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RATIONALE: Bronchopulmonary dysplasia (BPD) is the most common morbidity affecting very preterm infants. Gut fungal and bacterial microbial communities contribute to multiple lung diseases and may influence BPD pathogenesis. METHODS: We performed a prospective, observational cohort study comparing the multikingdom fecal microbiota of 144 preterm infants with or without moderate to severe BPD by sequencing the bacterial 16S and fungal ITS2 ribosomal RNA gene. To address the potential causative relationship between gut dysbiosis and BPD, we used fecal microbiota transplant in an antibiotic-pseudohumanized mouse model. Comparisons were made using RNA sequencing, confocal microscopy, lung morphometry, and oscillometry. RESULTS: We analyzed 102 fecal microbiome samples collected during the second week of life. Infants who later developed BPD showed an obvious fungal dysbiosis as compared to infants without BPD (NoBPD, p = 0.0398, permutational multivariate ANOVA). Instead of fungal communities dominated by Candida and Saccharomyces, the microbiota of infants who developed BPD were characterized by a greater diversity of rarer fungi in less interconnected community architectures. On successful colonization, the gut microbiota from infants with BPD augmented lung injury in the offspring of recipient animals. We identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. CONCLUSIONS: The gut fungal microbiome of infants who will develop BPD is dysbiotic and may contribute to disease pathogenesis.
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Patients with severe burn injuries often require split-thickness skin grafting to expedite wound healing with the thigh being a common donor site. Uncontrolled pain is associated with increased opioid consumption, longer lengths of stay, and delay in functional recovery. Peripheral nerve blocks are increasing in popularity although supportive literature is limited, and techniques vary. The purpose of this case series is to assess the safety, feasibility, and clinical efficacy of a recently demonstrated novel continuous LAM (lateral, anterior, medial) femoral cutaneous block technique in a larger cohort. The study was a dual IRB approved, observational case series from a single verified burn center. The electronic health record was retrospectively reviewed for patients admitted between June 2018 and May 2021 who had the continuous LAM block performed for donor site pain by the acute pain service team. Demographics were reported with descriptive statistics and morphine milligram equivalents (MME) were analyzed via Friedman analysis of variance. Forty-seven patients had a total of 53 blocks placed, where 2 patients received the LAM block on two separate occasions and 4 patients had bilateral LAM blocks placed. Most were African-American males, but mechanism of injury varied. Over half had a neurologic (17%) or psychiatric history (34%) outside of substance use. Almost three-quarters had a history of substance use with 17% being opioids, and a quarter had a history of polysubstance use. Median day from admission to LAM was 7 (2.5, 11.5) with a median duration of 4 (3, 5) days. Temperature and pressure sensation were reduced at the donor site. Quadricep strength remained intact, and median day until first ambulation after LAM placement was 2 (1, 3) days. Pain was adequately controlled, and there were no significant adverse events associated with the block. There was a significant reduction in MME after block placement (p < .001). Continuous peripheral nerve blocks offer an advantageous means of analgesia, while reducing potential adverse events associated with opioids or multimodal regimens. The novel LAM technique reduced sensation and pain without inhibiting early ambulation, and patients were able to fully participate in their rehabilitation.
