Outcomes and characteristics of ertapenem-nonsusceptible Klebsiella pneumoniae bacteremia at a university hospital in Northern Taiwan: A matched case-control study

Background and purposeCarbapenem-resistant Klebsiella pneumoniae is an emerging problem worldwide. The object of this study was to investigate the risk factors, characteristics and outcomes of ertapenem-nonsusceptible K pneumoniae (ENSKp) bacteremia.MethodsWe conducted a 1:2 ratio matched case-control study. The controls were randomly selected among patients with ertapenem-susceptible K pneumoniae (ESKp) bacteremia and were matched with ENSKp cases for bacteremia.ResultsSeventy-five patients were included in this study (25 cases and 50 controls). Bivariate analysis showed that prior exposure to either β-Lactam/β-Lactam-lactamase inhibitors (p = 0.008) or 4th generation cephalosporins (p < 0.001), chronic obstructive pulmonary disease (COPD) (p = 0.001), acute renal failure (p = 0.021), chronic kidney disease without dialysis (p = 0.021), recent hospital stay (p = 0.016), intensive care unit stay (p = 0.002), mechanical ventilation (p = 0.003), central venous catheter placement (p = 0.016), Foley indwelling (p = 0.022), polymicrobial bacteremia (p = 0.003) and higher Pittsburgh bacteremia score (p < 0.001) were associated with ENSKp bacteremia. The multivariate analysis showed that prior exposure to 4th generation cephalosporins (odds ratio [OR], 28.05; 95% confidence interval [CI], 2.92–269.85; p = 0.004), COPD (OR, 21.38; 95% CI, 2.95–154.92; p = 0.002) and higher Pittsburgh bacteremia score (OR, 1.35; 95% CI, 1.10–1.66; p = 0.004) were independent factors for ENSKp bacteremia. ENSKp bacteremia had a higher 14-day mortality rate than ESKp bacteremia (44.0% vs. 22.0%; p = 0.049). The overall in-hospital mortality rates for these two groups were 60.0% and 40.0% respectively (p = 0.102).ConclusionENSKp bacteremia had a poor outcome and the risk factors were prior exposure of 4th generation cephalosporins, COPD and higher Pittsburgh bacteremia score. Antibiotic stewardship may be the solution for the preventive strategy

Risk factors and outcomes of carbapenem-nonsusceptible Escherichia coli bacteremia: A matched case–control study

BackgroundInfections due to carbapenem-resistant Enterobacteriaceae have been the emerging problem worldwide. This primary object of this study was to understand the risk factors and clinical outcomes of carbapenem-nonsusceptible Escherichia coli (CNSEc) bacteremia.MethodsWe conducted a matched case–control study in a 3,715-bed tertiary care medical center in northern Taiwan. The controls were selected among patients with carbapenem-susceptible E coli and were matched with CNSEc for bacteremia.ResultsFifty-one patients were included in this study (17 cases and 34 controls). Bivariate analysis showed that prior exposure to carbapenems (p<0.001), stay in intensive care units (p=0.016), placement of central venous catheters (p=0.001), chronic liver diseases (p<0.001), uremia with regular dialysis (p=0.004), and mechanical ventilation (p=0.004) were associated with CNSEc bacteremia. Multivariate analysis revealed that prior exposure to carbapenems [odds ratio (OR), 29.17; 95% confidence interval (CI), 1.76–484.70; p=0.019], uremia with regular dialysis (OR, 98.58; 95% CI, 4.02–999; p=0.005) and chronic liver diseases (OR, 27.86; 95% CI, 2.31–335.83; p=0.009) were independent risk factors for CNSEc bacteremia. Compared with carbapenem-susceptible E coli group, CNSEc group had a longer hospital stay (68.4 days vs. 35.8 days; p=0.04) and a higher disease severity, as indicated by a Pittsburgh bacteremia score greater than or equal to 4 (5.6% vs. 2.5%; p=0.015). Patients with CNSEc bacteremia had a higher overall in-hospital mortality rate (94.12% vs. 50.00%; p=0.002), but there was no difference in the 28-day mortality between these two groups.ConclusionsCNSEc bacteremia would lead to a poor outcome among patients with prior exposure to carbapenems, chronic liver disease, and uremia with regular dialysis

Risk factors and clinical significance of bacteremia caused by Pseudomonas aeruginosa resistant only to carbapenems

