Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders.

Background: POLR3A pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders. Cases: We describe the range of movement disorders seen in six patients (four female, two male) with POLR3A variants [three novel (c.2214del, c.3775G>A, c.3905G>T) and six previously reported (c.760C>T, c.1771-7C>G, c.1909+22G>A, c.2005C>T, c.2422C>T, c.3337-11T>C)]. Patient 1 presented with a neonatal progeroid syndrome and developed parkinsonism, dystonia, ataxia, and spasticity. Patient 2 presented with infant-onset rapidly progressive chorea, and dystonia. Three patients (patients 3, 5, 6) presented predominantly with ataxia in combination with spasticity and dystonia. Patient 4 developed segmental dystonia during adolescence and ataxia in early adulthood. Four patients had vertical gaze impairment. The most common brain MRI abnormality was T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain. Conclusion: POLR3A-related disorders exhibit significant phenotypic pleomorphism. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.

Deep Brain Stimulation for Pediatric Dystonia: A Review of the Literature and Suggested Programming Algorithm.

Deep brain stimulation (DBS) is an established intervention for use in pediatric movement disorders, especially dystonia. Although multiple publications have provided guidelines for deep brain stimulation patient selection and programming in adults, there are no evidence-based or consensus statements published for pediatrics. The result is lack of standardized care and underutilization of this effective treatment. To this end, we assembled a focus group of 13 pediatric movement disorder specialists and 1 neurosurgeon experienced in pediatric deep brain stimulation to review recent literature and current practices and propose a standardized approach to candidate selection, implantation target site selection, and programming algorithms. For pediatric dystonia, we provide algorithms for (1) programming for initial session and follow-up sessions, and (2) troubleshooting side effects encountered during programming. We discuss common side effects, how they present, and recommendations for management. This topical review serves as a resource for movement disorders specialists interested in using deep brain stimulation for pediatric dystonia.

The Phenomenology of Tics and Tic-Like Behavior in TikTok.

BACKGROUND: Pediatricians and pediatric subspecialists worldwide have reported a marked increase in functional (conversion) disorders with tic-like behaviors during the COVID-19 pandemic. These patients often report frequent viewing of Tourette syndrome (TS) TikTok videos, suggesting disease modeling. We aimed to evaluate tic phenomenology in videos posted on TikTok. METHODS: The 100 most-viewed videos under #tourettes in TikTok were randomly assigned to two of three primary reviewers (<2 years independent practice), all pediatric neurologists specializing in movement disorders, for extraction and classification of tic phenomenology. Initial disagreements were solved by consensus. If not resolved, one of five senior reviewers (>2 years independent pediatric movement disorder practice) served as a tiebreaker. In addition, two primary and one senior reviewer rated each video on a Likert scale from 1 = "All the tics are typical of TS" to 5 = "None of the tics are typical of TS". Median scores and Spearman correlation between primary and senior reviewers were calculated. RESULTS: Six videos without tic-like behaviors were excluded. Most videos depicted coprophenomena (coprolalia: 53.2%; copropraxia: 20.2%), often with unusual characteristics. Frequently, videos demonstrated atypical phenomenology such as very strong influence by the environment (motor: 54.3%; phonic: 54.3%), aggression (19.1%), throwing objects (22.3%), self-injurious behaviors (27.7%), and long phrases (>3 words; 45.7%). Most videos portrayed atypical, nontic behaviors (median [IQR] Likert ratings: 5 [4-5]). Primary vs. senior rater scores demonstrated moderate agreement (r = 0.46; P < 0.001). CONCLUSIONS: TS symptom portrayals on highly viewed TikTok videos are predominantly not representative or typical of TS.

Surgical Outcomes in Patients With Malignant Small Bowel Obstruction: A National Cohort Study.

OBJECTIVE: The study objectives were to characterize surgical outcomes for malignant small bowel obstruction (MaSBO) as compared to other small bowel obstructions (SBO) and to develop a prediction model for postoperative mortality for MaSBO. SUMMARY BACKGROUND DATA: MaSBO is a morbid complication of advanced cancers for which the optimal management remains undefined. METHODS: Patients who underwent surgery for MaSBO or SBO were identified from the National Surgical Quality Improvement Program (2005-2017). Outcomes [30-day morbidity, unplanned readmissions, mortality, postoperative length of stay (LOS)] were compared between propensity score-matched MaSBO and SBO patients. An internally validated prediction model for mortality in MaSBO patients was developed. RESULTS: Of 46,706 patients, 1612 (3.5%) had MaSBO. Although MaSBO patients were younger than those with SBO (median 63 vs 65 years, P < 0.001), they were otherwise more clinically complex, including a higher proportion with recent weight loss (22.0% vs 4.0%, P < 0.001), severe hypoalbuminemia (18.6% vs 5.2%, P < 0.001), and cytopenias. After matching (N = 1609/group), MaSBO was associated with increased morbidity [odds ratio (OR) 1.2, P = 0.004], but not readmission (OR 1.1, P = 0.48) or LOS (incidence rate ratio 1.0, P = 0.14). The odds of mortality were significantly higher for MaSBO than SBO (OR 3.3, P < 0.001). A risk-score model predicted postoperative mortality for MaSBO with an optimism-adjusted Brier score of 0.114 and area under the curve of 0.735. Patients in the highest-risk category (11.5% of MaSBO population) had a predicted mortality rate of 39.4%. CONCLUSION: Surgery for MaSBO is associated with substantial morbidity and mortality, necessitating careful patient evaluation before operative intervention.

