Effect of accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT-A) and carrier screening for patients undergoing in vitro fertilization.

This retrospective cohort study assessed the accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT-A) and carrier screening in a single academic Reproductive Endocrinology and Infertility (REI) clinic. A total of 420 patients were evaluated with 219 patients counseled by a REI physician only and 201 patients after the addition of a genetic counselor (GC) to the REI clinic team. Cycles initiated before hiring of a GC (pre-GC) were assessed from June 2018 to December 2018 and after integration of a GC (post-GC) from March 2019 to August 2019. Additionally, information regarding carrier screening was collected if available in the medical record. Results showed more patients utilized PGT-A post-GC (9.5% vs. 5.5%), although the difference between groups did not reach statistical significance (p = 0.12). Individuals who were screened post-GC or who started screening pre-GC and continued screening post-GC were screened for a larger number of conditions than if they were only screened pre-GC (median pre-GC = 3, post-GC = 27, pre- and post-GC = 274; p < 0.0001). The change in practice from using physician-only counseling to counseling with accessibility to a GC did not change the utilization of PGT-A in a single clinic.

Etiology- and region-specific characteristics of transependymal cerebrospinal fluid flow.

OBJECTIVE: Transependymal flow (TEF) of CSF, often delineated as T2-weighted hyperintensity adjacent to the lateral ventricles on MRI, is a known imaging finding, usually in the setting of CSF flow disturbances. Specific radiological features of TEF and their relationships with clinical markers of hydrocephalus and underlying disease pathology are not known. Here, the authors describe the radiological features and clinical associations of TEF with implications for CSF circulation in the setting of intracranial pathology. METHODS: After obtaining IRB review and approval, the authors reviewed the radiological records of all patients who underwent intracranial imaging with CT or MRI at St. Louis Children's Hospital, St. Louis, Missouri, between 2008 and 2019 to identify individuals with TEF. Then, under direct review of imaging, TEF pattern, degree, and location and underlying pathology and other radiological and clinical features pertaining to CSF circulation and CSF disturbances were noted. RESULTS: TEF of CSF was identified in 219 patients and was most prevalent in the setting of neoplasms (72%). In 69% of the overall cohort, TEF was seen adjacent to the anterior aspect of the frontal horns and the posterior aspect of the occipital horns of the lateral ventricles, and nearly half of these patients also had TEF dorsal to the third ventricle near the splenium of the corpus callosum. This pattern was independently associated with posterior fossa medulloblastoma when compared with pilocytic astrocytoma (OR 4.75, 95% CI 1.43-18.53, p = 0.0157). Patients with congenital or neonatal-onset hydrocephalus accounted for 13% of patients and were more likely to have TEF circumferentially around the ventricles without the fronto-occipital distribution. Patients who ultimately required permanent CSF diversion surgery were more likely to have the circumferential TEF pattern, a smaller degree of TEF, and a lack of papilledema at the time of CSF diversion surgery. CONCLUSIONS: CSF transmigration across the ependyma is usually restricted to specific periventricular regions and is etiology specific. Certain radiological TEF characteristics are associated with tumor pathology and may reflect impaired or preserved ependymal fluid handling and global CSF circulation. These findings have implications for TEF as a disease-specific marker and in understanding CSF handling within the brain.

L-plastin enhances NLRP3 inflammasome assembly and bleomycin-induced lung fibrosis.

Macrophage adhesion and stretching have been shown to induce interleukin (IL)-1ß production, but the mechanism of this mechanotransduction remains unclear. Here we specify the molecular link between mechanical tension on tissue-resident macrophages and activation of the NLRP3 inflammasome, which governs IL-1ß production. NLRP3 activation enhances antimicrobial defense, but excessive NLRP3 activity causes inflammatory tissue damage in conditions such as pulmonary fibrosis and acute respiratory distress syndrome. We find that the actin-bundling protein L-plastin (LPL) significantly enhances NLRP3 assembly. Specifically, LPL enables apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) oligomerization during NLRP3 assembly by stabilizing ASC interactions with the kinase Pyk2, a component of cell-surface adhesive structures called podosomes. Upon treatment with exogenous NLRP3 activators, lung-resident alveolar macrophages (AMs) lacking LPL exhibit reduced caspase-1 activity, IL-1ß cleavage, and gasdermin-D processing. LPL-/- mice display resistance to bleomycin-induced lung injury and fibrosis. These findings identify the LPL-Pyk2-ASC pathway as a target for modulation in NLRP3-mediated inflammatory conditions.

