The dynamic impact of location and resection on the glioma CSF proteome.

While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14). Using aptamer-based proteomics, we identify significant differences in the CSF proteome between lumbar, subarachnoid, and ventricular CSF. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome. Proteomic data are provided with individual clinical annotations as a resource for the field. One Sentence Summary: Glioma cerebrospinal fluid (CSF) accessed intra-operatively and longitudinally via devices can reveal impacts of treatment and anatomical location.

Expanding the phenotypic and genotypic spectrum of patients with HGSNAT-related retinopathy.

BACKGROUND: Variants in HGSNAT have historically been associated with syndromic mucopolysaccharidosis type IIIC (MPSIIIC) but more recent studies demonstrate cases of HGSNAT-related non-syndromic retinitis pigmentosa. We describe and expand the genotypic and phenotypic spectrum of this disease. MATERIALS AND METHODS: This is a retrospective, observational, case series of 11 patients with pericentral retinitis pigmentosa due to variants in HGSNAT gene without a syndromic diagnosis of MPSIIIC. We reviewed ophthalmologic data extracted from medical records, genetic testing, color fundus photos, fundus autofluorescence (FAF), and optical coherence tomography (OCT). RESULTS: Of the 11 patients, the mean age was 52 years (range: 26-78). The mean age of ophthalmologic symptoms onset was 45 years (range: 15-72). The visual acuity varied from 20/20 to 20/80 (mean 20/30 median 20/20). We described five novel variants in HGSNAT: c.715del (p.Arg239Alafs *37), c.118 G>A (p.Asp40Asn), c.1218_1220delinsTAT, c.1297A>G (p.Asn433Asp), and c.1726 G>T (p.Gly576*). CONCLUSIONS: HGSNAT has high phenotypic heterogeneity. Data from our cohort showed that all patients who had at least one variant of c.1843 G>A (p.Ala615Thr) presented with the onset of ocular symptoms after the fourth decade of life. The two patients with onset of ocular symptoms before the fourth decade did not carry this variant. This may suggest that c.1843 G>A variant is associated with a later onset of retinopathy.

The genetic counselor workforce in inherited retinal disease clinics: a descriptive assessment.

BACKGROUND: Genetic counselors (GCs) have practiced in Inherited Retinal Disease (IRD) clinics for several decades. In this small subspecialty of genetic counseling, GCs are critical for patient understanding of genetic information, which can have prognostic, systemic, family planning and therapeutic implications. Recently, both access to genetic testing for IRDs and the number of genes associated with IRDs (>350) has increased dramatically. However, the practice models and roles of IRD GCs have not been previously described. MATERIALS AND METHODS: GCs working in academic IRD clinics were surveyed to assess their experience, clinical practices, and roles performed. The collected data was compared to the broader genetic counseling profession and to other specialties using publicly available data on GC professional practices. RESULTS: While roles of IRD GCs were overlapping with those of the overall genetic counseling profession, all survey respondents reported diverse roles that included both clinical and non-clinical duties, spending up to half their time on research and educational responsibilities. Most respondents (89%) felt that their clinic's MD to GC ratio was too high, while clinical load varied. IRD GCs report varying degrees of prior genetic counseling and ophthalmology-specific experience but unanimously desire additional subspecialty-specific training. CONCLUSIONS: This descriptive assessment of a small subspecialty suggests a need for growth in the number of GCs practicing in IRD clinics and could help to inform development of new GC positions in IRD centers. It also highlights the desire for additional GC-specific education and may be relevant to curriculum development within GC programs.

Cerebrospinal fluid 2-hydroxyglutarate (2-HG) as a monitoring biomarker for IDH-mutant gliomas.

D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas 1,2 , no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs. D-2-HG and D/L-2-HG consistently decreased following tumor resection and throughout chemoradiation in patients monitored longitudinally. Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas.

"Hot Topics in Practice" Webinars: Best Practices for Public Health Webinar Development.

CONTEXT: Online education is well researched in some professions; yet, little evidence exists regarding related quality standards for public health practice-particularly with regard to popular webinar offerings. Our objective was to identify and disseminate best practices in public health webinar development for use in development of high-quality, timely webinars for public health practice. PROGRAM: We assessed data from the Hot Topics in Practice monthly webinar series that included public health professionals primarily from US Northwest states as regular webinar participants. IMPLEMENTATION: We conducted a secondary analysis, using participant evaluation data from 9 years of online questionnaires. Subsequent recommendations were developed using participants' responses to postwebinar questionnaires. Thematic analysis of qualitative quarterly reports, as well as 12 years of webinar production team knowledge, supplemented development of best practice recommendations that were not recognized through secondary analysis of respondent questionnaires alone. EVALUATION: Participant responses tended to be positive when specific practices were followed. These best practices were identified as follows: Address timely topics on current events; Feature only 1 to 2 speakers; Use a limited number of consistently formatted slides; Stay on schedule and make time for audience questions; Minimize technical difficulties; Use effective storytelling to share lessons and key data; Intentionally foster audience engagement (eg, through audience polling, question and answer); Develop clear learning objectives; Provide appropriate resources for continued learning; and Consider audience feedback for continuous improvements. DISCUSSION: Our team identified essential elements for creating high-quality, engaging webinars for public health learning. Best practice recommendations resulting from this study address gaps in quality standards and provide knowledge needed for making effective learning accessible to public health practice and supportive of advancing the field. Findings were synthesized into a practice guide, And We're Live: Creating Engaging Public Health Webinars , to aid public health learning.

Correction of Severe Coagulopathy and Hyperfibrinolysis by Tranexamic Acid and Recombinant Factor VIIa in a Cirrhotic Patient After Trauma: A Case Report.

Coagulopathy induced by trauma or cirrhosis is a well-recognized entity. Viscoelastic testing has been used in either condition for goal-directed transfusion and detection of fibrinolysis since conventional coagulation tests do not correlate with clinical risk of bleeding. Hemostatic resuscitation may not be adequate for a trauma patient with liver disease due to complex alterations in coagulation systems and occasionally require adjuvant therapy. We report a case of trauma-induced coagulopathy presenting as severe hyperfibrinolysis in a cirrhotic patient who was refractory to hemostatic resuscitation but was rapidly corrected by the administration of tranexamic acid and recombinant Factor VIIa.

Faculty teaching time: a comparison of web-based and face-to-face graduate nursing courses.

Web-based education brings a new dimension to the issue of measuring faculty workload. Current literature reflects instructor concerns related to the time required to teach web-based courses (McAlpine, Lockerbie, Ramsay & Beaman 2002; Sellani & Harrington, 2002; Smith, Ferguson & Caris, 2001). This descriptive, comparative study seeks to determine the time required to teach web-based graduate nursing courses and compare that to teaching similar courses in the face-to-face setting. Utilizing time records previously collected as part of a federally funded grant, data from 11 web-based and five face-to-face graduate level nursing courses were analyzed. Although a statistically significant difference in teaching time requirements was not demonstrated, several interesting trends did appear. Examples include differences related to preparation time and the division of teacher time while teaching web-based as opposed to face-to-face courses. Future research and continued data collection related to faculty workload and time usage will be needed as web-based courses become a growing part of graduate nursing education.