Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males.

Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown whether these dimorphisms control sex-typical behavior exclusively in one sex or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. Using a genetic strategy we developed, we have ablated one such dimorphic PR-expressing neuronal population located in the ventromedial hypothalamus (VMH). Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly defined, sexually dimorphic neuronal population in the brain. Moreover, we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes.

Predicting genome organisation and function with mechanistic modelling.

Fitting-free mechanistic models based on polymer simulations predict chromatin folding in 3D by focussing on the underlying biophysical mechanisms. This class of models has been increasingly used in conjunction with experiments to study the spatial organisation of eukaryotic chromosomes. Feedback from experiments to models leads to successive model refinement and has previously led to the discovery of new principles for genome organisation. Here, we review the basis of mechanistic polymer simulations, explain some of the more recent approaches and the contexts in which they have been useful to explain chromosome biology, and speculate on how they might be used in the future.

Use of an artificial intelligence-generated vascular severity score improved plus disease diagnosis in retinopathy of prematurity.

OBJECTIVE: To evaluate whether providing clinicians with an artificial intelligence-based vascular severity score (AI-VSS) improves consistency in diagnosis of plus disease in retinopathy of prematurity (ROP). DESIGN: This is a multi-reader diagnostic accuracy imaging study. PARTICIPANTS: Eleven ROP experts (4 pediatric ophthalmologists, 7 retina specialists), 9 of which had been in practice for 10 or more years. METHODS: Retcam (Natus Medical Incorporated) fundus images were obtained from premature infants during routine ROP screening as part of the Imaging and Informatics in ROP study between January 2012 and July 2020. From all available exams, a subset of 150 eye exams from 110 infants were selected for grading. An AI-VSS was assigned to each set of images using the i-ROP DL system. The clinicians were asked to diagnose plus disease for each exam and assign an estimated VSS (range 1-9) at baseline, and then again one month later with AI-VSS assistance. A reference standard diagnosis (RSD) was assigned to each eye exam from the i-ROP study based on 3 masked expert labels and the ophthalmoscopic diagnosis. MAIN OUTCOME MEASURE: Mean linearly weighted kappa for plus disease diagnosis compared to the RSD. Area under the receiver operating characteristic and precision-recall curves (AUROC, AUPR) for 1-9 labels compared to RSD for plus disease. RESULTS: Expert agreement improved significantly from substantial (κ: 0.69 [0.59, 0.75]) to near perfect (κ: 0.81 [0.71, 0.86]) when AI-VSS was integrated. Additionally, there was a significant improvement in plus disease discrimination as measured by mean [95% confidence interval] AUROC (0.94 [0.92, 0.96] to 0.98 [0.96, 0.99], difference: 0.04 [0.01, 0.06]) and AUPR (0.86 [0.81, 0.90] to 0.95 [0.91, 0.97], difference: 0.09 [0.03, 0.14]). CONCLUSIONS: Providing ROP clinicians with an AI-based measurement of vascular severity in ROP was associated with both improved plus disease diagnosis and improved continuous severity labeling, as compared to a reference standard diagnosis for plus disease. If implemented in practice, AI-VSS could reduce inter-observer variability and standardize treatment for infants with ROP.

Epidemiologic Evaluation of Retinopathy of Prematurity Severity in a Large Telemedicine Program in India Using Artificial Intelligence.

