Daily Sepsis Research Analysis

BACKGROUND: Kangaroo care has a well-established role in preterm infant stabilisation and in protecting low-birthweight newborns from mortality. Yet kangaroo care is far from fully embedded in conventional inpatient neonatal care practice. The evidence on infection outcomes of hospital-initiated kangaroo care is unclear. We aimed to evaluate the existing evidence to understand the role of hospital-initiated kangaroo care in preventing mortality, sepsis, and invasive infection in low-birthweight infants. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, Cochrane Library, and Web of Science databases for literature published between Jan 1, 2013, and Feb 26, 2025. At least two authors independently undertook study selection, data extraction, and quality assessment. Reports of randomised controlled trials presenting data on at least one of our set primary outcomes (all-cause mortality and/or sepsis and/or invasive infection) comparing kangaroo care with conventional neonatal care in low-birthweight infants (<2500 g) were eligible for inclusion. The primary outcomes were all-cause mortality, sepsis, and invasive infection (composite of necrotising enterocolitis, pneumonia, meningitis, and other severe infections). Hypothermia and apnoea were assessed as adverse events. A random effects model was used to estimate the pooled overall effect sizes for each outcome, presented as odds ratios (OR [95% CI]), with between-study heterogeneity assessed by Cochran's Q test and sources of heterogeneity investigated using univariable random effects meta-regression analyses. This study is registered with PROSPERO, CRD42024501546. FINDINGS: We synthesised data from 29 studies, mainly from lower-middle income countries, including 17 513 low-birthweight infants. Most studies were moderate-to-high quality. 25 (86%) of 29 studies reporting all-cause mortality were included in the meta-analysis of hospital-initiated kangaroo care, which showed that hospital-initiated kangaroo care reduced all-cause mortality (pooled OR 0·77 [95% CI 0·67-0·89]; high-quality evidence, with I

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.

BACKGROUND: Sepsis, a critical organ dysfunction resulting from an aberrant host response to infection, remains a leading cause of mortality in ICU patients. Recent evidence suggests that angiotensin-converting enzyme 2 (ACE2) contributes to intestinal barrier function, the mechanism of which is yet to be explored. Additionally, alterations in intestinal microbiota and microbial metabolites could affect gut homeostasis, thus playing a potential role in modulating sepsis progression. RESULTS: ACE2 shedding weakens the integrity of the intestinal barrier in sepsis. Mice deficient in ACE2 exhibited increased intestinal permeability and higher mortality rates post-operation compared to their wild-type counterparts. Notably, ACE2 deficiency was associated with distinct alterations in gut microbiota composition and reductions in protective metabolites, such as 5-methoxytryptophan (5-MTP). Supplementing septic mice with 5-MTP ameliorated gut leak through enhanced epithelial cell proliferation and repair. The PI3K-AKT-WEE1 signaling pathway was identified as a key mediator of the beneficial effects of 5-MTP administration. CONCLUSION: ACE2 plays a protective role in maintaining intestinal barrier function during sepsis, potentially through modulation of the gut microbiota and the production of key metabolite 5-MTP. Our study enriched the mechanisms by which ACE2 regulates gut homeostasis and shed light on further applications. Video Abstract.