Digital imaging software versus the "eyeball" method in quantifying steatosis in a liver biopsy.

Steatotic livers represent a potentially underutilized resource to increase the donor graft pool; however, 1 barrier to the increased utilization of such grafts is the heterogeneity in the definition and the measurement of macrovesicular steatosis (MaS). Digital imaging software (DIS) may better standardize definitions to study posttransplant outcomes. Using HALO, a DIS, we analyzed 63 liver biopsies, from 3 transplant centers, transplanted between 2016 and 2018, and compared macrovesicular steatosis percentage (%MaS) as estimated by transplant center, donor hospital, and DIS. We also quantified the relationship between DIS characteristics and posttransplant outcomes using log-linear regression for peak aspartate aminotransferase, peak alanine aminotransferase, and total bilirubin on postoperative day 7, as well as logistic regression for early allograft dysfunction. Transplant centers and donor hospitals overestimated %MaS compared with DIS, with better agreement at lower %MaS and less agreement for higher %MaS. No DIS analyzed liver biopsies were calculated to be >20% %MaS; however, 40% of liver biopsies read by transplant center pathologists were read to be >30%. Percent MaS read by HALO was positively associated with peak aspartate aminotransferase (regression coefficient= 1.04 1.08 1.12 , p <0.001), peak alanine aminotransferase (regression coefficient = 1.04 1.08 1.12 , p <0.001), and early allograft dysfunction (OR= 1.10 1.40 1.78 , p =0.006). There was no association between HALO %MaS and total bilirubin on postoperative day 7 (regression coefficient = 0.99 1.01 1.04 , p =0.3). DIS provides reproducible quantification of steatosis that could standardize MaS definitions and identify phenotypes associated with good clinical outcomes to increase the utilization of steatite livers.

Structural and biochemical analysis of phosphoethanolamine methyltransferase from the pine wilt nematode Bursaphelenchus xylophilus.

In free-living and parasitic nematodes, the methylation of phosphoethanolamine to phosphocholine provides a key metabolite to sustain phospholipid biosynthesis for growth and development. Because the phosphoethanolamine methyltransferases (PMT) of nematodes are essential for normal growth and development, these enzymes are potential targets of inhibitor design. The pine wilt nematode (Bursaphelenchus xylophilus) causes extensive damage to trees used for lumber and paper in Asia. As a first step toward testing BxPMT1 as a potential nematicide target, we determined the 2.05 Å resolution x-ray crystal structure of the enzyme as a dead-end complex with phosphoethanolamine and S-adenosylhomocysteine. The three-dimensional structure of BxPMT1 served as a template for site-directed mutagenesis to probe the contribution of active site residues to catalysis and phosphoethanolamine binding using steady-state kinetic analysis. Biochemical analysis of the mutants identifies key residues on the ß1d-α6 loop (W123F, M126I, and Y127F) and ß1e-α7 loop (S155A, S160A, H170A, T178V, and Y180F) that form the phosphobase binding site and suggest that Tyr127 facilitates the methylation reaction in BxPMT1.

Poor Postpartum Sleep Quality Predicts Subsequent Postpartum Depressive Symptoms in a High-Risk Sample.

STUDY OBJECTIVES: Postpartum depression (PPD) occurs in 15% to 20% of mothers worldwide and is associated with adverse outcomes for mother and child. Prior research has established a relationship between concurrent sleep quality and PPD. We conducted a secondary analysis in 45 women with mood disorders to study overall sleep quality (and individual components of sleep), measured in the early postpartum period, as a predictor of subsequent PPD. METHODS: We measured sleep quality using the Pittsburgh Sleep Quality Index (PSQI; subscale and total scores) at 1 month postpartum (and during the third trimester). We measured depressive symptoms using the Inventory of Depressive Symptoms, Self-Report (IDS-SR) at 3 months postpartum. We used bivariate and multivariate linear regression models to study the association between PSQI and IDS scores. RESULTS: We found that higher global PSQI scores as well as higher component scores for self-reported sleep quality, sleep latency, sleep efficiency, sleep medication usage, and daytime dysfunction, measured 1 month postpartum, were associated with increased IDS scores (at 3 months postpartum (P = .01, .01, .01, .003, < .001, respectively). We did not find an association between poor sleep quality in the third trimester and PPD. CONCLUSIONS: Poor sleep quality in the early postpartum period independently predicts development of later PPD. This is clinically significant and highlights the importance of sleep interventions as an immediate postpartum therapeutic tool. CITATION: McEvoy KM, Rayapati D, Washington Cole KO, Erdly C, Payne JL, Osborne LM. Poor postpartum sleep quality predicts subsequent postpartum depressive symptoms in a high-risk sample. J Clin Sleep Med. 2019;15(9):1303-1310.

Can the Ceftriaxone Breakpoints Be Increased Without Compromising Patient Outcomes?

BACKGROUND: In 2010, the Clinical Laboratory and Standards Institute recommended a 3-fold lowering of ceftriaxone breakpoints to 1 mcg/mL for Enterobacteriaceae. Supportive clinical data at the time were from fewer than 50 patients. We compared the clinical outcomes of adults with Enterobacteriaceae bloodstream infections treated with ceftriaxone compared with matched patients (with exact matching on ceftriaxone minimum inhibitory concentrations [MICs]) treated with extended-spectrum agents to determine if ceftriaxone breakpoints could be increased without negatively impacting patient outcomes. METHODS: A retrospective cohort study was conducted at 3 large academic medical centers and included patients with Enterobacteriaceae bacteremia with ceftriaxone MICs of 2 mcg/mL treated with ceftriaxone or extended-spectrum ß-lactams (ie, cefepime, piperacillin/tazobactam, meropenem, or imipenem/cilastatin) between 2008 and 2014; 1:2 nearest neighbor propensity score matching was performed to estimate the odds of recurrent bacteremia and mortality within 30 days. RESULTS: Propensity score matching yielded 108 patients in the ceftriaxone group and 216 patients in the extended-spectrum ß-lactam group, with both groups well-balanced on demographics, preexisting medical conditions, severity of illness, source of bacteremia, and source control interventions. No difference in recurrent bacteremia (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.49-2.73) or mortality (OR, 1.27; 95% CI, 0.56-2.91) between the treatment groups was observed for patients with isolates with ceftriaxone MICs of 2 mcg/mL. Only 6 isolates (1.6%) with ceftriaxone MICs of 2 mcg/mL were extended-spectrum ß-lactamase (ESBL)-producing. CONCLUSIONS: Our findings suggest that patient outcomes are similar when receiving ceftriaxone vs extended-spectrum agents for the treatment of Enterobacteriaceae bloodstream infections with ceftriaxone MICs of 2 mcg/mL. This warrants consideration of adjusting the ceftriaxone susceptibility breakpoint from 1 to 2 mcg/mL, as a relatively small increase in the antibiotic breakpoint could have the potential to limit the use of large numbers of extended-spectrum antibiotic agents.