Recent Publications by CFE Educators

Melanonychia including melanonychia striata in children poses a diagnostic dilemma. Atypical clinical features often raise the possibility of malignancy, and a nail unit biopsy may be recommended. Commensurate with atypical clinical features, the histopathology may also appear alarming. However, accumulating data illustrate that most cases of melanonychia striata are benign and suggest that an alternate approach is often warranted for pediatric patients. Herein, we review the existing data regarding pediatric melanonychia striata and offer an evidence-based approach to its evaluation and management.

A racially and ethnically diverse physician workforce is critical to meeting the needs of the United States' increasingly diverse patient population. Unfortunately, Black, Latinx, American Indian, and Alaska Native communities remain underrepresented in medicine. The disproportionate impact of the COVID-19 pandemic by race/ethnicity and increased public attention to anti-Black and anti-Asian racism have inspired a growing national discourse on addressing systemic racism. Within academic medicine, there has been a call for the fundamental incorporation of antiracism into medical training and professional competency. From the perspective of a group primarily led by residents who are women of color, we describe our 6 years of experience leading a Diversity Committee that catalyzed sustained and systemic efforts to advance diversity, equity, inclusion (DEI), and antiracism at a large urban pediatrics residency program. We outline the implementation and key outcomes of the Diversity Committee's ongoing initiatives to increase resident diversity, foster an inclusive learning environment, develop a resident curriculum on DEI and antiracism, and center the needs and wisdom of the communities that our institution serves. Finally, we highlight challenges and lessons learned to inform other institutions striving to advance DEI and antiracism in academic medicine.

OBJECTIVES

Patients with metaiodobenzylguanidine (MIBG)-avid relapsed or refractory neuroblastoma after initial therapy may exhibit transient responses to salvage treatment with iodine-131 metaiodobenzylguanidine ( I-MIBG). It is unclear whether disease progression following I-MIBG treatment occurs in previously involved versus new anatomic sites of disease. Understanding this pattern of relapse will inform the use of consolidation therapy following I-MIBG administration.

METHODS

Patients with relapsed or refractory metastatic MIBG-avid neuroblastoma or ganglioneuroblastoma, who received single-agent I-MIBG, had stable or responding disease 6-8 weeks following I-MIBG, but subsequently experienced disease progression were included. MIBG scans were reviewed to establish anatomic and temporal evolution of MIBG-avid disease.

RESULTS

A total of 84 MIBG-avid metastatic sites were identified immediately prior to MIBG therapy in a cohort of 12 patients. At first progression, a total of 101 MIBG-avid sites were identified, of which 69 (68%) overlapped with pre-treatment disease sites, while 32 (32%) represented anatomically new disease areas. Eight of 12 patients had one or more new MIBG-avid sites at first progression. Of the 69 involved sites at progression that overlapped with pre-treatment disease, 11 represented relapsed sites that had cleared following MIBG therapy, two were persistent but increasingly MIBG-avid, and 56 were stably persistent.

CONCLUSIONS

Previously involved anatomic disease sites predominate at disease progression following I-MIBG treatment. Nevertheless, the majority of patients progressed in at least one new anatomic disease site. This suggests that consolidation focal therapies targeting residual disease sites may be of limited benefit in preventing systemic disease progression following I-MIBG treatment of relapsed or refractory neuroblastoma.

Peripheral nerve injury-induced neuropathic pain is a chronic and debilitating condition characterized by mechanical hypersensitivity. We previously identified microglial activation via release of colony-stimulating factor 1 (CSF1) from injured sensory neurons as a mechanism contributing to nerve injury-induced pain. Here, we show that intrathecal administration of CSF1, even in the absence of injury, is sufficient to induce pain behavior, but only in male mice. Transcriptional profiling and morphologic analyses after intrathecal CSF1 showed robust immune activation in male but not female microglia. CSF1 also induced marked expansion of lymphocytes within the spinal cord meninges, with preferential expansion of regulatory T-cells (Tregs) in female mice. Consistent with the hypothesis that Tregs actively suppress microglial activation in females, Treg deficient () female mice showed increased CSF1-induced microglial activation and pain hypersensitivity equivalent to males. We conclude that sexual dimorphism in the contribution of microglia to pain results from Treg-mediated suppression of microglial activation and pain hypersensitivity in female mice.

ALSUntangled reviews alternative and off label treatments with a goal of helping patients make more informed decisions about them. Here we review ketogenic diets. We shows that these have plausible mechanisms, including augmenting cellular energy balance and reducing excitotoxicity, neuroinflammation and oxidative stress. We review a mouse model study, anecdotal reports and trials in ALS and other diseases. We conclude that there is yet not enough data to recommend ketogenic diets for patients with ALS, especially in light of the many side effects these can have.