Clinical features and neurological outcomes in pediatric immune-mediated thrombotic thrombocytopenic purpura: A report from a large pediatric hematology center.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and severely reduced or absent ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) activity, with varying degrees of organ dysfunction. As TTP is rare in pediatrics, most of the medical and scientific literature has largely reported on adult patients. As a result, limited data exist regarding the clinical features, comorbidities, treatment response, and long-term outcomes in pediatric patients with immune-mediated TTP. METHODS: A single-center retrospective cohort study was conducted of all children and adolescents presenting to Children's Healthcare of Atlanta, Atlanta, Georgia, between the years 2001 and 2021 with immune-mediated TTP (iTTP). Clinical features, treatments, and outcomes, including long-term neurocognitive function, were analyzed. RESULTS: Eighteen individuals were identified, six of whom had a total of 10 relapses, amounting to 28 episodes overall. Thirty-eight percent of the patients experienced exacerbations but, ultimately, 85% achieved a clinical response and clinical remission. Only one in-hospital death occurred (mortality rate 5.5%). Seventy-three percent of analyzed patients demonstrated long-term neurocognitive abnormalities, including cognitive delay, learning difficulties, and severe depression. CONCLUSIONS: Children and adolescents recovering from iTTP are at high risk for neurocognitive deficits from initial and possibly ongoing microvascular disease. Due to risk for long-term neurological deficits, we recommend neuropsychological testing in addition to monitoring of other organ functions in all children with TTP, as well as long-term surveillance of ADAMTS13 activity during remission to detect and promptly treat early relapse.

Intramedullary Spinal Cord Tumors: Whole-Genome Sequencing to Assist Management and Prognosis.

Intramedullary spinal cord tumors (IMSCTs) harbor unique genetic mutations which may play a role in prognostication and management. To this end, we present the largest cohort of IMSCTs with genetic characterization in the literature from our multi-site institutional registry. A total of 93 IMSCT patient records were reviewed from the years 1999 to 2020. Out of these, 61 complied with all inclusion criteria, 14 of these patients had undergone genetic studies with 8 undergoing whole-genomic sequencing. Univariate analyses were used to assess any factors associated with progression-free survival (PFS) using the Cox proportional hazards model. Firth's penalized likelihood approach was used to account for the low event rates. Fisher's exact test was performed to compare whole-genome analyses and specific gene mutations with progression. PFS (months) was given as a hazard ratio. Only the absence of copy neutral loss of heterozygosity (LOH) was shown to be significant (0.05, p = 0.008). Additionally, higher risk of recurrence/progression was associated with LOH (p = 0.0179). Our results suggest LOH as a genetic predictor of shorter progression-free survival, particularly within ependymoma and glioblastoma tumor types. Further genomic research with larger multi-institutional datasets should focus on these mutations as possible prognostic factors.

Making an Impact with E.M.P.A.C.T. Engage, Mentor Prepare, Advocate, Cultivate, and Teach: An Innovative Pilot Mentoring Program Evaluation for Students Underrepresented in Medicine.

Purpose: Medicine has yet to increase the representation of historically excluded persons in medicine to reflect the general population. The lack of support and guidance in the medical training of these individuals is a significant contributor to this disparity. The Engage, Mentor, Prepare, Advocate for, Cultivate, and Teach (EMPACT) Mentoring program was created to address this problem by providing support for learners who are historically underrepresented in medicine (URiM) as they progress through medical school. Methods: The EMPACT Pilot Program was formed and conducted during the 2019-2020 academic year. A total of 19 EMPACT mentorship groups were created, each consisting of two mentors and four medical student mentees. Additionally, four professional development workshops were held along with a final Wrap-up and Awards event. Pre and post pilot program surveys along with surveys after each workshop and focus groups were conducted with a random selection of program participants. Results: When compared to data from before and after the implementation of the EMPACT program, there were statistically significant differences (p < 0.05) in EMPACT mentees reporting they agree or strongly agree they felt ready to handle their clinical rotations (28% to 65%), felt the need to have an advocate (85% to 47%), possessed insight on day-to-day activities of an attending (26% to 56%) and felt a sense of community (79% to 94%). Mentors revealed an increase in their awareness of the concepts of microaggressions and imposter phenomenon. Finally, both groups felt an increase in their support system and sense of community at the school of medicine. Conclusion: Despite COVID-19 limitations, the EMPACT program met its goals. We effectively supported URiM medical students through mentorship, networking, and community.

Permanent Cerebrospinal Fluid Diversion in Adults With Posterior Fossa Tumors: Incidence and Predictors.

BACKGROUND: Posterior fossa tumors (PFTs) can cause hydrocephalus. Hydrocephalus can persist despite resection of PFTs in a subset of patients requiring permanent cerebrospinal fluid (CSF) diversion. Characteristics of this patient subset are not well defined. OBJECTIVE: To define preoperative and postoperative variables that predict the need for postoperative CSF diversion in adult patients with PFTs. METHODS: We surveyed the CNS (Central Nervous System) Tumor Outcomes Registry at Emory (CTORE) for patients who underwent PFT resection at 3 tertiary-care centers between 2006 and 2019. Demographic, radiographic, perioperative, and dispositional data were analyzed using univariate and multivariate models. RESULTS: We included 617 patients undergoing PFT resection for intra-axial (57%) or extra-axial (43%) lesions. Gross total resection was achieved in 62% of resections. Approximately 13% of patients required permanent CSF diversion/shunting. Only 31.5% of patients who required pre- or intraop external ventricular drain (EVD) placement needed permanent CSF diversion. On logistic regression, size, transependymal flow, use of perioperative EVD, postoperative intraventricular hemorrhage (IVH), and surgical complications were predictors of permanent CSF diversion. Preoperative tumor size was only independent predictor of postoperative shunting in patients with subtotal resection. In patients with intra-axial tumors, transependymal flow (P = .014), postoperative IVH (P = .001), surgical complications (P = .013), and extent of resection (P = .03) predicted need for shunting. In extra-axial tumors, surgical complications were the major predictor (P = .022). CONCLUSION: Our study demonstrates that presence of preoperative hydrocephalus in patients with PFT does not necessarily entail the need for permanent CSF diversion. We report the major predictive factors for needing permanent CSF diversion.