PURPOSE: Epidemiological changes in retinopathy of prematurity (ROP) depend on neonatal care, neonatal mortality, and the ability to carefully titrate and monitor oxygen. We evaluate whether an artificial intelligence (AI) algorithm for assessing ROP severity in babies can be used to evaluate changes in disease epidemiology in babies from South India over a 5-year period. DESIGN: Retrospective cohort study. PARTICIPANTS: Babies (3093) screened for ROP at neonatal care units (NCUs) across the Aravind Eye Care System (AECS) in South India. METHODS: Images and clinical data were collected as part of routine tele-ROP screening at the AECS in India over 2 time periods: August 2015 to October 2017 and March 2019 to December 2020. All babies in the original cohort were matched 1:3 by birthweight (BW) and gestational age (GA) with babies in the later cohort. We compared the proportion of eyes with moderate (type 2) or treatment-requiring (TR) ROP, and an AI-derived ROP vascular severity score (from retinal fundus images) at the initial tele-retinal screening exam for all babies in a district, VSS), in the 2 time periods. MAIN OUTCOME MEASURES: Differences in the proportions of type 2 or worse and TR-ROP cases, and VSS between time periods. RESULTS: Among BW and GA matched babies, the proportion [95% confidence interval {CI}] of babies with type 2 or worse and TR-ROP decreased from 60.9% [53.8%-67.7%] to 17.1% [14.0%-20.5%] (P < 0.001) and 16.8% [11.9%-22.7%] to 5.1% [3.4%-7.3%] (P < 0.001), over the 2 time periods. Similarly, the median [interquartile range] VSS in the population decreased from 2.9 [1.2] to 2.4 [1.8] (P < 0.001). CONCLUSIONS: In South India, over a 5-year period, the proportion of babies developing moderate to severe ROP has dropped significantly for babies at similar demographic risk, strongly suggesting improvements in primary prevention of ROP. These results suggest that AI-based assessment of ROP severity may be a useful epidemiologic tool to evaluate temporal changes in ROP epidemiology. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Trans-caval aspiration artherectomy/thrombectomy of large mobile plaques and thrombi in aortic arch and descending aorta.

Aspiration thrombectomy with the AngioVac is approved for percutaneous removal of thrombus in the venous system. While not approved for aspiration of thrombus or other mass in the left heart or arterial system, it has been used in that setting. Patients with left heart or arterial mass are often deemed unfavorable for surgery and treated conservatively. This may not be the best option for all patients, as some may have lesions that represent a short-term increased risk of complications, for which intervention and aspiration could be considered reasonable. Unfortunately, femoral arteries sizes often cannot accommodate the Angiovac current aspiration cannula dimensions. Here, we demonstrated trans-caval approach for aspiration thrombectomy of extensive aortic mobile plaque and thrombus.

Brainstem Modulation of Nociception by Periaqueductal Gray Neurons Expressing the µ-Opioid Receptor in Mice.

BACKGROUND: Pharmacologic manipulations directed at the periaqueductal gray have demonstrated the importance of the µ-opioid receptor in modulating reflexive responses to nociception. The authors hypothesized that a supraspinal pathway centered on neurons in the periaqueductal gray containing the µ-opioid receptor could modulate nociceptive and itch behaviors. METHODS: The study used anatomical, optogenetic, and chemogenetic approaches in male and female mice to manipulate µ-opioid receptor neurons in the periaqueductal gray. Behavioral assays including von Frey, Hargreaves, cold plantar, chloroquine-induced itch, hotplate, formalin-induced injury, capsaicin-induced injury, and open field tests were used. In separate experiments, naloxone was administered in a postsurgical model of latent sensitization. RESULTS: Activation of µ-opioid receptor neurons in the periaqueductal gray increased jumping (least-squares mean difference of -3.30 s; 95% CI, -6.17 to -0.44; P = 0.023; n = 7 or 8 mice per group), reduced itch responses (least-squares mean difference of 70 scratching bouts; 95% CI, 35 to 105; P < 0.001; n = 8 mice), and elicited modestly antinociceptive effects (least-squares mean difference of -0.7 g on mechanical and -10.24 s on thermal testing; 95% CI, -1.3 to -0.2 and 95% CI, -13.77 to -6.70, and P = 0.005 and P < 0.001, respectively; n = 8 mice). Last, the study uncovered the role of the periaqueductal gray in suppressing hyperalgesia after a postsurgical state of latent sensitization (least-squares mean difference comparing saline and naloxone of -12 jumps; 95% CI, -17 to -7; P < 0.001 for controls; and -2 jumps; 95% CI, -7 to 4; P = 0.706 after optogenetic stimulation; n = 7 to 9 mice per group). CONCLUSIONS: µ-Opioid receptor neurons in the periaqueductal gray modulate distinct nocifensive behaviors: their activation reduced responses to mechanical and thermal testing, and attenuated scratching behaviors, but facilitated escape responses. The findings emphasize the role of the periaqueductal gray in the behavioral expression of nociception using reflexive and noxious paradigms.

