Prevalence and risk factors associated with the need for surgical intervention due to necrotizing enterocolitis in very low birth weight infants.

INTRODUCTION: Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies affecting very low birth weight (VLBW) infants with an incidence of 6-15 %. Early recognition is crucial. Mortality is high and variable (30-50 %). Those requiring surgical intervention have a higher mortality rate than those who receive medical treatment. OBJECTIVES: 1) To assess the prevalence of surgical NEC and associated risk factors 2) To compare outcomes based on the type of treatment required 3) To estimate the mortality associated with NEC and surgical NEC. METHODS: A multicentre retrospective cohort study was designed (level II), including VLBW infants born between 2011 and 2020 in Centers of the Neocosur Network. A multivariate logistic regression analysis was performed to evaluate risk factors associated with the need for surgery. RESULTS: NEC was diagnosed in 1679 (10.4 %) of 16,131 births in this period. The prevalence of surgery was 25 % (95 % CI 23-27 %). In multivariable analysis, variables associated with an increased risk of surgery requirement were birth weight <750 g (aOR 1.73-95%CI 1.2-2.5) and receiving antenatal antibiotics (aOR 1.54-95%CI 1.09-2.74). Those requiring surgery had significantly higher morbidity and mortality than the ones receiving medical treatment. CONCLUSION: In VLBW infants with NEC, lower birth weight and antenatal antibiotics administration were independently associated with the need for surgical intervention.

Early high amino-acid intake is associated with hypophosphatemia in preterm infants.

OBJECTIVE: To estimate the incidence of hypophosphatemia in preterm infants according to parenteral nutrition received and to evaluate associated risk factors. DESIGN: A prospective multicenter cohort study included 111 patients ≤ 1250 g (7 NICUs of the NEOCOSUR Network). Two groups were compared according to the amino-acid supply in the first 48 h: aggressive parenteral group ≥ 3 g/kg/day and standard parenteral group: <2.9 g/kg/day. Hypophosphatemia was defined as serum phosphate < 4 mg/dl. A logistic regression analysis was performed to evaluate associated risk factors. RESULTS: Fifty-eight infants received aggressive parenteral nutrition. The incidence of hypophosphatemia was significantly higher in the aggressive parenteral group (77.5% vs 53.8%, p = 0.009). Hypophosphatemia was independently associated with aggressive parenteral nutrition (aOR 4.16 95% CI 1.54-12.24) and negatively associated with phosphorous intake (aOR 0.92 95% CI 0.87-0.97). CONCLUSION: Both high amino-acid intake and low phosphorus supply during the first days after birth were independently associated with hypophosphatemia.

Virulence genes of Rickettsia rickettsii are differentially modulated by either temperature upshift or blood-feeding in tick midgut and salivary glands.

BACKGROUND: Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever, is transmitted to humans by ticks. During tick feeding, R. rickettsii is exposed to both temperature elevation and components of the blood meal, which have previously been associated with the reactivation of its virulence. These environmental stimuli were also reported to modulate virulence genes of R. rickettsii infecting a set of organs of adult females of its natural vector, Amblyomma aureolatum. METHODS: In this study, we determined the effects of a temperature upshift, blood-feeding, and both stimuli simultaneously on the expression of 85 selected genes of R. rickettsii infecting either the midgut (MG) or salivary glands (SG) of male and female A. aureolatum by microfluidic high-throughput RT-qPCR. These two organs are key for acquisition of this bacterium by the tick and transmission to the vertebrate host, respectively. RESULTS: Data showed that these environmental stimuli exert distinct effects on rickettsial transcription depending on the colonized organ and gender of the vector. Temperature upshift induced the majority of differentially expressed genes of R. rickettsii in tick SG, including tRNA synthetases encoding genes. On the contrary, blood-feeding downregulated most of differentially expressed genes in both organs, but induced type IV secretion system components and OmpB in tick MG. The combined effects of both stimuli resulted in a merged gene expression profile representing features of each stimulus analyzed independently, but was more similar to the profile induced by blood-feeding. CONCLUSION: The upregulation of the majority of differentially expressed genes in tick SG by temperature upshift suggests that this stimulus is important to prepare R. rickettsii for transmission to the vertebrate host. Blood-feeding, on the other hand, induced important virulence genes in the tick MG, which might be associated with colonization of the tick and transmission to the vertebrate host. The role of the proteins identified in this study must be addressed and might help to define future targets to block tick infection, thereby preventing RMSF. To our knowledge, this is the first transcriptional tissue-specific study of a virulent strain of R. rickettsii infecting a natural tick vector.

Natural blood feeding and temperature shift modulate the global transcriptional profile of Rickettsia rickettsii infecting its tick vector.

Rickettsia rickettsii is an obligate intracellular tick-borne bacterium that causes Rocky Mountain Spotted Fever (RMSF), the most lethal spotted fever rickettsiosis. When an infected starving tick begins blood feeding from a vertebrate host, R. rickettsii is exposed to a temperature elevation and to components in the blood meal. These two environmental stimuli have been previously associated with the reactivation of rickettsial virulence in ticks, but the factors responsible for this phenotype conversion have not been completely elucidated. Using customized oligonucleotide microarrays and high-throughput microfluidic qRT-PCR, we analyzed the effects of a 10°C temperature elevation and of a blood meal on the transcriptional profile of R. rickettsii infecting the tick Amblyomma aureolatum. This is the first study of the transcriptome of a bacterium in the genus Rickettsia infecting a natural tick vector. Although both stimuli significantly increased bacterial load, blood feeding had a greater effect, modulating five-fold more genes than the temperature upshift. Certain components of the Type IV Secretion System (T4SS) were up-regulated by blood feeding. This suggests that this important bacterial transport system may be utilized to secrete effectors during the tick vector's blood meal. Blood feeding also up-regulated the expression of antioxidant enzymes, which might correspond to an attempt by R. rickettsii to protect itself against the deleterious effects of free radicals produced by fed ticks. The modulated genes identified in this study, including those encoding hypothetical proteins, require further functional analysis and may have potential as future targets for vaccine development.