Background/purposeCarbapenem-resistant Pseudomonas aeruginosa infections have been a challenge and issue in hospital settings. However, the clinical impact of P. aeruginosa blood isolates resistant only to carbapenems has never been discussed previously.MethodsTo assess the risk factors and clinical significance of bacteremia caused by carbapenem resistance only P. aeruginosa (CROPA), a 6-year retrospective case–control study was conducted. The CROPA strains were defined as isolates susceptible to ciprofloxacin, antipseudomonal penicillins and cephalosporins, and aminoglycosides but resistant to one antipseudomonal carbapenem (imipenem or meropenem) or both. The controls were selected among patients with bacteremia due to P. aeruginosa susceptible to all above classes of antipseudomonal antibiotics, which was defined as all-susceptible P. aeruginosa.ResultsTwenty-five patients had at least one blood culture positive for CROPA, and 50 controls had all-susceptible P. aeruginosa bacteremia. CROPA bacteremia had a high 30-day mortality rate (72.0%), as compared to 26.0% for the controls (p < 0.001). Through multivariate analysis, carbapenem exposure was the only risk factor for developing CROPA bacteremia (p = 0.002). A comparison between the surviving and deceased patients with CROPA bacteremia showed that nine (50%) of those who died, but none of the survivors, received carbapenems as the initial empirical therapy (p = 0.027).ConclusionCarbapenem exposure was associated with emergence of CROPA infections. Repeated carbapenem use in such patients might increase rates of inappropriate initial empirical treatment and mortality. Prudent carbapenem use is important to reduce the emergence of CROPA

A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (\u3e105 copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced viral yield and viral protein synthesis. We also present evidence that vsRNA1 targets stem-loop II of the viral 5′ untranslated region and inhibits the activity of the IRES through this sequence-specific targeting. Our study demonstrates the ability of a cytoplasmic RNA virus to generate functional vsRNA in mammalian cells. In addition, we also demonstrate a potential novel mechanism for a positive-stranded RNA virus to regulate viral translation: generating a vsRNA that targets the IRES

Where are the missing people affected by tuberculosis? A programme review of patient-pathway and cascade of care to optimise tuberculosis case-finding, treatment and prevention in Cambodia.

BACKGROUND: Cambodia has achieved great success in tuberculosis (TB) control in the past decade. Nevertheless, people with TB are missed by the health systems at different stages of the care pathway. This programme review corroborated the care-seeking behaviours of people with TB and TB services availability and estimated the number of people completing each step of the TB disease and TB preventive treatment (TPT) care cascade. METHODS: Patient pathways and the care cascades for TB disease and TPT were constructed using data from the latest national TB prevalence survey, routine surveillance and programme, the global TB database and published studies. We also randomly selected TB survivors in the 2019 cohort to assess recurrence-free survival 1-year post-treatment. TPT care cascade was constructed for people living with HIV (PLHIV) and household contacts (children <5 years and all ages) of persons with bacteriologically-confirmed TB in 2019 and 2020. RESULTS: Nationally, 54% of those who exhibited TB symptoms sought initial care in the private sector. Overall, 93% and 58% of people with presumptive TB did not access a facility with TB diagnostic and treatment services, respectively, at the first point of care-seeking. Approximately 56% (95% CI 52% to 57%) of the 47 000 (95% CI 31 000 to 68 000) estimated TB cases in 2019 achieved recurrence-free survival. Among the estimated PLHIV in Cambodia, <30% completed TPT. Among children <5 years, 53% (95% CI 29% to 65%) (2019) and 67% (95% CI 36% to 80%) (2020) of those eligible for TPT completed the regimen successfully. In 2019 and 2020, 23% (95% CI 22% to 25%) and 54% (95% CI 50% to 58%) of the estimated household contacts (all ages) eligible for TPT completed the regimen successfully. CONCLUSION: There are significant gaps in care-seeking, coverage and access to TB services and TPT in Cambodia. Action plans to improve TB response have been co-developed with local stakeholders to address the gaps throughout the care cascades

Foxp2 controls synaptic wiring of corticostriatal circuits and vocal communication by opposing Mef2c

Cortico-basal ganglia circuits are critical for speech and language and are implicated in autism spectrum disorder, in which language function can be severely affected. We demonstrate that in the mouse striatum, the gene Foxp2 negatively interacts with the synapse suppressor gene Mef2c. We present causal evidence that Mef2c inhibition by Foxp2 in neonatal mouse striatum controls synaptogenesis of corticostriatal inputs and vocalization in neonates. Mef2c suppresses corticostriatal synapse formation and striatal spinogenesis, but can itself be repressed by Foxp2 through direct DNA binding. Foxp2 deletion de-represses Mef2c, and both intrastriatal and global decrease of Mef2c rescue vocalization and striatal spinogenesis defects of Foxp2-deletion mutants. These findings suggest that Foxp2-Mef2C signaling is critical to corticostriatal circuit formation. If found in humans, such signaling defects could contribute to a range of neurologic and neuropsychiatric disorders.National Institutes of Health (U.S.) (Grant R37 HD028341)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award R37 HD028341

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO