Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

hglobal-Index: A Novel Author-Level Measure of the Diffusion of Scientific Ideas Among High-, Low-, and Middle-Income Countries.

OBJECTIVE: To describe an intuitive and useful method for measuring the global impact of a medical scholar's research ideas by examining cross-border citations (CBCs) of peer-reviewed neurosurgical publications. METHODS: Publication and citation data for a random sample of the top 50 most academically productive neurosurgeons were obtained from Scopus Application Programming Interface. We characterized an author-level global impact index analogous to the widely used h-index, the hglobal-index, defined as the number of published peer-reviewed manuscripts with at least the same number of CBCs. To uncover socioeconomic insights, we explored the hglobal-index for high-, middle-, and low-income countries. RESULTS: The median (interquartile range) number of publications and CBCs were 144 (62-255) and 2704 (959-5325), respectively. The median (interquartile range) h-index and hglobal-index were 42 (23-61) and 32 (17-38), respectively. Compared with neurosurgeons in the random sample, the 3 global neurosurgeons had the highest hglobal-indices in low-income countries at 17, 13, and 9, despite below-average h-index scores of 33, 38, and 19, respectively. CONCLUSION: This intuitive update to the h-index uses CBCs to measure the global impact of scientific research. The hglobal-index may provide insight into global diffusion of medical ideas, which can be used for social science research, author self-assessment, and academic promotion.

Improving heart rate monitoring in the obese with time-of-flight photoplethysmography (TOF-PPG): a quantitative analysis of source-detector-distance effect.

Commercial photoplethysmography (PPG) sensors rely on the measurement of continuous-wave diffuse reflection signals (CW-DRS) to monitor heart rate. Using Monte Carlo modeling of light propagation in skin, we quantitatively evaluate the dependence of continuous-wave photoplethysmography (CW-PPG) in commercial wearables on source-detector distance (SDD). Specifically, when SDD increases from 0.5 mm to 3.3 mm, CW-PPG signal increases by roughly 846% for non-obese (NOB) skin and roughly 683% for morbidly obese (MOB) skin. Ultimately, we introduce the concept of time-of-flight PPG (TOF-PPG) which can significantly improve heart rate signals. Our model shows that the optimized TOF-PPG improves heart rate monitoring experiences by roughly 47.9% in NOB and 93.2% in MOB when SDD = 3.3 mm is at green light. Moving forward, these results will provide a valuable source for hypothesis generation in the scientific community to improve heart rate monitoring.

A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis.

No comprehensive classification system that guides prognosis and therapy of pituitary adenomas exists. The 2022 WHO histopathology-based classification system can only be applied to lesions that are resected, which represent few clinically significant pituitary adenomas. Many factors independent of histopathology provide mechanistic insight into causation and influence prognosis and treatment of pituitary adenomas. We propose a new approach to guide prognosis and therapy of pituitary adenomas by integrating clinical, genetic, biochemical, radiological, pathological, and molecular information for all adenomas arising from anterior pituitary cell lineages. The system uses an evidence-based scoring of risk factors to yield a cumulative score that reflects disease severity and can be used at the bedside to guide pituitary adenoma management. Once validated in prospective studies, this simple manageable classification system could provide a standardised platform for assessing disease severity, prognosis, and effects of therapy on pituitary adenomas.

The RAPID Consortium: A Platform for Clinical and Translational Pituitary Tumor Research.

Objectives Pituitary tumor treatment is hampered by the relative rarity of the disease, absence of a multicenter collaborative platform, and limited translational-clinical research partnerships. Prior studies offer limited insight into the formation of a multicenter consortium. Design The authors describe the establishment of a multicenter research initiative, Registry of Adenomas of the Pituitary and Related Disorders (RAPID), to encourage quality improvement and research, promote scholarship, and apply innovative solutions in outcomes research. Methods The challenges encountered during the formation of other research registries were reviewed with those lessons applied to the development of RAPID. Setting/Participants RAPID was formed by 11 academic U.S. pituitary centers. Results A Steering Committee, bylaws, data coordination center, and leadership team have been established. Clinical modules with standardized data fields for nonfunctioning adenoma, prolactinoma, acromegaly, Cushing's disease, craniopharyngioma, and Rathke's cleft cyst were created using a Health Insurance Portability and Accountability Act-compliant cloud-based platform. Currently, RAPID has received institutional review board approval at all centers, compiled retrospective data and agreements from most centers, and begun prospective data collection at one site. Existing institutional databases are being mapped to one central repository. Conclusion The RAPID consortium has laid the foundation for a multicenter collaboration to facilitate pituitary tumor and surgical research. We sought to share our experiences so that other groups also contemplating this approach may benefit. Future studies may include outcomes benchmarking, clinically annotated biobank tissue, multicenter outcomes studies, prospective intervention studies, translational research, and health economics studies focused on value-based care questions.

