Faculty Bibliography

BACKGROUND:The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. METHODS:In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. RESULTS:The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). CONCLUSIONS:The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

PURPOSE/UNASSIGNED:To determine the characteristics of normal tension glaucoma referrals at a tertiary care center and risk factors associated with unilateral versus bilateral disease. PATIENTS AND METHODS/UNASSIGNED:Medical records were reviewed of patients who were referred to a single glaucoma provider at a tertiary care center and were given a presumptive diagnosis of normal tension glaucoma (NTG) between the years 2018 and 2021. Data collected included demographics, medical and family history, ophthalmic history, ophthalmic examination findings, neuro-ophthalmology referrals, and magnetic resonance imaging (MRI) results. RESULTS/UNASSIGNED:A total of 98 patients were included in this study. The majority of patients (82%) had bilateral disease at initial presentation. Most patients (65%) had a history of systemic disease, including hypertension (32%), cardiovascular disease (19%), diabetes (12%), obstructive sleep apnea (10%), or orthostatic hypotension (4%). Conditions associated with vascular dysregulation were identified in 24% of patients. Sixty six percent of patients had a family history of glaucoma, while nearly half (49%) were myopic. Of patients with unilateral disease, 39% had workup or consideration of other neuro-ophthalmic diagnoses compared to 13% of patients with bilateral disease (P = 0.01). CONCLUSION/UNASSIGNED:Patients referred for NTG commonly present with disc changes in both eyes. Clinicians should assess for the presence of systemic diseases associated with vascular dysregulation, myopia, and a family history of glaucoma. Patients with unilateral disease consistent with NTG may benefit from additional workup including neuroimaging or a neuro-ophthalmic evaluation.

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.

Idursulfase is the first-line and only available enzyme replacement therapy (ERT) for Mucopolysaccharidosis type II (MPS II), or Hunter Syndrome. Deficiency in the lysosomal enzyme iduronate-2-sulfatase leads to progressive skeletal deformities, neurologic deterioration, airway obstruction, and cardiomyopathy. In severe cases, these deformities can lead to death during teenage years (Stapleton et al. 2017). Continuous treatment with ERT is essential to prevent irreversible changes. However, 16 out of 108 (15%) patients had hypersensitivity reactions to idursulfase during clinical trials. Hypersensitivity reactions have also been reported several years into treatment (Elaprase 2018). Therefore, it is critical to evaluate for hypersensitivity reactions and desensitize patients to idursulfase. We report a fourteen-year-old male who was evaluated using a nonirritating skin test concentration and underwent a novel desensitization protocol for Lysosomal Storage Disease ERT.

Neuronal activities that synchronize with the breathing rhythm have been found in humans and a host of mammalian species, not only in brain areas closely related to respiratory control or olfactory coding but also in areas linked to emotional and higher cognitive functions. In parallel, evidence is mounting for modulations of perception and action by the breathing cycle. In this Review, we discuss the extent to which brain activity locks to breathing across areas, levels of organization and brain states, and the physiological origins of this global synchrony. We describe how waves of sensory activity evoked by nasal airflow spread through brain circuits, synchronizing neuronal populations to the breathing cycle and modulating faster oscillations, cell assembly formation and cross-area communication, thereby providing a mechanistic link from breathing to neural coding, emotion and cognition. We argue that, through evolution, the breathing rhythm has come to shape network functions across species.

A 42-year-old female with a history of pemphigus vulgaris was started on rituximab after an inadequate response to corticosteroids. One month following the second cycle of rituximab, she developed acute interstitial pneumonia, which was linked to rituximab since a thorough workup revealed no evidence of an infectious cause. We initiated her on broad-spectrum intravenous (IV) antibiotics and antifungals, but the patient responded significantly to pulse methylprednisolone therapy.

Primary brain tumors are the most common solid tumor and cause of cancer-related deaths in children. Their clinical presentation depends on the age of the child and the location of tumor. Tumors in infancy often present with nonspecific symptoms, while focal neurological symptoms are more evident in older children. In this article, we review the most common acute neurological effects of pediatric primary brain tumors and their treatments.