Representation of female neurosurgeons as abstract authors at neurological surgery conferences.

OBJECTIVE: Female neurosurgeon representation has increased, but women still represent only 8.4% of neurosurgeons in the US. Women are significantly underrepresented as authors in neurosurgical and spine journals, a key indicator of professional success in academic medicine. In this study, the authors aimed to assess the gender diversity of first and last authors of accepted abstracts at neurosurgical conferences in 2015 and 2019. METHODS: Annual meeting abstracts for 2015 and 2019 of the American Association of Neurological Surgeons (AANS), Congress of Neurological Surgeons (CNS), and pediatrics, spine, stereotactic and functional surgery, and cerebrovascular AANS/CNS subspecialty sections were obtained and analyzed for gender. Partial data were obtained for tumor and pain sections. Composite gender data were obtained from the societies. Percentage differences were calculated using comparison of proportions testing. RESULTS: Overall, female neurosurgeons accounted for only 8.3% of first and 5.8% of last authors, and 7.2% of authors overall. The pediatrics section had the highest proportion of female neurosurgeons as first (13.7%) and last (12.4%) abstract authors, while the spine section had the lowest proportions of female neurosurgeon first (4.6%) and last (2.0%) authors. Qualitatively, a higher proportion of women were first authors, while a higher proportion of men were last authors. Overall, there was no significant change in female neurosurgeon authorship between 2015 and 2019. With regard to society demographics, female neurosurgeons accounted for only 6.3% of AANS membership. The pediatrics section had the highest proportion of female neurosurgeons at 18.1% and the stereotactic and functional surgery section had the lowest of the subspecialty sections (7.6%). While female neurosurgeons represented 12.6% of spine section membership, they represented only 4.7% of first authors (-7.9% difference; p < 0.0001) and 2.4% of last authors (-10.2% difference; p < 0.0001). For the 2019 cerebrovascular section, female neurosurgeons were underrepresented as presenting authors (5.8%) compared with their membership representation (14.8%, -9.0% difference; p = 0.0018). CONCLUSIONS: Despite an increase in the number of female neurosurgeons, there has not been a corresponding increase in the proportion of female neurosurgeons as abstract authors at annual neurosurgery conferences, and female neurosurgeons remain underrepresented as authors compared with their male colleagues.

A randomized controlled trial to evaluate the use of a web-based application to manage medications during in vitro fertilization.

OBJECTIVE: To evaluate the use of a web-based application that assists in medication management during in vitro fertilization (IVF) treatment. DESIGN: Multicenter randomized controlled trial. SETTING: University hospitals. PATIENT(S): Women undergoing IVF. INTERVENTION(S): Subjects were recruited to assess quality of life during IVF and were randomly assigned to use either the OnTrack application to assist with medication management or conventional medication management. Surveys were administered at four time points. MAIN OUTCOME MEASURE(S): Medication surplus, incidence of medication errors, amount of patient-initiated communication, and patient satisfaction. RESULT(S): A total of 153 women participated. The average number of portal messages and telephone calls was similar between groups. Twelve patients in the control group (12/69, 17.4%) and 8 patients in the case group (8/72, 11.1%) made medication errors. There were similar amounts of medication surplus in the two groups. The estimated cost of medication waste was $2,578 ± $2,056 in the control group and $2,554 ± $1,855 in the case group. Patient satisfaction was similar between the two groups. CONCLUSION(S): Use of a web-based application did not decrease medication errors, medication surplus, or patient-initiated messages. Many patients had a medication surplus, which can be an area of cost reduction during IVF. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT03383848.