Trends in the severity of opioid use disorder during pregnancy over time.

OBJECTIVE: Characterize severity of opioid use disorder during pregnancy over time. STUDY DESIGN: A retrospective chart review of pregnant women presenting to MetroHealth's Mother and Child Dependency program from 2002-2019 was performed. Severity of opioid use disorder was assessed by multinomial multivariable logistic regression of five discrete measures. Term birth rates and MAT use were analyzed using univariate regression. RESULTS: 606 women were included in this study. Duration of use, age at first use, polysubstance use, and route of administration did not significantly change over time. Significantly more women reported high use (>1 g daily) over time compared to low use (<0.5 g daily) (RRR = 1.21, p < 0.01). Buprenorphine use increased compared to methadone use (RRR = 1.54, p < 0.001). Rate of full-term delivery increased (RRR = 1.14, p < 0.001). CONCLUSIONS: Severity of opioid use disorder during pregnancy did not change over time. An increase in term births and preference for buprenorphine were observed.

Utility of preoperative laboratory evaluation in low-risk patients undergoing hysterectomy for benign indications.

OBJECTIVE: To evaluate whether preoperative laboratory tests are predictive of surgical complications in the first 30 days after benign hysterectomy. STUDY DESIGN: Data was collected from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) of patients undergoing benign hysterectomy between 2014 and 2016. Patients with significant medical comorbidities were excluded except for current smoking and hypertension. Patients were stratified into those who did and did not undergo preoperative testing. Laboratory results were stratified into normal and abnormal values. The primary outcome was the composite complication rate between groups. Student'st-test, Fisher's exact test, and Wilcoxon Rank-Sum were used for statistical analysis where appropriate. Multivariable regression analysis was used to determine which variables were independently predictive of postoperative complications. RESULTS: A total of 24,752 patients met all inclusion criteria. Of these, 92.5% had at least one preoperative test performed, and out of those 33.5% had an abnormal value. The most common test performed was a complete blood count, 92.5%, and the least common were coagulation studies, 16.1%. Patients who underwent testing were younger (45.9 vs 47.8 years, p < 0.001), more likely to smoke (15.3% vs 12.7%, p = 0.004) and less likely to have hypertension (18.9% vs 21.8%, p = 0.001). The most common abnormality was a low hematocrit, and the least common anomaly was an elevated international normalized ratio. The total complication rate was 9.2%, and there were no differences between groups (p = 0.07). The only lab value associated with an increased risk of complications was a hematocrit less than 34.9% (aOR 2.74, 95%CI 2.92-3.79) and WBC count >11 thousand per microliter (aOR 2.11, 95%CI 1.53-3.09). CONCLUSION: Non-hematologic preoperative laboratory anomalies are uncommon in healthy women undergoing benign hysterectomy by any modality and furthermore non-hematologic abnormalities are not predictive of post-operative complications. On the other hand, hematologic abnormalities are fairly common and a WBC above 11 cells per uL and hematocrit below 34.9% are predictive of postoperative complications.

Monosynaptic tracing maps brain-wide afferent oligodendrocyte precursor cell connectivity.

Neurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, we identified extensive afferent synaptic inputs to OPCs residing in secondary motor cortex, corpus callosum, and primary somatosensory cortex of adult mice. These inputs primarily arise from functionally-interconnecting cortical areas and thalamic nuclei, illustrating that OPCs have strikingly comprehensive synaptic access to brain-wide projection networks. Quantification of these inputs revealed excitatory and inhibitory components that are consistent in number across brain regions and stable in barrel cortex despite whisker trimming-induced sensory deprivation.

Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas.

Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)1-5 are aggressive and universally fatal pediatric brain cancers 6 . Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies7-10, and recent results suggest benefit in central nervous system malignancies11-13. Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2. Anti-GD2 CAR T cells incorporating a 4-1BBz costimulatory domain 14 demonstrated robust antigen-dependent cytokine generation and killing of DMG cells in vitro. In five independent patient-derived H3-K27M+ DMG orthotopic xenograft models, systemic administration of GD2-targeted CAR T cells cleared engrafted tumors except for a small number of residual GD2lo glioma cells. To date, GD2-targeted CAR T cells have been well tolerated in clinical trials15-17. Although GD2-targeted CAR T cell administration was tolerated in the majority of mice bearing orthotopic xenografts, peritumoral neuroinflammation during the acute phase of antitumor activity resulted in hydrocephalus that was lethal in a fraction of animals. Given the precarious neuroanatomical location of midline gliomas, careful monitoring and aggressive neurointensive care management will be required for human translation. With a cautious multidisciplinary clinical approach, GD2-targeted CAR T cell therapy for H3-K27M+ diffuse gliomas of pons, thalamus and spinal cord could prove transformative for these lethal childhood cancers.