Clinical Implications of Pituitary Adenomas Exhibiting Dual Transcription Factor Staining: A Case Series of 27 Patients.

OBJECTIVE: According to the 2017 World Health Organization classification of neuro-endocrine tumors, pituitary adenomas (PAs) are classified according to immunoexpression of the pituitary-specific transcription factors (TFs). A small subset of PAs exhibit multiple TF staining on immunohistochemistry and we present a series of 27 pathologically-confirmed cases of dual TF staining PAs (dsTF-PAs), and report clinically relevant implications. METHODS: A retrospective chart review of a multi-institutional database of patients with PAs surgically resected between 2008-2021 was performed. PAs expressing immunopositivity 2+ TFs. Patient demographics, neuro-imaging characteristics, histopathologic findings, and clinical data were collected. RESULTS: Twenty-seven patients had pathologically verified dsTF-PAs, of whom 17 were female (63%), with ages ranging from 20-84 years. Twenty-three (85.2%) patients harbored functional PAs, with acromegaly being the most common functional subtype (86.4%). The most common combination of TFs within a single tumor was PIT-1/SF-1 (85.2%). Six PAs exhibited Knosp cavernous sinus invasion grades of 3 or 4 and the Ki-67 labeling index was ≥3% in 6 patients (24.0%) and all stained for PIT-1/SF-1. Hormonal remission was achieved in 78% of functional dsTF-PAs. No PAs showed evidence of recurrence or progression over the mean follow-up period of 28.5 months. CONCLUSIONS: PAs exhibiting dsTF-PAs represent a small but clinically relevant diagnostic subset of PAs according to the 2021 World Health Organization criteria, as a majority are GH-producing. Precise classification using TF staining plays a key role in understanding the biology of these tumors. Favorable outcomes can be achieved in this subset of PAs with evolving TF classification.

A Prospective, Multicenter, Observational Study of Surgical vs Nonsurgical Management for Pituitary Apoplexy.

CONTEXT: Pituitary apoplexy (PA) has been traditionally considered a neurosurgical emergency, yet retrospective single-institution studies suggest similar outcomes among patients managed medically. OBJECTIVE: We established a multicenter, international prospective registry to compare presentation and outcomes in PA patients treated with surgery or medical management alone. METHODS: A centralized database captured demographics, comorbidities, clinical presentation, visual findings, hormonal status, and imaging features at admission. Treatment was determined independently by each site. Key outcomes included visual, oculomotor, and hormonal recovery, complications, and hospital length of stay. Outcomes were also compared based on time from symptom onset to surgery, and from admission or transfer to the treating center. Statistical testing compared treatment groups based on 2-sided hypotheses and P less than .05. RESULTS: A total of 100 consecutive PA patients from 12 hospitals were enrolled, and 97 (67 surgical and 30 medical) were evaluable. Demographics, clinical features, presenting symptoms, hormonal deficits, and imaging findings were similar between groups. Severe temporal visual field deficit was more common in surgical patients. At 3 and 6 months, hormonal, visual, and oculomotor outcomes were similar. Stratifying based on severity of visual fields demonstrated no difference in any outcome at 3 months. Timing of surgery did not affect outcomes. CONCLUSION: We found that medical and surgical management of PA yield similar 3-month outcomes. Although patients undergoing surgery had more severe visual field deficits, we could not clearly demonstrate that surgery led to better outcomes. Even without surgery, apoplectic tumor volumes regress substantially within 2 to 3 months, indicating that surgery is not always needed to reduce mass effect.

Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

OBJECTIVE: Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied. METHODS: Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated. RESULTS: Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group. CONCLUSIONS: CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

Needs Assessment of Non-core Content for Podcasts in Emergency Medicine.

