Risk factors and outcome associated with coinfection with carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumanii: a descriptive analysis.

Background: Nearly 30% of patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) were previously shown to be coinfected with carbapenem-resistant Pseudomonas aeruginosa (CRPA) or Acinetobacter baumannii (CRAB). Infections caused by multiple carbapenem-resistant pathogens present significant challenge to infection control and therapeutic management. The study objective was to identify risk factors for acquisition of multiple carbapenem-resistant pathogens and associated outcomes. Methods: A descriptive analysis of adults infected with either CRKP alone or coinfected with CRPA or CRAB was performed. Patient groups were compared on demographics, clinical characteristics, treatment, and outcome. Results: 86 patients with CRKP monoinfection and 60 patients with coinfections were evaluated. Respiratory tract was the predominant infection site for coinfected patients involving mostly CRPA whereas urinary tract was the primary site for CRKP-only group. More coinfected patients were severely debilitated, had prior carbapenem exposure (37% vs 13%, p<0.001) and history of pneumonia in the past year (67% vs 41%, p<0.01). More coinfected patients required direct ICU admission (45% vs 27%, p=0.02) and had prolonged length of stay (median 15 vs 10 days, p<0.01) than the CRKP-only group but mortality rates (18% vs 16%) were similar. Conclusions: CRKP coinfection with another carbapenem-resistant pathogen adds significant morbidity and healthcare burden overall. Empiric therapy with reliable activity against both CRKP and carbapenem-resistant Pseudomonas aeruginosa may be prudent for at risk patients with pneumonia.

Factors associated with prompt recovery among hospitalised patients with coronavirus disease 2019.

BACKGROUND: Patients who survived hospitalisation for COVID-19 experienced varying durations of illness but the factors associated with prompt recovery are unknown. This study identifies factors differentiating hospitalised patients who recovered promptly versus survived a prolonged course of illness because of COVID-19. METHODS: This was a retrospective study from March-August 2020 of hospitalised adults with COVID-19 which were grouped based on time to recovery: short (≤3 days), intermediate (4-10 days) and prolonged (>10 days). Recovery was defined as resolution of fever, tachypnea, hypotension, extubation and return of mental status at baseline. Multivariate analysis was used to evaluate factors associated with prompt recovery. RESULTS: Among 508 patients hospitalised for COVID-19, 401 (79%) survived. Of those, prompt recovery (within 3 days) was achieved in 43% (174/401), whereas 23% (92/401) recovered after a prolonged period of >10 days. Overall, median age was 64 years with 73% admitted from home and 25% from a skilled nursing facility. Predictors for prompt recovery upon admission included female sex (OR, 1.8; 95% CI, 1.1-2.7; P = .01), no fever (OR, 1.6; 95% CI, 1.1-2.6; P = .03), longer time from symptom onset to hospitalisation (OR, 1.1; 95% CI, 1.0-1.1; P = .001), no supplemental oxygen (OR, 1.9; 95% CI, 1.2-3.0; P = .004), no direct ICU admission (OR, 41.7; 95% CI, 2.4-740.4; P = .01) and absence of bacterial co-infections (OR, 2.5; 95% CI, 1.5-4.0, P = .0003). CONCLUSIONS: Our study provides relevant data that could help clinicians triage competing resources in health systems that are challenged by the ebb and flow of COVID-19 cases by identifying clinical features of COVID-19 patients who may require less intensive management including avoidance of unnecessary antibacterial therapy.

Risk factors and outcome associated with infection or colonization due to carbapenem-heteroresistant Escherichia coli.

