Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models. In this study, we unify these previous findings by demonstrating that TREM2 deficiency ameliorates amyloid pathology early, but exacerbates it late in disease progression in the APPPS1-21 mouse model of AD. We also demonstrate that TREM2 deficiency decreases plaque-associated myeloid cell accumulation by reducing cell proliferation, specifically late in pathology. In addition, TREM2 deficiency reduces myeloid cell internalization of amyloid throughout pathology, but decreases inflammation-related gene transcript levels selectively late in disease progression. Together, these results suggest that TREM2 plays distinct functional roles at different stages in AD pathology.

Neuroinflammation is an important contributor to Alzheimer's disease (AD) pathogenesis, as underscored by the recent identification of immune-related genetic risk factors for AD, including coding variants in the gene TREM2 (triggering receptor expressed on myeloid cells 2). Understanding TREM2 function promises to provide important insights into how neuroinflammation contributes to AD pathology. However, studies so far have produced seemingly conflicting results, with reports that amyloid pathology can be both decreased and increased in TREM2-deficient AD mouse models. In this study, we unify these previous findings by demonstrating that TREM2 deficiency ameliorates amyloid pathology early, but exacerbates it late in disease progression in the APPPS1-21 mouse model of AD. We also demonstrate that TREM2 deficiency decreases plaque-associated myeloid cell accumulation by reducing cell proliferation, specifically late in pathology. In addition, TREM2 deficiency reduces myeloid cell internalization of amyloid throughout pathology, but decreases inflammation-related gene transcript levels selectively late in disease progression. Together, these results suggest that TREM2 plays distinct functional roles at different stages in AD pathology.

OBJECTIVE: To implement a quality-improvement intervention aimed at reducing unnecessary opioid prescriptions for patients who are undergoing gynecologic surgery. METHODS: This was a retrospective cohort study that included data from the pre– and post–quality-improvement initiative cohorts. Patients at an urban, tertiary academic medical center who were undergoing scheduled minimally invasive surgery and open abdominal surgery by a gynecologic oncologist were included. Patients underwent preoperative counseling, standardization of perioperative analgesia, and a postoperative opioid prescribing algorithm. Descriptive statistics were calculated for demographic and perioperative characteristics, process measures, and outcome measures. RESULTS: A total of 532 abdominal surgeries were analyzed. The total percentage of patients discharged with an opioid prescription decreased from 82.7% (n=229/276) to 23.1% (n=59/256) (P<.001) and was significantly reduced for all routes of surgery. The mean number of opioid tablets prescribed for all patients was significantly reduced from 7.2 tablets (SD=5.7) to 1.8 tablets (SD=4.3) (P<.001). Eighty-three percent of patients (n=97/117) who underwent minimally invasive hysterectomy and were discharged on postoperative day 0 or day 1 were not provided an opioid prescription. Fifty-one percent of patients who underwent laparotomy were discharged without an opioid prescription. The percentage of patients who required an opioid refill or new prescription in the preintervention and postintervention cohorts remained constant (6.5%, n=18/276 vs 5.9%, n=15/256, P=.75), as did postoperative calls for pain (8.3%, n=23/276 vs 10.9%, n=33/256). CONCLUSION: Patients who are undergoing scheduled abdominal gynecologic surgery can be safely discharged without opioid prescriptions with appropriate education and perioperative analgesia prescribing practices. These protocols and prescribing practices profoundly limit opioid prescriptions, which is an important factor in combating the ongoing opioid crisis.

INTRODUCTION:Activity restriction (AR) is commonly recommended to pregnant patients despite lack of evidence demonstrating benefit to this practice. We describe AR recommendation patterns and identify factors associated with a higher likelihood of recommendation for AR.METHODS:This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) prospective cohort. Data were collected on nulliparous singletons at eight sites from September 2010 to September 2013. Patients were surveyed about AR recommendations at 22 weeks 0 days–29 weeks 6 days and delivery. We excluded patients missing data on AR and age. Patients were grouped by history of AR in pregnancy. We assessed characteristics between groups using χ2 and Wilcoxon rank sum tests. Associations between AR and demographic and clinical factors were examined with univariable and multivariable logistic regression.RESULTS:Of 9,312 women, 1,386 (14.9%) were recommended AR. In unadjusted analysis, prevalence of race and ethnicity, obesity, chronic hypertension, renal disease, and short cervix were significantly different between groups. After adjustment for covariates, Black and Hispanic patients were less likely to be placed on AR when compared to White patients (adjusted odds ratio [aOR] 0.81 [95% CI 0.68–0.98], and aOR 0.73 [95% CI 0.61–0.87], respectively).CONCLUSION:Activity restriction was more likely to be recommended in patients with obesity, chronic medical conditions, and short cervix. After adjustment for baseline differences, Black and Hispanic patients were significantly less likely to be recommended AR compared to White patients. While AR is not an evidence-based practice, these findings suggest implicit bias may affect which patients receive advice to limit activity in pregnancy.

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