Early exposure to antibiotics in the neonatal intensive care unit alters the taxonomic and functional infant gut microbiome.

INTRODUCTION: The infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study, we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time. MATERIALS AND METHODS: Stool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed. RESULTS: A total of 51 stool samples from 25 infants were analyzed: seven infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R2 = 0.044, p = .002) but later courses did not (R2 = 0.023, p = .114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray-Curtis distance 0.29 vs. 0.63, Wilcoxon p = .06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p < .1, folate synthesis, glycerolipid metabolism, fatty acid biosynthesis, and glycolysis). No functional changes associated with current antibiotic use were identified. In a limited sample set, we saw little evidence of fungal involvement in the overall infant microbiome. CONCLUSION: Through this study, we have further characterized the role antibiotics have in the development of the infant microbiome. Antibiotics given at birth were associated with alterations in the microbiome and had significant impact on the functional pathways involved in folate synthesis and multiple metabolic pathways. Later courses of antibiotics led to stochastic dysbiosis and a significant decrease in Escherichia coli. Further characterization of the infant mycobiome is still needed.

A Low-Cost Trainer for the Surgical Management of Postpartum Hemorrhage.

INTRODUCTION: Simulation-based training to manage surgical postpartum hemorrhage allows for improved preparation for these rarely needed life-saving procedures. Our objectives were to design a low-tech simulation model for use in training and evaluation of surgical techniques for the management of postpartum hemorrhage and to present evidence of its validity in assessment and training. METHODS: Fifty-two obstetrics and gynecology residents and 25 attending physicians from an academic hospital were video recorded while performing the O'Leary and B-Lynch techniques on the low-tech model. Performance was evaluated using a Technical Skills Checklist, for B-Lynch and O'Leary techniques, and the Reznick's Global Rating Scale. Interrater reliability was computed to assess the consistency of the ratings between 2 raters. Average scores were determined and compared between incoming residents, junior residents, senior residents, and attending physicians to show construct validity. RESULTS: For the B-Lynch, Technical Skills Checklist scores (maximum 17 points) of attendings (15.04) and senior residents (15.12) were higher than those of junior residents (5.63) and new residents (3.38). Global Rating Scale scores (maximum 25 points) on the B-Lynch reflected the same increase (22.38, 19.35 vs. 8.85, 6.75, respectively). For the O'Leary stitch, the scores of attendings, senior, junior, and incoming residents were as follows: 15.20, 13.65, 11.54, and 2.83, respectively (maximum 19 points). This supports the construct validity of the model. The model was considered realistic and useful for improving surgical skills in 71.4% of participants. CONCLUSIONS: This low-cost, easily constructed model is a useful tool for training these surgical skills.

Progestin therapy for obese women with complex atypical hyperplasia: levonorgestrel-releasing intrauterine device vs systemic therapy.

BACKGROUND: Though hysterectomy remains the standard treatment for complex atypical hyperplasia, patients who desire fertility or who are poor surgical candidates may opt for progestin therapy. However, the effectiveness of the levonorgestrel-releasing intrauterine device compared to systemic therapy in the treatment of complex atypical hyperplasia has not been well studied. OBJECTIVE: We sought to examine differences in treatment response between local progestin therapy with the levonorgestrel-releasing intrauterine device and systemic progestin therapy in women with complex atypical hyperplasia. METHODS: This single-institution retrospective study examined women with complex atypical hyperplasia who received progestin therapy between 2003 and 2018. Treatment response was assessed by histopathology on subsequent biopsies. Time-dependent analyses of complete response and progression to cancer were performed comparing the levonorgestrel-releasing intrauterine device and systemic therapy. A propensity score inverse probability of treatment weighting model was used to create a weighted cohort that differed based on treatment type but was similar with respect to other characteristics. An interaction-term analysis was performed to examine the impact of body habitus on treatment response, and an interrupted time-series analysis was employed to assess if changes in treatment patterns correlated with outcomes over time. RESULTS: A total of 245 women with complex atypical hyperplasia received progestin therapy (levonorgestrel-releasing intrauterine device n = 69 and systemic therapy n = 176). The mean age and body mass index were 36.9 years and 40.0 kg/m2, respectively. In the patient-level analysis, women who received the levonorgestrel-releasing intrauterine device had higher rates of complete response (78.7% vs 46.7%; adjusted hazard ratio, 3.32; 95% confidence interval, 2.39-4.62) and a lower likelihood of progression to cancer (4.5% vs 15.7%; adjusted hazard ratio, 0.28; 95% confidence interval, 0.11-0.73) compared to those who received systemic therapy. In particular, women with class III obesity derived a higher relative benefit from levonorgestrel-releasing intrauterine device therapy in achieving complete response compared to systemic therapy: class III obesity, adjusted hazard ratio 4.72, 95% confidence interval 2.83-7.89; class I-II obesity, adjusted hazard ratio 1.83, 95% confidence interval 1.09-3.09; and nonobese, adjusted hazard ratio 1.26, 95% confidence interval 0.40-3.95. In the cohort-level analysis, the obesity rate increased during the study period (77.8% to 88.2%, 13.4% relative increase, P = .033) and levonorgestrel-releasing intrauterine device use significantly increased after 2007 (6.3% to 82.7%, 13.2-fold increase, P < .001), both concomitant with a higher proportion of women achieving complete response (32.9% to 81.4%, 2.5-fold increase, P = .005). CONCLUSION: Our study suggests that local therapy with the levonorgestrel-releasing intrauterine device may be more effective than systemic therapy for women with complex atypical hyperplasia who opt for nonsurgical treatment, particularly in morbidly obese women. Shifts in treatment paradigm during the study period toward increased levonorgestrel-releasing intrauterine device use also led to improved complete response rates despite increasing rates of obesity.