Motility induced phase separation of deformable cells.

Using a multi-phase field model, we examine how particle deformability, which is a proxy for cell stiffness, affects motility induced phase separation (MIPS). We show that purely repulsive deformable, i.e., squishy, cells phase separate more effectively than their rigid counterparts. This can be understood as due to the fact that deformability increases the effective duration of collisions. In addition, the dense regions become increasingly disordered as deformability increases. Our results contextualize the applicability of MIPS to biological systems and have implications for how cells in biological systems may self-organize.

Triclosan toxicity in a model cyanobacterium (Anabaena flos-aquae): Growth, photosynthesis and transcriptomic response.

Exposure to triclosan (TCS) has been reported to reduce photosynthetic pigments, suppress photosynthesis, and inhibit growth in both prokaryotic and eukaryotic algae including Anabaena flos-aquae (a model cyanobacterium). In particular, cyanobacteria are more sensitive to TCS toxicity compared to eukaryotic algae possibly due to the structural similarity to bacteria (target organisms); however, whether TCS exerts its toxicity to cyanobacteria by targeting signaling pathways of fatty acid biosynthesis as in bacteria remains virtually unknown, particularly at environmental exposure levels. With the complete genome sequence of A. flos-aquae presented in this study, the transcriptomic alterations and potential toxic mechanisms in A. flos-aquae under TCS stress were revealed. The growth, pigments and photosynthetic activity of A. flos-aquae were markedly suppressed following a 7-day TCS exposure at 0.5 µg/L but not 0.1 µg/L (both concentrations applied are environmentally relevant). The transcriptomic sequencing analysis showed that signaling pathways, such as biofilm formation - Pseudomonas aeruginosa, two-component system, starch and sucrose metabolism, and photosynthesis were closely related to the TCS-induced growth inhibition in the 0.5 µg/L TCS treatment. Photosynthesis systems and potentially two-component system were identified to be sensitive targets of TCS toxicity in A. flos-aquae. The present study provides novel insights on TCS toxicity at the transcriptomic level in A. flos-aquae.

A Concerted Enzymatic and Bioorthogonal Approach for Extra- and Intracellular Activation of Environment-Sensitive Ruthenium(II)-Based Imaging Probes and Photosensitizers.

In this article, we report a novel targeting strategy involving the combination of an enzyme-instructed self-assembly (EISA) moiety and a strained cycloalkyne to generate large accumulation of bioorthogonal sites in cancer cells. These bioorthogonal sites can serve as activation triggers in different regions for transition metal-based probes, which are new ruthenium(II) complexes carrying a tetrazine unit for controllable phosphorescence and singlet oxygen generation. Importantly, the environment-sensitive emission of the complexes can be further enhanced in the hydrophobic regions offered by the large supramolecular assemblies, which is highly advantageous to biological imaging. Additionally, the (photo)cytotoxicity of the large supramolecular assemblies containing the complexes was investigated, and the results illustrate that cellular localization (extracellular and intracellular) imposes a profound impact on the efficiencies of photosensitizers.

Foundational Considerations for Artificial Intelligence Using Ophthalmic Images.

