Evaluating the Relationship Between Nutrition and Post-colectomy Pouchitis in Pediatric Patients with Ulcerative Colitis.

BACKGROUND: Pouchitis is the most frequent complication following restorative proctocolectomy and ileal pouch anal anastomosis (RP-IPAA) in patients with Ulcerative colitis (UC). Pediatric data on nutritional status during RP-IPAA and in patients with pouchitis are limited. AIMS: We aimed to delineate nutritional changes in children undergoing 2-stage and 3-stage surgeries and to evaluate the association between nutrition and the development of recurrent or chronic pouchitis. METHODS: This single-center retrospective study involved 46 children with UC who underwent a RP-IPAA. Data were collected at each surgical stage and for up to 2-year post-ileostomy takedown. We used Wilcoxon matched-pairs signed-rank test to evaluate the differences in nutritional markers across surgical stages and logistic regression to identify the factors associated with recurrent or chronic pouchitis. RESULTS: Twenty patients (43.5%) developed recurrent or chronic pouchitis. Children who underwent a 3-stage procedure had improvements in albumin, hematocrit, and body mass index (BMI)-for-age Z-scores (p < 0.01) between the first two stages. A positive trend in BMI-for-age Z-scores (p = 0.08) was identified in children with 2-stage procedures. All patients showed sustained nutritional improvement during the follow-up period. Among patients who underwent 3-stage surgeries, BMI worsened by 0.8 standard deviations (SDs) (p = 0.24) between the initial stages in those who developed recurrent or chronic pouchitis and improved by 1.1 SDs (p = 0.04) in those who did not. CONCLUSIONS: Early improvement in BMI-for-age Z-scores following the initial stage was associated with lower rates of recurrent or chronic pouchitis. Larger prospective studies are needed to validate these findings.

DDI-CPI, a server that predicts drug-drug interactions through implementing the chemical-protein interactome.

Drug-drug interactions (DDIs) may cause serious side-effects that draw great attention from both academia and industry. Since some DDIs are mediated by unexpected drug-human protein interactions, it is reasonable to analyze the chemical-protein interactome (CPI) profiles of the drugs to predict their DDIs. Here we introduce the DDI-CPI server, which can make real-time DDI predictions based only on molecular structure. When the user submits a molecule, the server will dock user's molecule across 611 human proteins, generating a CPI profile that can be used as a feature vector for the pre-constructed prediction model. It can suggest potential DDIs between the user's molecule and our library of 2515 drug molecules. In cross-validation and independent validation, the server achieved an AUC greater than 0.85. Additionally, by investigating the CPI profiles of predicted DDI, users can explore the PK/PD proteins that might be involved in a particular DDI. A 3D visualization of the drug-protein interaction will be provided as well. The DDI-CPI is freely accessible at http://cpi.bio-x.cn/ddi/.

Evaluating Health Literacy in Families of Injured Children: A Prospective Observational Cohort Study at a Level One Pediatric Trauma Center.

BACKGROUND: Low health literacy (HL) has been associated with poor health outcomes in children. Optimal recovery after pediatric injury requires caregiver participation in complicated rehabilitative and medical aftercare. We aimed to quantify HL among guardians of injured children and identify factors associated with low HL of guardians. METHODS: A prospective observational cohort study was conducted to evaluate the HL using the Newest Vital Sign™ of guardians of injured children (≤18 years) admitted to a level 1 pediatric trauma center. Patient and guardian characteristics were compared across levels of HL using univariate statistics. We conducted multivariable logistic regression to identify factors independently-associated with low HL. RESULTS: A sample of 95 guardian-child dyads were enrolled. The majority of guardians had low HL (n = 52, 55%), followed by moderate HL (n = 36, 38%) and high HL (n = 7, 7%). Many families received public benefits (n = 47, 49%) and 12 guardians (13%) had both housing and employment insecurity. Guardians with low HL were significantly more likely to have insecure housing and not have completed any college. CONCLUSION: The majority of injured children had a primary guardian with low HL. Pediatric trauma centers should consider screening for low HL to ensure that families have adequate post-discharge support. LEVEL OF EVIDENCE: Level 3.

Interrater reliability of chart-based assessment of functional impairment after pediatric injury using the functional status scale.

