Children with supratentorial midline pilocytic astrocytomas exhibit multiple progressions and acquisition of neurologic deficits over time

Pilocytic astrocytomas are the most common solid tumor of childhood and can arise anywhere in the central nervous system, including the posterior fossa (pf-PA), supratentorial midline (sm-PA; including optic pathway, hypothalamus, thalamus), and brainstem (bs-PA). Location (sm, bs) has been previously proposed as a prognostic factor for PA, but is difficult to separate from resection status on multivariate analysis. To overcome this limitation, we assembled a large cohort of children (n = 251) with biopsy-proved PA treated at St. Louis Children’s Hospital from 2003 – 2021 and analyzed outcomes only in patients with subtotal resection (STR; n = 81). We excluded patients with NF1, as NF1-associated gliomas often display a more indolent clinical course than their counterparts. We identified that children with STR sm-PA had a higher likelihood of multiple progressions compared to children with STR bs-PA and pf-PA. This was associated with worsening neurologic deficits over time, consistent with the sm location as a poor prognostic factor. Furthermore, the only children in our cohort with leptomeningeal dissemination or death harbored sm-PAs. Tumors in this location were also associated with an increased likelihood of non-BRAF-fusion genetic alterations and multiple oncogenic mutations. Overall, these data support location as an independent prognostic factor for PA in cases in which a gross-total resection cannot be achieved. Treating neuro-oncologists may thus wish to consider early intervention rather than watch-and-wait strategies at first progression of STR sm-PA. These patients may also benefit from earlier consideration of molecularly targeted therapy

An assessment of pediatric residency applicant perceptions of Fit during the virtual interview era

PURPOSE: Residency recruitment events and interviews are widely considered an integral component of the residency match experience. Due to the COVID-19 pandemic, residency recruitment and interviewing throughout the 2020-2021 academic year were performed virtually, which created challenges for applicants\u27 ability to discern fit to a program. Given this change, it is reasonable to suspect that applicants would be less able to discern program fit. Therefore, this study evaluated how virtual interviews impacted pediatric residency applicants\u27 ability to assess factors contributing to fit and subsequently how applicants assessed their self-perceived fit to their top-ranked programs. METHODS: An online, anonymous survey was distributed to all residency applicants who applied to any specialty at our large academic institution. The survey utilized a 5-point Likert-type scale to evaluate qualities of fit as well as the applicants\u27 self-perceived ability to assess these qualities through a virtual platform. RESULTS: 1,840 surveys were distributed, of which 473 residency applicants responded (25.7% response rate). Among these responses, 81 were pediatric applicants (27.6%). Factors deemed most important in determining fit included how well the residents get along with one another (98.8%), how much the program appeared to care about its trainees (97.5%), and how satisfied residents were with their program (97.5%). Qualities deemed most difficult for applicants to discern included the quality of facilities (18.6%), patient diversity (29.4%), and how well the residents got along with one another (30.2%). When compared to all other residency applicants, pediatric applicants placed more value on whether a program was family-friendly (p = 0.015), the quality of the facilities (p = 0.009), and the on-call system (p = 0.038). CONCLUSION: This study highlights factors that influence pediatric applicants\u27 perception of fit into a program. Unfortunately, many factors deemed most important for pediatric applicants were also among the most difficult to assess virtually. These include resident camaraderie, whether a program cares about its residents, and overall resident satisfaction. Taken together, these findings and the recommendations presented should be considered by all residency program leaders to ensure the successful recruitment of a pediatric residency class

Hormonal responses to cholinergic input are different in humans with and without type 2 diabetes mellitus

<div><p>Peripheral muscarinic acetylcholine receptors regulate insulin and glucagon release in rodents but their importance for similar roles in humans is unclear. Bethanechol, an acetylcholine analogue that does not cross the blood-brain barrier, was used to examine the role of peripheral muscarinic signaling on glucose homeostasis in humans with normal glucose tolerance (NGT; n = 10), impaired glucose tolerance (IGT; n = 11), and type 2 diabetes mellitus (T2DM; n = 9). Subjects received four liquid meal tolerance tests, each with a different dose of oral bethanechol (0, 50, 100, or 150 mg) given 60 min before a meal containing acetaminophen. Plasma pancreatic polypeptide (PP), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucose, glucagon, C-peptide, and acetaminophen concentrations were measured. Insulin secretion rates (ISRs) were calculated from C-peptide levels. Acetaminophen and PP concentrations were surrogate markers for gastric emptying and cholinergic input to islets. The 150 mg dose of bethanechol increased the PP response 2-fold only in the IGT group, amplified GLP-1 release in the IGT and T2DM groups, and augmented the GIP response only in the NGT group. However, bethanechol did not alter ISRs or plasma glucose, glucagon, or acetaminophen concentrations in any group. Prior studies showed infusion of xenin-25, an intestinal peptide, delays gastric emptying and reduces GLP-1 release but not ISRs when normalized to plasma glucose levels. Analysis of archived plasma samples from this study showed xenin-25 amplified postprandial PP responses ~4-fold in subjects with NGT, IGT, and T2DM. Thus, increasing postprandial cholinergic input to islets augments insulin secretion in mice but not humans.</p><p><b><i>Trial Registration</i>:</b> ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01434901?term=NCT01434901&rank=1" target="_blank">NCT01434901</a></p></div