IMPORTANCE: The development of artificial intelligence (AI) and other machine diagnostic systems, also known as software as a medical device, and its recent introduction into clinical practice requires a deeply rooted foundation in bioethics for consideration by regulatory agencies and other stakeholders around the globe. OBJECTIVES: To initiate a dialogue on the issues to consider when developing a bioethically sound foundation for AI in medicine, based on images of eye structures, for discussion with all stakeholders. EVIDENCE REVIEW: The scope of the issues and summaries of the discussions under consideration by the Foundational Principles of Ophthalmic Imaging and Algorithmic Interpretation Working Group, as first presented during the Collaborative Community on Ophthalmic Imaging inaugural meeting on September 7, 2020, and afterward in the working group. FINDINGS: Artificial intelligence has the potential to improve health care access and patient outcome fundamentally while decreasing disparities, lowering cost, and enhancing the care team. Nevertheless, substantial concerns exist. Bioethicists, AI algorithm experts, as well as the Food and Drug Administration and other regulatory agencies, industry, patient advocacy groups, clinicians and their professional societies, other provider groups, and payors (i.e., stakeholders) working together in collaborative communities to resolve the fundamental ethical issues of nonmaleficence, autonomy, and equity are essential to attain this potential. Resolution impacts all levels of the design, validation, and implementation of AI in medicine. Design, validation, and implementation of AI warrant meticulous attention. CONCLUSIONS AND RELEVANCE: The development of a bioethically sound foundation may be possible if it is based in the fundamental ethical principles of nonmaleficence, autonomy, and equity for considerations for the design, validation, and implementation for AI systems. Achieving such a foundation will be helpful for continuing successful introduction into medicine before consideration by regulatory agencies. Important improvements in accessibility and quality of health care, decrease in health disparities, and lower cost thereby can be achieved. These considerations should be discussed with all stakeholders and expanded on as a useful initiation of this dialogue.

Artificial Intelligence for Retinopathy of Prematurity: Validation of a Vascular Severity Scale against International Expert Diagnosis.

PURPOSE: To validate a vascular severity score as an appropriate output for artificial intelligence (AI) Software as a Medical Device (SaMD) for retinopathy of prematurity (ROP) through comparison with ordinal disease severity labels for stage and plus disease assigned by the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), committee. DESIGN: Validation study of an AI-based ROP vascular severity score. PARTICIPANTS: A total of 34 ROP experts from the ICROP3 committee. METHODS: Two separate datasets of 30 fundus photographs each for stage (0-5) and plus disease (plus, preplus, neither) were labeled by members of the ICROP3 committee using an open-source platform. Averaging these results produced a continuous label for plus (1-9) and stage (1-3) for each image. Experts were also asked to compare each image to each other in terms of relative severity for plus disease. Each image was also labeled with a vascular severity score from the Imaging and Informatics in ROP deep learning system, which was compared with each grader's diagnostic labels for correlation, as well as the ophthalmoscopic diagnosis of stage. MAIN OUTCOME MEASURES: Weighted kappa and Pearson correlation coefficients (CCs) were calculated between each pair of grader classification labels for stage and plus disease. The Elo algorithm was also used to convert pairwise comparisons for each expert into an ordered set of images from least to most severe. RESULTS: The mean weighted kappa and CC for all interobserver pairs for plus disease image comparison were 0.67 and 0.88, respectively. The vascular severity score was found to be highly correlated with both the average plus disease classification (CC = 0.90, P < 0.001) and the ophthalmoscopic diagnosis of stage (P < 0.001 by analysis of variance) among all experts. CONCLUSIONS: The ROP vascular severity score correlates well with the International Classification of Retinopathy of Prematurity committee member's labels for plus disease and stage, which had significant intergrader variability. Generation of a consensus for a validated scoring system for ROP SaMD can facilitate global innovation and regulatory authorization of these technologies.

Local Yield and Compliance in Active Cell Monolayers.

The rheology of biological tissue plays an important role in many processes, from organ formation to cancer invasion. Here, we use a multiphase field model of motile cells to simulate active microrheology within a tissue monolayer. When unperturbed, the tissue exhibits a transition between a solidlike state and a fluidlike state tuned by cell motility and deformability-the ratio of the energetic costs of steric cell-cell repulsion and cell-edge tension. When perturbed, solid tissues exhibit local yield-stress behavior, with a threshold force for the onset of motion of a probe particle that vanishes upon approaching the solid-to-liquid transition. This onset of motion is qualitatively different in the low and high deformability regimes. At high deformability, the tissue is amorphous when solid, it responds compliantly to deformations, and the probe transition to motion is smooth. At low deformability, the monolayer is more ordered translationally and stiffer, and the onset of motion appears discontinuous. Our results suggest that cellular or nanoparticle transport in different types of tissues can be fundamentally different and point to ways in which it can be controlled.