BACKGROUND: Functional impairment has been proposed as an alternative outcome for quality improvement in pediatric trauma. The functional status scale (FSS) has been used in studies of injured children, but has only been validated with resource-intensive in-person assessment. Implementation with retrospective chart-based FSS assessment would offer a simplified and scalable alternative. The purpose of this study was to evaluate interrater reliability of retrospective FSS assessment and to identify factors associated with unreliable assessment. METHODS: A retrospective cohort of admissions to a Level I pediatric trauma center between July 2020 and June 2021 was analyzed. Two physicians and two nurse registrars reviewed charts to obtain measures of six FSS domains (mental status, sensory functioning, communication, motor functioning, feeding, and respiratory status) at discharge. Functional impairment was categorized by total FSS scores as good (6,7), mild impairment (8,9), moderate impairment (10-15), severe impairment (16-21), or very severe impairment (>21). Interrater reliability was assessed using intraclass correlation (ICC). Predictors of rater disagreement were evaluated using multivariable logistic regression. RESULTS: The cohort included 443 children with a mean age of 7.4 years (standard deviation, 5.4 years) and median Injury Severity Score of 9 (interquartile range, 5-12). The median time per chart to assess FSS was 2 minutes (interquartile range, 1-2). Thirty-seven patients (8%) had functional impairment at discharge. Interrater reliability was excellent for total FSS score (ICC = 0.87) and good for FSS impairment categorization (ICC = 0.80). Rater disagreement of functional impairment categorization occurred in 14% of cases overall. Higher level of functional impairment and use of therapies (occupational and speech language therapy) were independently associated with more frequent rater disagreement. CONCLUSION: Chart-based FSS assessment is feasible and reliable, but may require more detailed review for patients with higher level of impairment that require allied health therapy. Validation of chart-based assessment is needed before widespread implementation. LEVEL OF EVIDENCE: Prognostic/Epidemiological, Level III.

Surgical management of bilateral thoracic outlet lymphaticovenous malformations causing recurrent cerebrovascular accidents.

Lymphaticovenous malformations (LVMs) are a rare subset of congenital vascular malformations that result from the defective development of the vascular and lymphatic systems during embryogenesis. LVMs can cause pathological mass effects or lead to thrombotic complications. We present a rare case of the surgical management of bilateral LVMs arising at the junction of the brachiocephalic and internal jugular veins in a patient with a patent foramen ovale, identifying the source of previously unexplained paradoxical cerebrovascular accidents.

Metabolic engineering of Escherichia coli for the biosynthesis of 2-pyrrolidone.

2-Pyrrolidone is a valuable bulk chemical with myriad applications as a solvent, polymer precursor and active pharmaceutical intermediate. A novel 2-pyrrolidone synthase, ORF27, from Streptomyces aizunensis was identified to catalyze the ring closing dehydration of γ-aminobutyrate. ORF27's tendency to aggregate was resolved by expression at low temperature and fusion to the maltose binding protein (MBP). Recombinant Escherichia coli was metabolically engineered for the production of 2-pyrrolidone from glutamate by expressing both the genes encoding GadB, a glutamate decarboxylase, and ORF27. Incorporation of a GadB mutant lacking H465 and T466, GadB_ΔHT, improved the efficiency of one-pot 2-pyrrolidone biosynthesis in vivo. When the recombinant E. coli strain expressing the E. coli GadB_ΔHT mutant and the ORF27-MBP fusion was cultured in ZYM-5052 medium containing 9 g/L of l-glutamate, 7.7 g/L of l-glutamate was converted to 1.1 g/L of 2-pyrrolidone within 31 h, achieving 25% molar yield from the consumed substrate.

Medication safety and transfusion errors in the ICU and beyond.

The modern day intensive care unit (ICU) is a place in which patients can receive continuous monitoring of physiologic variables with concentrated patient observation and care. Despite the "intensive care," errors do occur. This article reviews medication and transfusion errors, including the different types, causes, and possible solutions to prevent these errors from occurring in ICUs and the hospital at large.

Decision analysis of antibiotic and diagnostic strategies in ventilator-associated pneumonia.

The optimal strategy for ventilator-associated pneumonia remains controversial. To clarify the tradeoffs involved, we performed a decision analysis. Strategies evaluated included antibiotic therapy with and without diagnostic testing. Tests that were explored included endotracheal aspirates, bronchoscopy with protected brush or bronchoalveolar lavage, and nonbronchoscopic mini-bronchoalveolar lavage (mini-BAL). Outcomes included dollar cost, antibiotic use, survival, cost-effectiveness, antibiotic use per survivor, and the outcome perspective of financial cost-antibiotic use per survivor. Initial coverage with three antibiotics was better than expectant management or one or two antibiotic approaches, leading to both improved survival (54% vs. 66%) and decreased cost (US dollars 55447 vs. US dollars 41483 per survivor). Testing with mini-BAL did not improve survival but did decrease costs (US dollars 41483 vs. US dollars 39967) and antibiotic use (63 vs. 39 antibiotic days per survivor). From the perspective of minimizing cost, minimizing antibiotic use, and maximizing survival, the best strategy was three antibiotics with mini-BAL.