D-dimer and sinusoidal obstructive syndrome-novel poor prognostic features of thrombotic microangiopathy in children after hematopoietic cellular therapy in a single institution prospective cohort study.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a common, severe complication of allogeneic hematopoietic cellular therapy (HCT). Even when treated in many studies, morbidity and mortality rates are high. This prospective single-institution cohort study serially enrolled all allogeneic HCT recipients from August 2019-August 2022. Patients were universally screened for TA-TMA and intermediate and high-risk patients were immediately treated with eculizumab. Sub-distribution cox-proportional hazards models were used to identify sub-distribution hazard ratios (sHR)  for multi-organ dysfunction (MOD) and non-relapse-related mortality (NRM). Of 136 patients, 36 (26%) were diagnosed with TA-TMA and 21/36 (58%) developed MOD, significantly more than those without TA-TMA, (p < .0001). Of those with TA-TMA, 18 (50%) had high-risk TA-TMA (HR-TA-TMA), 11 (31%) had intermediate-risk TA-TMA (IR-TA-TMA), and 8 (22%) had standard risk (SR-TA-TMA). Twenty-six were treated with eculizumab (1/8 SR, 7/11 IR, and 18/18 HR). Elevated D-dimer predicted the development of MOD (sHR 7.6, 95% confidence interval [CI] 1.8-32.3). Children with concurrent sinusoidal obstructive syndrome (SOS) and TA-TMA had an excess risk of MOD of 34% and data supported a biologic interaction. The adjusted NRM risk was significantly higher in the TA-TMA patients (sHR 10.54, 95% CI 3.8-29.2, p < .0001), despite prompt treatment with eculizumab. Significant RF for NRM in TA-TMA patients included SOS (HR 2.89, 95% 1.07-7.80) and elevated D-dimer (HR 3.82, 95% CI 1.14-12.84). An unrelated donor source and random urine protein to creatine ratio ≥2 mg/mg were significantly associated with no response to eculizumab (odds ratio 15, 95% CI 2.0-113.6 and OR 6.5, 95% CI 1.1-38.6 respectively). TA-TMA was independently associated with NRM despite early diagnosis and treatment with eculizumab in this large pediatric transplant cohort. Prognostic implications of D-dimer in TA-TMA merit further investigation as this is a readily accessible biomarker. Concurrent SOS is an exclusion criterion of many ongoing clinical trials, but these data highlight these patients could benefit from novel therapeutic approaches. Multi-institutional clinical trials are needed to understand the impact of TA-TMA-targeted therapies.

Enhancing Curricula About Diversity, Equity, Inclusion, and Justice in Undergraduate Medical Education.

Curricula in medical education continue to evolve as societal demographics shift and medical innovation transforms the practice of medicine. The next generation of physicians must be well trained, prepared, and adept to provide health care to diverse patient populations. The last few years have witnessed increased awareness about racial and social injustice, with medical institutions acting swiftly to create and implement or enhance curricula about diversity, equity, inclusion, and justice (DEIJ) including topics such as antiracism, bias, cultural humility and sensitivity, and health care disparities and inequities. In this review article, we highlight the incorporation of DEIJ into undergraduate medical education with a focus on the standards provided by the Liaison Committee on Medical Education. We draw on examples of enacted and revised DEIJ curricula in medical education including student activism, clinical electives at pediatric residency programs targeting historically underrepresented in medicine (UIM) students, and community building for UIM students through participation in professional affinity organizations. The article also addresses current state legislation that could affect medical student learning about DEIJ and patient care. [Pediatr Ann. 2023;52(7):e249-e255.].

The Use of HPLC-PDA in Determining Nicotine and Nicotine-Related Alkaloids from E-Liquids: A Comparison of Five E-Liquid Brands Purchased Locally.

E-liquid manufacturers are under scrutiny concerning the purity and concentration accuracy of nicotine and the minor nicotine-related alkaloids (NRAs) packaged in their products. In this communication we report concentrations of nicotine and five NRAs (nornicotine, cotinine, anabasine, anatabine, myosmine) from locally purchased E-liquids. METHODS: Five brands of E-liquids (three bottles each) were purchased locally. Additionally, three bottles of reference E-liquid were prepared. Concentrations of nicotine and NRAs from each bottle were measured by HPLC. Concentrations of these alkaloids were also determined from electronic cigarette-generated aerosol and traditional cigarette smoke. RESULTS: Nicotine concentrations in E-liquid brands 1, 2, 3, 4, 5 and in the reference E-liquid were 17.8 ± 4.1, 23.2 ± 0.7, 24.0 ± 0.9, 24.9 ± 0.2, 19.7 ± 0.3 and 20.4 ± 0.1 mg/mL, respectively. Concentrations normalized to 100% of product label were 74%, 97%, 100%, 104%, 109% and 102%, respectively. E-liquid brand 1 showed significance (p < 0.001) between bottles, while the reference showed the least variability. Similar results were obtained for the NRAs. Results also indicated the NRAs in aerosol of the reference E-liquid are lower than in cigarette smoke. CONCLUSIONS: The amounts of NRAs present in E-liquids and E-liquid aerosol are less compared to cigarettes, however, inconsistencies and variation in nicotine concentrations supports the need for regulatory oversight.