Study objective The purpose of this study was to assess the use of podcasts among emergency medicine (EM) students, residents, and attending physicians for non-core content. Methods A survey was administered to medical students interested in emergency medicine, current residents of emergency medicine, and attending physicians to determine which podcasts, if any, they listen to and how often. The purpose of listening to these podcasts was also evaluated and determined it was to learn the non-core content of the specialty. The survey was administered online via multiple platforms including Google Forms (Google, Inc., Mountain View, CA), email, and Twitter (San Francisco, CA). The survey was also distributed via messaging application and word of mouth. Results There were 52 responses that were received on the survey. Of the respondents, 73.1% (N = 38) stated that they do listen to medical podcasts. Of these listeners, 21.2% (N = 11) stated that they listen to them once a year, 15.4% (N = 8) once a month, 11.5% (N = 6) once every two weeks, 19.2% (N = 10) weekly, 11.5% (N = 6) 1-2 days per week, 5.8% (N = 3) 3-4 days per week, 5.8% (N = 3) 5-6 days per week, and 9.6% (N = 5) daily. Based on the 52 responses received, 30.8% (N = 16) stated that they listen to them as a supplement to other sources of foundational content, 25% (N = 13) for general interest, 28.8% (N = 15) for entertainment, 7.7% (N = 4) as a primary resource to learn foundational content in their specialty, and 7.7% (N = 4) other. Based on the data metrics, 51.9% (N = 27) stated that 1-5 of the medical podcasts they listen to discuss the practice of emergency medicine, 44.2% (N = 23) stated that none do, and 3.8% (N = 2) stated that more than 10 do. The list of emergency medicine podcasts being listened to are as follows: EMplify, EM:RAP, EM Over Easy, EM Clerkship, Core EM, EM Basic, EMA, EM Cases, Internet Book of Critical Care, Pharm So Hard, EMCRIT, EM Board Bombs, PEM Rules, and REBEL CAST. When asked how important medical podcasts are for learning within the specialty, 44.2% (N = 23) reported not important, 26.9% (N = 14) reported somewhat important, and 28.8% (N = 15) reported very important. When asked how important medical podcasts are for learning outside the specialty, 40% (N = 20) reported not important, 48% (N = 24) reported somewhat important, and 12% (N = 6) stated very important. When asked if their program includes medical education podcasts as part of their curriculum, 18.4% (N = 9) responded yes, while 81.6% (N = 40) responded no. When asked if they believe medical education podcasts should be included as part of their curriculum, 52% (N = 26) stated yes, while 48% (N = 24) stated no. Conclusion Based on the results of the survey, roughly three-quarters of the surveyees listen to medical podcasts. Of the respondents, 38.5% (N = 20) stated that they listen to these podcasts as some form of supplement to learning content (7.7% (N = 4) primary and 30.8% (N = 16) supplementary), which explains the rising availability of the number of podcasts related to emergency medicine. Of the respondents stating that medical podcasts should be included in their curriculum, 52% (N = 26) signifies the importance of quality learning that these medical podcasts provide to their listeners.

Targeting the Tyrosine Kinase 2 (TYK2) Pseudokinase Domain: Discovery of the Selective TYK2 Inhibitor ABBV-712.

Tyrosine kinase 2 (TYK2) is a nonreceptor tyrosine kinase that belongs to the JAK family also comprising JAK1, JAK2, and JAK3. TYK2 is an attractive target for various autoimmune diseases as it regulates signal transduction downstream of IL-23 and IL-12 receptors. Selective TYK2 inhibition offers a differentiated clinical profile compared to currently approved JAK inhibitors. However, selectivity for TYK2 versus other JAK family members has been difficult to achieve with small molecules that inhibit the catalytically active kinase domain. Successful targeting of the TYK2 pseudokinase domain as a strategy to achieve isoform selectivity was recently exemplified with deucravacitinib. Described herein is the optimization of selective TYK2 inhibitors targeting the pseudokinase domain, resulting in the discovery of the clinical candidate ABBV-712 (21).

Pituitary adenoma or neuroendocrine tumour: the need for an integrated prognostic classification.

In the 2022 fifth edition of the WHO Classification of Endocrine Tumours and of Central Nervous System Tumours, pituitary adenomas are reclassified as neuroendocrine tumours (NETs). This change confers an oncology label to neoplasms that are overwhelmingly benign. A comprehensive clinical classification schema is required to guide prognosis, therapy and outcomes for all patients with pituitary adenomas. Pituitary adenomas and NETs exhibit some morphological and ultrastructural similarities. However, unlike NETs, pituitary adenomas are highly prevalent, yet indolent and rarely become malignant. This Perspective presents the outcomes of an interdisciplinary international workshop that addressed the merit and clinical implications of the classification change of pituitary adenoma to NET. Many non-histological factors provide mechanistic insight and influence the prognosis and treatment of pituitary adenoma. We recommend the development of a comprehensive classification that integrates clinical, genetic, biochemical, radiological, pathological and molecular information for all anterior pituitary neoplasms.