Altered frontal-mediated inhibition and white matter connectivity in pediatric chronic tic disorders.

Tics are unique from most movement disorders, in that they are partially suppressible. As part of the inhibitory motor network, the pre-supplementary motor area is engaged in motor control and may be involved in tic physiology. We used dual-site transcranial magnetic stimulation to assess inhibitory connectivity between right pre-supplementary motor area and left primary motor cortex, which has previously been demonstrated in healthy adults. We also used diffusion tensor imaging to investigate white matter connectivity in children with chronic tics. Twelve children with chronic tic disorder and fourteen typically developing controls underwent MRI with diffusion tensor imaging indices analysis followed by single and paired-pulse transcranial magnetic stimulation with conditioning pulse over the right pre-supplementary motor area followed by left motor cortex test pulse. Neurophysiologic and imaging data relationships to measures of tic severity and suppressibility were also evaluated in tic patients. Pre-supplementary motor area-mediated inhibition of left motor cortex was present in healthy control children but not in chronic tic disorder participants. Less inhibition correlated with worse tic suppressibility (ρ = - 0.73, p = 0.047). Imaging analysis showed increased fractional anisotropy in the right superior longitudinal fasciculus, corpus callosum, corona radiata and posterior limb of the internal capsule (p < 0.05) in tic participants, which correlated with lower self-reported tic suppressibility (ρ = - 0.70, p = 0.05). Physiologic data revealed impaired frontal-mediated motor cortex inhibition in chronic tic participants, and imaging analysis showed abnormalities in motor pathways. Collectively, the neurophysiologic and neuroanatomic data correlate with tic suppressibility, supporting the relevancy to tic pathophysiology.

Isolated limb perfusion and infusion in the treatment of melanoma and soft tissue sarcoma in the era of modern systemic therapies.

BACKGROUND AND OBJECTIVES: Isolated limb perfusion (ILP) and infusion (ILI) are treatment modalities for unresectable melanoma in-transit metastases and extremity soft tissue sarcomas (STS). We sought to characterize the national trend in their utilization in the context of novel melanoma therapies introduced in 2011. METHODS: Using the National Inpatient Sample (2005-2014), patients with a primary diagnosis of limb melanoma or STS who underwent ILP/ILI were identified by diagnosis and procedure codes. Annual percent change (APC) in ILP/ILI procedures was determined. RESULTS: From 2005 through 2014, 670 and 130 ILP/ILI procedures were performed for melanoma and STS, respectively. Mean age was 64 (SD 15) years for melanoma and 59 (SD 18) years for STS. Over time, procedures for melanoma decreased with an APC of -17 (P = .019). Comparing 2005-2010 and 2011-2014, the mean number of procedures for melanoma decreased from 91 to 32 per year (P = .007). In contrast, there was no change for STS (APC 6.5, P = .39; mean 11 and 16 per year in 2005-2010 and 2011-2014, respectively, P = .46). CONCLUSIONS: ILI/ILP utilization has decreased for melanoma, but not for STS. Whether trends for ILP and ILI differed could not be determined. ILP/ILI remains an important option to consider for regional disease control.

Qualities and Methods of Highly Effective Surgical Educators: A Grounded Theory Model.

OBJECTIVE: To identify personal qualities and teaching methods of highly effective surgical educators using a novel research design. DESIGN: In this qualitative study, surgical residents were sent an electronic survey soliciting nominations for faculty perceived as highly effective surgical educators. In-depth, semistructured interviews were conducted with surgeons receiving the most nominations. Grounded theory methodology identified themes for analysis. SETTING: General, vascular, and plastic surgery residents and faculty at the University of Pennsylvania Health System. PARTICIPANTS: A total of 77 surgical residents were surveyed. Data saturation occurred after 12 semistructured interviews with attending surgeons, corresponding to the top 15% of faculty. RESULTS: Interviewees described both personal characteristics and specific teaching approaches that facilitated successful learning. These included providing exceptional surgical education as a mission, a strong influence from past mentors and role models, a love for the profession, and a low rate of self-professed burnout. Desirable teaching methods included promoting a culture of psychological safety (the perceived ability to take interpersonal risks within one's environment), progressive autonomy, accountability of trainees, and individualized teaching for the learner. Interviewees saw education as inseparable from clinical duties, and all surgeons believed providing exceptional patient care was the foundation of effective surgical teaching. The derived themes suggested that educators prefer "cognitive-based" approaches, focusing on learning processes rather than specific outcomes. CONCLUSIONS: This study identified characteristics and educational styles of highly effective educators in a cohort of academic surgeons. This framework may inform the development of educational programs for residents and faculty in effective teaching methods.

