Pediatric Primary Care Diagnoses Among Children with Intrauterine Opioid Exposure.

BACKGROUND AND OBJECTIVES: Characterizing common concerns for children with intrauterine opioid exposure (IOE) can inform tailored primary care. METHODS: Retrospective analysis of primary care data of children with IOE from birth to age two years within one multi-state pediatric health system. Well child care (WCC) and problem-based visit diagnoses were categorized, and descriptive statistics were tabulated. RESULTS: Three hundred and eighty-five (385) children with IOE had 3,622 primary care visits, of which 51.4% were WCC and 48.6% were problem-based. Most frequent visit diagnoses were upper respiratory complaints (14.8% of visits), feeding difficulties (12.2%), and perinatal viral exposure (9.8%). Although visit type (WCC vs. problem-based) varied across diagnostic category, frequent utilization of both visit types were documented for several diagnoses in infancy (e.g., fussiness/colic, feeding difficulties). CONCLUSIONS: Well child care visits for children with IOE are key opportunities for anticipatory guidance with an emphasis on problems that may contribute to acute health care utilization, particularly in early infancy.

Physician Executive Leadership Plus: An Approach to Business and Management Education for Medical Students.

INTRODUCTION: Physicians are looked upon to lead the healthcare team, a task that has grown increasingly complex and interdisciplinary, requiring a diverse extra-clinical skillset. Physician Executive Leadership (PEL) Plus is a student-run program that uniquely utilizes both didactic and real-world project-based approaches to deliver a business and management curriculum to medical students. METHODS: We developed and implemented PEL Plus during the 2018-19 and 2019-20 academic years, geared at first- and second-year medical students. We provide an overview of this combined didactic and project-based curriculum, in addition to evaluating if the program was efficacious in teaching the desired skillset. We assessed short-term knowledge acquisition using multiple-choice questions, and investigated student perceptions of their learning and the program using Likert scales and narrative feedback. We also investigated the influence of student demographics on performance, in order to assess the appropriateness of our target audience. RESULTS: 28 students completed PEL Plus over the two years (14 students/year). Average performance on multiple-choice questions showed statistically significant improvement after the majority of sessions. There were no statistically significant effects of demographics on performance in the majority of sessions. Students self-rated stronger understandings of lecture topics after each session, and analysis of narrative feedback demonstrated thematic categories centred on teaching style, new knowledge, lecture content/material, projects, networking, program structure, and generic statements. DISCUSSION: PEL Plus is an innovative and effective approach to teaching business, leadership, and management skills in undergraduate medical education. Development of similar programs at other institutions will positively impact the broader medical student community.

Granulomatosis with polyangiitis masquerading as pituitary adenoma with apoplexy.

Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a small- and medium-vessel autoimmune vasculitis. Rare presentations of GPA can manifest as ophthalmologic and endocrinological deficits with sellar enhancement on imaging. While GPA typically presents distinct in appearance from other sellar pathologies, such as pituitary adenoma, we report the case of a 41-year-old woman with GPA of the pituitary that was initially diagnosed as pituitary macroadenoma with apoplexy and treated with two surgical resections without improvement of clinical symptoms. Pathology analysis of the second resection specimen revealed an inflammatory process consistent with GPA. After the pathologic and clinical diagnosis of GPA was established, treatment with steroid and steroid-sparing immunosuppressants resulted in improvements both on imaging and symptomatically. We discuss important aspects of the diagnosis and treatment of this rare presentation of GPA.

Rapidly progressive ACTH-dependent Cushing's disease masquerading as ectopic ACTH-producing Cushing's syndrome: illustrative case.