The Effects of Business Failure Experience on Successive Entrepreneurial Engagements: An Evolutionary Phase Model

This study draws insights from the literatures on entrepreneurial learning from failure and organizational imprinting to develop an evolutionary phase model to explain how prior business failure experience influences successive newly started businesses. Using multiple case studies of entrepreneurs located in an institutionally developing society in Sub-Sahara Africa, we uncover four distinctive phases of post-entrepreneurial business failure: grief and despair, transition, formation and legacy phases. We find that while the grieving and transition phases entailed processes of reflecting and learning lessons from the business failure experiences, the formation and legacy phases involve processes of imprinting entrepreneurs’ experiential knowledge on their successive new start-up firms. We conclude by outlining a number of fruitful avenues for future research

2,4-Dinitrophenol, the inferno drug: a netnographic study of user experiences in the quest for leanness.

Background: Despite not being licensed for human consumption, the Internet has triggered renewed, widespread interest and availability of 2,4-Dinitrophenol (DNP). DNP, a cellular metabolic poison, causes thermogenesis resulting in fat burning and weight loss. Whilst extensively available for purchase online, research on user experiences of DNP is limited. Methods: A netnographic approach was used to describe user experiences of DNP via online public websites. Public websites discussing DNP were identified and a purposeful sample selected. Discussion threads were downloaded and a textual qualitative analysis conducted. Four themes containing 71 categories were generated. Results: There exists a plethora of communal folk pharmacological advice and recommendations for DNP manufacture and use, together with associated harms and outcomes. The efficacy and untoward effects of DNP were described and discussed alongside the notion that DNP should only be used by experienced bodybuilders. Dosage and regimes for optimal use were also described. Conclusion: This unique study provides a rich examination of the knowledge, attitudes, and motivations of DNP users, illustrating the significant role of online public websites in sharing information. Further understanding of DNP users and the online communities in which they reside is warranted to facilitate engagement and formulate appropriate and effective policy responses

Context-Responsive Anticoagulation Reduces Complications in Pediatric Extracorporeal Membrane Oxygenation

Purpose: We sought to determine the impact of a comprehensive, context-responsive anticoagulation and transfusion guideline on bleeding and thrombotic complication rates and blood product utilization during extracorporeal membrane oxygenation (ECMO).Design: Single-center, observational pre- and post-implementation cohort study.Setting: Academic pediatric hospital.Patients: Patients in the PICU, CICU, and NICU receiving ECMO support.Interventions: Program-wide implementation of a context-responsive anticoagulation and transfusion guideline.Measurements: Pre-implementation subjects consisted of all patients receiving ECMO between January 1 and December 31, 2012, and underwent retrospective chart review. Post-implementation subjects consisted of all ECMO patients between September 1, 2013, and December 31, 2014, and underwent prospective data collection. Data collection included standard demographic and admission data, ECMO technical specifications, non-ECMO therapies, coagulation parameters, and blood product administration. A novel grading scale was used to define hemorrhagic complications (major, intermediate, and minor) and major thromboembolic complications.Main Results: Seventy-six ECMO patients were identified: 31 during the pre-implementation period and 45 in the post-implementation period. The overall observed mortality was 33% with no difference between groups. Compared to pre-implementation, the post-implementation group experienced fewer major hemorrhagic and major thrombotic complications and less severe hemorrhagic complications and received less RBC transfusion volume per kg.Conclusions: Use of a context-responsive anticoagulation and transfusion guideline was associated with a reduction in hemorrhagic and thrombotic complications and reduced RBC transfusion requirements. Further evaluation of guideline content, compliance, performance, and sustainability is needed