly increased (P < .05 vs sham) at 3 days post-MI in the saline group, which was attenuated with Na2S. Left ventricular (LV) fractional shortening decreased significantly at 28 days post-MI in the saline group but was preserved with Na2S and LV infarct scar size was smaller in Na2S group as compared to control. Apoptotic signaling, measured by Bcl-2/Bax ratio, was significantly increased in the saline group but was mitigated with Na2S. Survival rate was 2-fold higher in Na2S group compared to saline control (P < .05). Proteomic analysis and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (TOF)/TOF tandem mass spectrometry identified significant changes in proapoptotic cofilin-2 expression, a specific target of miR-21, between saline- and sodium sulfide -treated mice at 28 days post-MI. Western blot analysis confirmed a significant increase in cofilin-2 after MI, which was suppressed with Na2S treatment. Chronic Na2S treatment also attenuated inflammasome formation and activation leading to reduction of maladaptive signaling. CONCLUSION: Na2S treatment after MI preserves LV function and improves survival through attenuation of inflammasome-mediated adverse remodeling. We propose H2S donors as promising therapeutic tools for ischemic HFrEF.

The first 100 days of SARS-CoV-2 control in Vietnam

BackgroundOne hundred days after SARS-CoV-2 was first reported in Vietnam on January 23rd, 270 cases have been confirmed, with no deaths. We describe the control measures used by the Government and their relationship with imported and domestically-acquired case numbers, with the aim of identifying the measures associated with successful SARS-CoV-2 control. MethodsClinical and demographic data on the first 270 SARS-CoV-2 infected cases and the timing and nature of Government control measures, including numbers of tests and quarantined individuals, were captured by Vietnams National Steering Committee for COVID-19 response. Apple and Google mobility data provided proxies for population movement. Serial intervals were calculated from 33 infector-infectee pairs and used to estimate the proportion of pre-symptomatic transmission events and time-varying reproduction numbers. FindingsAfter the first confirmed case on January 23rd, the Vietnamese Government initiated mass communications measures, case-contact tracing, mandatory 14-day quarantine, school and university closures, and progressive flight restrictions. A national lockdown was implemented between April 1st and 22nd. Around 200 000 people were quarantined and 266 122 RT-PCR tests conducted. Population mobility decreased progressively before lockdown. 60% (163/270) of cases were imported; 43% (89/208) of resolved infections remained asymptomatic for the duration of infection. 21 developed severe disease, with no deaths. The serial interval was 3.24 days, and 27.5% (95% confidence interval, 15.7%-40.0%) of transmissions occurred pre-symptomatically. Limited transmission amounted to a maximum reproduction number of 1.15 (95% confidence interval, 0.37-2.36). No community transmission has been detected since April 15th. InterpretationVietnam has controlled SARS-CoV-2 spread through the early introduction of mass communication, meticulous contact-tracing with strict quarantine, and international travel restrictions. The value of these interventions is supported by the high proportion of asymptomatic and imported cases, and evidence for substantial pre-symptomatic transmission. FundingThe Vietnam Ministry of Health and Wellcome Trust, UK. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVietnam was one of the first countries outside of China to detect imported and human-to-human transmitted SARS-CoV-2 within its borders. Yet, as of May 1st, a total of only 270 cases have been confirmed, no deaths have occurred, and no community transmission has been detected since April 15th despite intensive screening, tracing and testing. We did a PubMed database search to identify studies investigating COVID-19 response in Vietnam using the terms "Vietnam", "COVID-19", and "SARS-CoV-2". All relevant articles were evaluated. Studies describe cases of COVID-19 and their management, aspects of the government response from newspapers and online government sources, but there are no previous reports using national data to describe and investigate the national epidemic and the impact of control measures cases over time. Added value of this studyWe used data from the National Steering Committee for COVID-19 response to give a comprehensive account of the first 100 days of the SARS-CoV-2 epidemic in Vietnam, including case numbers and their symptomatology, the estimated reproductive number by week, and their relation to the multiple control measures instituted by the Vietnam Government over time. We show two distinctive features of Vietnams response. First, the Government took rapid actions to restrict international flights, closed schools and universities, and instituted meticulous case-contact tracing and quarantining from late January, well before these measures were advised by WHO. Second, they placed mass communication, education, and the identification, serial testing, and 14-day quarantine of all direct contacts of cases, regardless of symptom development, at the heart of the response. The value of strict contact-tracing and quarantine is supported by the high proportion of asymptomatic cases (43%) and imported cases (60%), and evidence for substantial pre-symptomatic transmission. Implications of all the available evidenceVietnam has had remarkable success in controlling the emergence of SARS-CoV-2. Our report provides a complete picture of the control of SARS-CoV-2 in Vietnam, with lessons for other Governments seeking to extend national SARS-CoV-2 control or prevent future epidemics. Our findings shows the importance of acting early, before the virus becomes established in the community, and before the case numbers overwhelm systems of case-contact tracing and mass quarantine. They also demonstrate the value of effective mass communication in rapidly educating the public in infection prevention measures and providing real-time information on the state of the epidemic.

The Imperfect Cytokine Storm: Severe COVID-19 With ARDS in a Patient on Durable LVAD Support.

As health systems worldwide grapple with the coronavirus disease-2019 (COVID-19) pandemic, patients with durable LVAD support represent a unique population at risk for the disease. This paper outlines the case of such a patient who developed COVID-19 complicated by a "cytokine storm" with severe acute respiratory distress syndrome and myocardial injury and describes the challenges that arose during management.