White-tailed deer (Odocoileus virginianus) fawn survival and the influence of landscape characteristics on fawn predation risk in the Southern Appalachian Mountains, USA.

In the Southern Appalachian region of the United States, harvest data has indicated the occurrence of low deer densities while exposing a trend of declining white-tailed deer (Odocoileus virginianus) populations over the past several decades in northern Georgia. A triumvirate of increasing fawn predator populations reside in the Southern Appalachian Mountains including coyotes (Canis latrans), black bears (Ursus americanus) and bobcats (Lynx rufus). This region is also characterized by a homogenous landscape composed of mature forests and sparse understory vegetation, likely lacking adequate cover to offer fawns refugia from predators. Our objectives were to estimate survival and cause-specific mortality rates of fawns while assessing a possible link between mortality risk, intrinsic fawn characteristics (i.e., birth mass, Julian birth date, sibling status), and landscape features within fawn usage areas. During 2018-2020, we radio-collared 71 fawns within the Chattahoochee National Forest of northern Georgia, USA and monitored survival to 12 weeks of age. We observed low fawn survival (cumulative = 0.157, 95% CI = 0.091-0.273; vaginal implant transmitter = 0.196, 95% CI = 0.096-0.403) with predation as the leading cause of all known mortalities (45 of 55 mortalities; 82%) due primarily to coyotes (n = 22), black bears (n = 12), and bobcats (n = 7). Relationships between landscape features and fawn predation risk were minimal with only one informative covariate. Increasing amounts of early successional land cover within fawn usage areas decreased fawn mortality risk within the first 20 days of life, but elevated mortality risk thereafter. All fawns with any amount of early successional land cover in their usage areas died of predation (n = 13) at various time intervals, suggesting limited areas of potential fawning cover may be targeted by predators. However, fawn predation risk seemed to be high regardless of landscape covariates due to the limited number of surviving fawns. Coyote-caused mortality occurred over a longer period at a consistently higher magnitude than all other forms of mortality, indicating possible delayed prey-switching behavior and coyote predation as an important factor of fawn survival. The low recruitment of fawns influenced by high predation rates and homogenous habitat conditions is likely the cause of deer population declines in the region.

Characteristics of Emergency Medicine Residency Programs With Unfilled Positions in the 2023 Match.

STUDY OBJECTIVE: The unprecedented number of unfilled emergency medicine post-graduate year 1 (PGY-1) residency positions in the 2023 National Resident Matching Program shocked the emergency medicine community. This study investigates the association between emergency medicine program characteristics and the likelihood of unfilled positions in the 2023 Match. METHODS: This cross-sectional, observational study examined 2023 National Resident Matching Program data, focusing on program type, length, location, size, proximity to other programs, previous American Osteopathic Association (AOA) accreditation, first accreditation year, and emergency department ownership structure. We constructed a generalized linear mixed model with a logistic linking function to determine predictors of unfilled positions. RESULTS: A total of 554 of 3,010 (18.4%) PGY-1 positions at 131 of 276 (47%) emergency medicine programs went unfilled in the 2023 Match. In our model, predictors included having unfilled positions in the 2022 Match (odds ratio [OR] 48.14, 95% confidence interval [CI] 21.04 to 110.15), smaller program size (less than 8 residents, OR 18.39, 95% CI 3.90 to 86.66; 8 to 10 residents, OR 6.29, 95% CI 1.50 to 26.28; 11 to 13 residents, OR 5.88, 95% CI 1.55 to 22.32), located in the Mid Atlantic (OR 14.03, 95% CI 2.56 to 77.04) area, prior AOA accreditation (OR 10.13, 95% CI 2.82 to 36.36), located in the East North Central (OR 6.94, 95% CI 1.25 to 38.47) area, and corporate ownership structure (OR 3.21, 95% CI 1.06 to 9.72). CONCLUSION: Our study identified 6 characteristics associated with unfilled emergency medicine residency positions in the 2023 Match. These findings may be used to guide student advising and inform decisions by residency programs, hospitals, and national organizations to address the complexities of residency recruitment and implications for the emergency medicine workforce.