BACKGROUND: Up to 32% of ESBL-producing Enterobacterales strains display a carbapenem-heteroresistant (cHR) phenotype but its clinical relevance is unknown. OBJECTIVES: To determine risk factors and clinical outcome associated with infection due to cHR ESBL-producing Escherichia coli (ESBL-EC). METHODS: A retrospective, case-control study was conducted on patients from whom a pair of clonally related E. coli strains were isolated during separate healthcare encounters with (case) or without (control) development of cHR phenotype in the latter strain. Study groups were compared for host and microbial characteristics and carbapenem exposure. Outcome measures included ICU admission, length of hospitalization, and mortality. RESULTS: Study patients (15 cases, 10 controls) were elderly (median age: 74 years) with half admitted from home (52%), most (80%) having ≥3 comorbid conditions and severe functional impairment. Case patients were more likely to have 'index' ESBL-EC isolating from blood (27% versus 0%; P = 0.125) and have greater cumulative amount and duration of carbapenem exposure than controls. All control 'subsequent' isolates were from urine whereas five cHR case isolates were from blood or respiratory sources. More hospitalized case patients required ICU admission (23% versus 0%; P = 0.257) and prolonged hospital stay (>7 days) than controls (62% versus 38%%; P = 0.387). CONCLUSIONS: Our findings deserve confirmation with a larger study population and call attention to the potential for increased morbidity with cHR ESBL-EC infections, which underscores the need to screen for cHR phenotype in patients with repeated growth of ESBL-EC, particularly from systemic sites and patients that have had extensive carbapenem exposure.

Development and specification of GABAergic cortical interneurons.

GABAergic interneurons are inhibitory neurons of the nervous system that play a vital role in neural circuitry and activity. They are so named due to their release of the neurotransmitter gamma-aminobutyric acid (GABA), and occupy different areas of the brain. This review will focus primarily on GABAergic interneurons of the mammalian cerebral cortex from a developmental standpoint. There is a diverse amount of cortical interneuronal subtypes that may be categorized by a number of characteristics; this review will classify them largely by the protein markers they express. The developmental origins of GABAergic interneurons will be discussed, as well as factors that influence the complex migration routes that these interneurons must take in order to ultimately localize in the cerebral cortex where they will integrate with the neural circuitry set in place. This review will also place an emphasis on the transcriptional network of genes that play a role in the specification and maintenance of GABAergic interneuron fate. Gaining an understanding of the different aspects of cortical interneuron development and specification, especially in humans, has many useful clinical applications that may serve to treat various neurological disorders linked to alterations in interneuron populations.

Uncovering the link between malfunctions in Drosophila neuroblast asymmetric cell division and tumorigenesis.

Asymmetric cell division is a developmental process utilized by several organisms. On the most basic level, an asymmetric division produces two daughter cells, each possessing a different identity or fate. Drosophila melanogaster progenitor cells, referred to as neuroblasts, undergo asymmetric division to produce a daughter neuroblast and another cell known as a ganglion mother cell (GMC). There are several features of asymmetric division in Drosophila that make it a very complex process, and these aspects will be discussed at length. The cell fate determinants that play a role in specifying daughter cell fate, as well as the mechanisms behind setting up cortical polarity within neuroblasts, have proved to be essential to ensuring that neurogenesis occurs properly. The role that mitotic spindle orientation plays in coordinating asymmetric division, as well as how cell cycle regulators influence asymmetric division machinery, will also be addressed. Most significantly, malfunctions during asymmetric cell division have shown to be causally linked with neoplastic growth and tumor formation. Therefore, it is imperative that the developmental repercussions as a result of asymmetric cell division gone awry be understood.

WOX2 and STIMPY-LIKE/WOX8 promote cotyledon boundary formation in Arabidopsis.

One of the key events in dicot plant embryogenesis is the emergence of the two cotyledon primordia, which marks the transition from radial symmetry to bilateral symmetry. In Arabidopsis thaliana, the three CUP-SHAPED COTYLEDON (CUC) genes are responsible for determining the boundary region between the cotyledons. However, the mechanisms controlling their transcription activation are not well understood. Previous studies found that several WOX family homeobox transcription factors are involved in embryo apical patterning and cotyledon development. Here we show that WOX2 and STIMPY-LIKE (STPL/WOX8) act redundantly to differentially regulate the expression of the CUC genes in promoting the establishment of the cotyledon boundary, without affecting the primary shoot meristem. Loss of both WOX2 and STPL results in reduced CUC2 and CUC3 expression in one side of the embryo, but an expansion of the CUC1 domain. Furthermore, we found that STPL is expressed in the embryo proper, and its activation is enhanced by the removal of WOX2, providing an explanation for the functional redundancy between WOX2 and STPL. Additional evidence also showed that WOX2 and STPL function independently in regulating different aspects of local auxin gradient formation during early embryogenesis.