Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF) has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1) mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC

Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF) has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1) mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC

Is the timing of fixation associated with fracture-related infection among tibial plateau fracture patients with compartment syndrome? A multicenter retrospective cohort study of 729 patients.

BACKGROUND: Tibial plateau fractures with an ipsilateral compartment syndrome are a clinical challenge with limited guidance regarding the best time to perform open reduction and internal fixation (ORIF) relative to fasciotomy wound closure. This study aimed to determine if the risk of fracture-related infection (FRI) differs based on the timing of tibial plateau ORIF relative to closure of ipsilateral fasciotomy wounds. METHODS: A retrospective cohort study identified patients with tibial plateau fractures and an ipsilateral compartment syndrome treated with 4-compartment fasciotomy at 22 US trauma centers from 2009 to 2019. The primary outcome measure was FRI requiring operative debridement after ORIF. The ORIF timing relative to fasciotomy closure was categorized as ORIF before, at the same time as, or after fasciotomy closure. Bayesian hierarchical regression models with a neutral prior were used to determine the association between timing of ORIF and infection. The posterior probability of treatment benefit for ORIF was also determined for the three timings of ORIF relative to fasciotomy closure. RESULTS: Of the 729 patients who underwent ORIF of their tibial plateau fracture, 143 (19.6%) subsequently developed a FRI requiring operative treatment. Patients sustaining infections were: 21.0% of those with ORIF before (43 of 205), 15.9% at the same time as (37 of 232), and 21.6% after fasciotomy wound closure (63 of 292). ORIF at the same time as fasciotomy closure demonstrated a 91% probability of being superior to before closure (RR, 0.75; 95% CrI, 0.38 to 1.10). ORIF after fasciotomy closure had a lower likelihood (45%) of a superior outcome than before closure (RR, 1.02; 95% CrI; 0.64 to 1.39). CONCLUSION: Data from this multicenter cohort confirms previous reports of a high FRI risk in patients with a tibial plateau fracture and ipsilateral compartment syndrome. Our results suggest that ORIF at the time of fasciotomy closure has the highest probability of treatment benefit, but that infection was common with all three timings of ORIF in this difficult clinical situation

Is the timing of fixation associated with fracture-related infection among tibial plateau fracture patients with compartment syndrome? A multicenter retrospective cohort study of 729 patients.

BACKGROUND: Tibial plateau fractures with an ipsilateral compartment syndrome are a clinical challenge with limited guidance regarding the best time to perform open reduction and internal fixation (ORIF) relative to fasciotomy wound closure. This study aimed to determine if the risk of fracture-related infection (FRI) differs based on the timing of tibial plateau ORIF relative to closure of ipsilateral fasciotomy wounds. METHODS: A retrospective cohort study identified patients with tibial plateau fractures and an ipsilateral compartment syndrome treated with 4-compartment fasciotomy at 22 US trauma centers from 2009 to 2019. The primary outcome measure was FRI requiring operative debridement after ORIF. The ORIF timing relative to fasciotomy closure was categorized as ORIF before, at the same time as, or after fasciotomy closure. Bayesian hierarchical regression models with a neutral prior were used to determine the association between timing of ORIF and infection. The posterior probability of treatment benefit for ORIF was also determined for the three timings of ORIF relative to fasciotomy closure. RESULTS: Of the 729 patients who underwent ORIF of their tibial plateau fracture, 143 (19.6%) subsequently developed a FRI requiring operative treatment. Patients sustaining infections were: 21.0% of those with ORIF before (43 of 205), 15.9% at the same time as (37 of 232), and 21.6% after fasciotomy wound closure (63 of 292). ORIF at the same time as fasciotomy closure demonstrated a 91% probability of being superior to before closure (RR, 0.75; 95% CrI, 0.38 to 1.10). ORIF after fasciotomy closure had a lower likelihood (45%) of a superior outcome than before closure (RR, 1.02; 95% CrI; 0.64 to 1.39). CONCLUSION: Data from this multicenter cohort confirms previous reports of a high FRI risk in patients with a tibial plateau fracture and ipsilateral compartment syndrome. Our results suggest that ORIF at the time of fasciotomy closure has the highest probability of treatment benefit, but that infection was common with all three timings of ORIF in this difficult clinical situation