Emergency provider preference for powered intraosseous devices and satisfaction with features improving safety, reliability, and ease-of-use.

BACKGROUND: Powered intraosseous (IO) systems are valuable devices for emergent situations, with limited data on user preferences. A simulation/survey-based study was conducted among emergency medical service (EMS) providers to evaluate attitudes toward general powered IO system features to measure preferences/satisfaction for the most-commonly used and a novel powered IO system (with a passive safety needle, battery life indicator, and snap-securement/dressing). RESEARCH DESIGN AND METHODS: Forty-two EMS providers completed a simulated activity using both powered IO systems and a 30-item questionnaire, including multiple choice, free-text, ranking, and Likert-like questions. Ranking scores were reported using a scale of 0 (least important/satisfactory) to 100 (most important/satisfactory). Statistical significances were evaluated via Wilcoxon signed-rank sum test. RESULTS: Providers indicated driver performance (mean score ± SD; 77.8 ± 27.5) and IO needle safety mechanism (63.1 ± 27.9) as the most important features. Participants reported significantly higher (p < 0.001) satisfaction with the novel IO system overall, and its needle safety, battery life indicator, securement/dressing, and ease-of-use. Powered driver performance satisfaction was similar and favorable for the novel (88.1 ± 18.2) and traditional (87.1 ± 15.3) systems. CONCLUSIONS: These findings highlight the value of clinician/user input and demonstrate EMS providers are more satisfied with a powered IO system featuring design elements intended to enhance safety and ease-of-use.

Genetically engineered human pituitary corticotroph tumor organoids exhibit divergent responses to glucocorticoid receptor modulators.

Cushing's disease (CD) is a serious endocrine disorder attributed to an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that that subsequently leads to chronic hypercortisolemia. PitNET regression has been reported following treatment with the investigational selective glucocorticoid receptor (GR) modulator relacorilant, but the mechanisms behind that effect remain unknown. Human PitNET organoid models were generated from induced human pluripotent stem cells (iPSCs) or fresh tissue obtained from CD patient PitNETs (hPITOs). Genetically engineered iPSC derived organoids were used to model the development of corticotroph PitNETs expressing USP48 (iPSCUSP48) or USP8 (iPSCUSP8) somatic mutations. Organoids were treated with the GR antagonist mifepristone or the GR modulator relacorilant with or without somatostatin receptor (SSTR) agonists pasireotide or octreotide. In iPSCUSP48 and iPSCUSP8 cultures, mifepristone induced a predominant expression of SSTR2 with a concomitant increase in ACTH secretion and tumor cell proliferation. Relacorilant predominantly induced SSTR5 expression and tumor cell apoptosis with minimal ACTH induction. Hedgehog signaling mediated the induction of SSTR2 and SSTR5 in response to mifepristone and relacorilant. Relacorilant sensitized PitNET organoid responsiveness to pasireotide. Therefore, our study identified the potential therapeutic use of relacorilant in combination with somatostatin analogs and demonstrated the advantages of relacorilant over mifepristone, supporting its further development for use in the treatment of Cushing's disease patients.

Endoscopic Endonasal Transsphenoidal Approach to Repair Cerebrospinal Fluid Rhinorrhea After an Anterior Clinoidectomy for Aneurysm Clipping: Series of 4 Cases.

BACKGROUND: Cerebrospinal fluid (CSF) rhinorrhea through a pneumatized optic strut is a known potential complication after an anterior clinoidectomy that is used to microsurgically clip a proximal internal carotid artery aneurysm. The original craniotomy site can be reopened to repair the skull base defect, but this technique has disadvantages. OBJECTIVE: To avoid a repeat craniotomy and address the limitations of a transcranial approach, a straightforward alternative was used for skull base repair-the binostril endoscopic endonasal transsphenoidal approach. METHODS: This retrospective case series describes the use of endoscopic transsphenoidal repair and outcomes for patients with CSF leaks after anterior clinoidectomy for aneurysm repair between January 1, 2015, and December 31, 2019. RESULTS: Four adult patients (3 women and 1 man) with a mean age of 59.5 years were reviewed. Skull base repair occurred on average 24 days (range, 4-75 days) after the index operation. After demucosalization of the parasellar sphenoid sinus, the fistula in the pneumatized optic strut was reconstructed with a free nasal mucosal graft with or without an autologous muscle graft. None of the patients developed a recurrent CSF leak at a mean follow-up of 12.5 months (range, 8-22 months), and none experienced complications. CONCLUSION: The endoscopic endonasal transsphenoidal approach was safe and effective for skull base repair in 4 patients with CSF rhinorrhea after an anterior clinoidectomy for aneurysm clipping.