BACKGROUND: Cushing's disease (CD) remains a challenging condition to diagnose and treat. This case study highlights the challenges of diagnosing CD when faced with discrepant clinical, biochemical, and radiological findings. OBSERVATIONS: A 62-year-old man presented with rapid evolution of symptoms, including depression, fatigue, and extreme muscle atrophy, which resulted in the patient being a wheelchair user over the course of a few months. His rapid clinical course in conjunction with hypercortisolemia in the setting of a pituitary macroadenoma involving the cavernous sinus, two large pulmonary nodules, and urine-free cortisol levels in the thousands suggested an aggressive ectopic adrenocorticotropic hormone (ACTH) source. After extensive testing ruled out CD from an ectopic source and because of the patient's abrupt clinical deterioration, the authors concluded that the source was likely an aggressive pituitary adenoma. Therefore, the authors performed an endonasal transsphenoidal approach for resection of the pituitary adenoma involving the cavernous sinus, and the patient was scheduled for radiosurgery to control tumor progression. LESSONS: Although extremely high levels of cortisol and ACTH are associated with ectopic Cushing's syndrome, they may also indicate an aggressive form of CD. Suspicion should be maintained for hypercortisolemia from a pituitary source even when faced with discrepant information that may suggest an ectopic source.

Methylprednisolone Reduces Persistent Post-ischemic Inflammation in a Rat Hypoxia-Ischemia Model of Perinatal Stroke.

In perinatal stroke, the initial injury results in a chronic inflammatory response caused by the release of proinflammatory cytokines, gliosis and microglia activation. This chronic and ongoing inflammatory response exacerbates the brain injury, often resulting in encephalopathy and cerebral palsy (CP). Using a neonatal rat model of hypoxia-ischemia (HI) at postnatal day (P)7, we demonstrated that chronic inflammation is persistent and continues into the tertiary phase of perinatal stroke and can be attenuated by the administration of methylprednisolone sodium-succinate (MPSS, 30 mg/kg), a US Food and Drug Administration (FDA) approved anti-inflammatory agent. The inflammatory response was assessed by real-time quantitative PCR and ELISA for markers of inflammation (CCL3, CCL5, IL18 and TNFα). Structural changes were evaluated by histology (LFB/H&E), while cellular changes were assessed by Iba-1, ED1, GFAP, NeuN, Olig2 and CC1 immunostaining. Functional deficits were assessed with the Cylinder test and Ladder Rung Walking test. MPSS was injected 14 days after HI insult to attenuate chronic inflammation. In neonatal conditions such as CP, P21 is a clinically relevant time-point in rodents, corresponding developmentally to a 2-year-old human. Administration of MPSS resulted in reduced structural damage (corpus callosum, cortex, hippocampus, striatum), gliosis and reactive microglia and partial restoration of the oligodendrocyte population. Furthermore, significant behavioural recovery was observed. In conclusion, we demonstrated that administration of MPSS during the tertiary phase of perinatal stroke results in attenuation of the chronic inflammatory response, leading to pathophysiological and functional recovery. This work validates the high clinical impact of MPSS to treat neonatal conditions linked to chronic inflammation.

Severe-combined immunodeficient rats can be used to generate a model of perinatal hypoxic-ischemic brain injury to facilitate studies of engrafted human neural stem cells.

Cerebral palsy (CP) encompasses a group of non-progressive brain disorders that are often acquired through perinatal hypoxic-ischemic (HI) brain injury. Injury leads to a cascade of cell death events, resulting in lifetime motor and cognitive deficits. There are currently no treatments that can repair the resulting brain damage and improve functional outcomes. To date, preclinical research using neural precursor cell (NPC) transplantation as a therapy for HI brain injury has shown promise. To translate this treatment to the clinic, it is essential that human-derived NPCs also be tested in animal models, however, a major limitation is the high risk of xenograft rejection. A solution is to transplant the cells into immune-deficient rodents, but there are currently no models of HI brain injury established in such a cohort of animals. Here, we demonstrate that a model of HI brain injury can be generated in immune-deficient Prkdc knockout (KO) rats. Long-term deficits in sensorimotor function were similar between KO and wildtype (WT) rats. Interestingly, some aspects of the injury were more severe in KO rats. Additionally, human induced pluripotent stem cell derived (hiPSC)-NPCs had higher survival at 10 weeks post-transplant in KO rats when compared to their WT counterparts. This work establishes a reliable model of neonatal HI brain injury in Prkdc KO rats that will allow for future transplantation, survival, and long-term evaluation of the safety and efficacy of hiPSC-NPCs for neonatal brain damage. This model will enable critical preclinical translational research using human NPCs.