Bicuspid and unicuspid aortic valves: Different phenotypes of the same disease? Insight from the GenTAC Registry.

BACKGROUND: Unicuspid aortic valve (UAV) is a rare disorder, often difficult to distinguish from bicuspid aortic valve (BAV). BAV and UAV share valve pathology such as the presence of a raphe, leaflet fusion, aortic stenosis, aortic regurgitation, and/or ascending aortic dilatation, but a comprehensive echocardiographic comparison of patients with UAV and BAV has not been previously performed. METHODS: We investigated UAV and BAV patients at an early stage of disease included in GenTAC, a national registry of genetically related aortic aneurysms and associated cardiac conditions. Clinical and echocardiographic data from the GenTAC Registry were compared between 17 patients with UAV and 17 matched-controls with BAV. RESULTS: Baseline characteristics including demographics, clinical findings including family history of BAV and aortic aneurysm/coarctation, and echocardiographic variables were similar between BAV and UAV patients; aortic stenosis was more common and more severe in patients with UAV. This was evidenced by higher mean and peak gradient, smaller aortic valve area, and more advanced valvular degeneration (all P < .05). There were no significant differences in aortic dimensions, with a similar pattern of enlargement of the ascending aorta. CONCLUSIONS: The similar baseline characteristics with more accelerated aortic valve degeneration and stenosis suggest that UAV represents an extreme in the spectrum of BAV syndromes. Therefore, it is reasonable to consider application of recommendations for the management of patients with BAV to those with the rarer UAV.

Procedural Skills of the Entrustable Professional Activities: Are Graduating US Medical Students Prepared to Perform Procedures in Residency?

PURPOSE: Competency-based medical education has been successfully instituted in graduate medical education through the development of Milestones. Consequently, the Association of American Medical Colleges implemented the core entrustable professional activities initiative to complement this framework in undergraduate medical education. We sought to determine its efficacy by examining the experiences and confidence of recent medical school graduates with general procedural skills (entrustable professional activities 12). METHOD: We administered an electronic survey to the MedStar Georgetown University Hospital intern class assessing their experiences with learning and evaluation as well as their confidence with procedural skills training during medical school. Simple linear regression was used to compare respondent confidence and the presence of formal evaluation in medical school. RESULTS: We received 28 complete responses, resulting in a 33% response rate, whereas most respondents indicated that basic cardiopulmonary resuscitation, bag/mask ventilation, and universal precautions were important to and evaluated by their medical school, this emphasis was not present for venipuncture, intravenous catheter placement, and arterial puncture. Mean summed scores of confidence for each skill indicated a statistically significant effect between confidence and evaluation of universal precaution skills. CONCLUSIONS: More advanced procedural skills are not considered as important for graduating medical students and are less likely to be taught and formally evaluated before graduation. Formal evaluation of some procedural skills is associated with increased confidence of the learner.

Perceptions of gender-based discrimination during surgical training and practice.

BACKGROUND: Women represent 15% of practicing general surgeons. Gender-based discrimination has been implicated as discouraging women from surgery. We sought to determine women's perceptions of gender-based discrimination in the surgical training and working environment. METHODS: Following IRB approval, we fielded a pilot survey measuring perceptions and impact of gender-based discrimination in medical school, residency training, and surgical practice. It was sent electronically to 1,065 individual members of the Association of Women Surgeons. RESULTS: We received 334 responses from medical students, residents, and practicing physicians with a response rate of 31%. Eighty-seven percent experienced gender-based discrimination in medical school, 88% in residency, and 91% in practice. Perceived sources of gender-based discrimination included superiors, physician peers, clinical support staff, and patients, with 40% emanating from women and 60% from men. CONCLUSIONS: The majority of responses indicated perceived gender-based discrimination during medical school, residency, and practice. Gender-based discrimination comes from both sexes and has a significant impact on women surgeons.

GABAergic interneuron development and function is modulated by the Tsc1 gene.

Tuberous sclerosis complex (TSC) is a genetic disease with severe neurologic and psychiatric manifestations including epilepsy, developmental delay, and autism. Despite much progress in defining abnormal signaling pathways including the contribution of increased mTORC1 signaling, specific abnormalities that underlie the severe neurologic features in TSC remain poorly understood. We hypothesized that epilepsy and autism in TSC result from abnormalities of γ-aminobutyric acidergic (GABAergic) interneurons. To test this hypothesis, we generated conditional knockout mice with selective deletion of the Tsc1 gene in GABAergic interneuron progenitor cells. These interneuron-specific Tsc1 conditional knockout (CKO) mice have impaired growth and decreased survival. Cortical and hippocampal GABAergic interneurons of CKO mice are enlarged and show increased mTORC1 signaling. Total numbers of GABAergic cells are reduced in the cortex with differential reduction of specific GABAergic subtypes. Ectopic clusters of cells with increased mTORC1 signaling are also seen suggesting impaired interneuron migration. The functional consequences of these cellular changes are evident in the decreased seizure threshold on exposure to the proconvulsant flurothyl. These findings support an important role for the Tsc1 gene during GABAergic interneuron development, function, and possibly migration.