Intraoperative confocal laser endomicroscopy: prospective in vivo feasibility study of a clinical-grade system for brain tumors.

OBJECTIVE: The authors evaluated the feasibility of using the first clinical-grade confocal laser endomicroscopy (CLE) system using fluorescein sodium for intraoperative in vivo imaging of brain tumors. METHODS: A CLE system cleared by the FDA was used in 30 prospectively enrolled patients with 31 brain tumors (13 gliomas, 5 meningiomas, 6 other primary tumors, 3 metastases, and 4 reactive brain tissue). A neuropathologist classified CLE images as interpretable or noninterpretable. Images were compared with corresponding frozen and permanent histology sections, with image correlation to biopsy location using neuronavigation. The specificities and sensitivities of CLE images and frozen sections were calculated using permanent histological sections as the standard for comparison. A recently developed surgical telepathology software platform was used in 11 cases to provide real-time intraoperative consultation with a neuropathologist. RESULTS: Overall, 10,713 CLE images from 335 regions of interest were acquired. The mean duration of the use of the CLE system was 7 minutes (range 3-18 minutes). Interpretable CLE images were obtained in all cases. The first interpretable image was acquired within a mean of 6 (SD 10) images and within the first 5 (SD 13) seconds of imaging; 4896 images (46%) were interpretable. Interpretable image acquisition was positively correlated with study progression, number of cases per surgeon, cumulative length of CLE time, and CLE time per case (p ≤ 0.01). The diagnostic accuracy, sensitivity, and specificity of CLE compared with frozen sections were 94%, 94%, and 100%, respectively, and the diagnostic accuracy, sensitivity, and specificity of CLE compared with permanent histological sections were 92%, 90%, and 94%, respectively. No difference was observed between lesion types for the time to first interpretable image (p = 0.35). Deeply located lesions were associated with a higher percentage of interpretable images than superficial lesions (p = 0.02). The study met the primary end points, confirming the safety and feasibility and acquisition of noninvasive digital biopsies in all cases. The study met the secondary end points for the duration of CLE use necessary to obtain interpretable images. A neuropathologist could interpret the CLE images in 29 (97%) of 30 cases. CONCLUSIONS: The clinical-grade CLE system allows in vivo, intraoperative, high-resolution cellular visualization of tissue microstructure and identification of lesional tissue patterns in real time, without the need for tissue preparation.

Assessment of the MAGIC recommendations in context of evolving evidence based on the use of PICC in ICU.

The goal of the 2015 Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) was to define indications and appropriate practices for peripherally inserted central catheters (PICC) use; however, MAGIC recommendations virtually reduced the use of PICC in hospital settings, including critical care. The aim of this review is to present an assessment of the MAGIC guidelines, considering contemporary evidence to date. The validity of the MAGIC recommendations and their applicability to current practice are called into question given important concerns with the methodology for their development (e.g. high volume of clinical scenarios for evaluation) and the supporting evidence used. There is a considerable amount of contemporary evidence not considered in MAGIC that reports on evolving practices, techniques, and technologies targeted to reduce complications associated with central venous access devices (CVADs). Recent evidence dictates that CVADs are necessary in the intensive care unit (ICU), and that PICCs are a safe, reliable, and appropriate type of central lines, which cannot be replaced in several ICU situations. In light of evolving evidence and practice, as well as the methodological concerns identified, the MAGIC guidelines should be revisited. It is also recommended to create a clinical assessment tool that identifies potential uses of specific CVADs, based on patient needs. The choice of the CVAD should be based on unique clinical considerations and current scientific evidence, not on fears informed by antiquated data.

Twisting Ovaries: Three Cases of Ovarian Torsion.

Ovarian torsion is a medical emergency that should be considered for every female presenting with abdominal pain. This series consists of three cases of females of varying ages presenting with abdominal pain who were all ultimately diagnosed with ovarian torsion. It highlights the variability in presentation, physical examination, and other factors related to the diagnosis.