Preclosure of large bore venous access sites in patients undergoing transcatheter mitral replacement and repair.

OBJECTIVE: We aim to report on the efficacy and safety of large bore venous access (LBVA) preclosure with Perclose™ (Abbott Vascular Devices) suture-mediated device use following transcatheter edge-to-edge (TEER) and replacement (TMVR). BACKGROUND: Patients requiring TEER and TMVR require LBVA. Clinical outcome data on the use of suture-mediated devices for LBVA site closure are limited. METHODS: Between 2012 and 2019, 354 consecutive high-risk patients with mitral valvular heart disease underwent TEER (n = 287) with MitraClip and TMVR (n = 67) with Edwards Sapien Valves. Patients had LBVA with 24 or 16 French sheaths. All patients underwent preclosure of LBVA except for one that underwent manual hemostasis. RESULTS: There were no closure device failures. None of the cases required surgical repair of the access site following venous preclosure. Two cases had large hematomas (>6 cm) following Perclose in each group. Six cases had small hematomas (<6 cm and >2 cm) with three in each group. There was one major bleeding using Mitral Valve Academic Research Consortium 2 definition (retroperitoneal bleed from arterial puncture) unrelated to the venous closure. Transfusion related to vascular access complication was required in five cases. There were two immediate acute deep venous thromboses postprocedure; one of which occurred after preclosure. There were no arteriovenous malformations, pseudoaneurysms, or access site infections reported following Perclose. CONCLUSION: In this large sample size analysis, Proglide preclosure technique is a feasible and safe alternative approach to achieving hemostasis after removal of LBVA sheaths in patients undergoing TEER and TMVR. Randomized trials are needed to compare the different modalities of hemostasis.

Artificial intelligence at the national eye institute.

PURPOSE OF REVIEW: This review highlights the artificial intelligence, machine learning, and deep learning initiatives supported by the National Institutes of Health (NIH) and the National Eye Institute (NEI) and calls attention to activities and goals defined in the NEI Strategic Plan as well as opportunities for future activities and breakthroughs in ophthalmology. RECENT FINDINGS: Ophthalmology is at the forefront of artificial intelligence-based innovations in biomedical research that may lead to improvement in early detection and surveillance of ocular disease, prediction of progression, and improved quality of life. Technological advances have ushered in an era where unprecedented amounts of information can be linked that enable scientific discovery. However, there remains an unmet need to collect, harmonize, and share data in a machine actionable manner. Similarly, there is a need to ensure that efforts promote health and research equity by expanding diversity in the data and workforce. SUMMARY: The NIH/NEI has supported the development artificial intelligence-based innovations to advance biomedical research. The NIH/NEI has defined activities to achieve these goals in the NIH Strategic Plan for Data Science and the NEI Strategic Plan and have spearheaded initiatives to facilitate research in these areas.

Evaluation of a Deep Learning-Derived Quantitative Retinopathy of Prematurity Severity Scale.

PURPOSE: To evaluate the clinical usefulness of a quantitative deep learning-derived vascular severity score for retinopathy of prematurity (ROP) by assessing its correlation with clinical ROP diagnosis and by measuring clinician agreement in applying a novel scale. DESIGN: Analysis of existing database of posterior pole fundus images and corresponding ophthalmoscopic examinations using 2 methods of assigning a quantitative scale to vascular severity. PARTICIPANTS: Images were from clinical examinations of patients in the Imaging and Informatics in ROP Consortium. Four ophthalmologists and 1 study coordinator evaluated vascular severity on a scale from 1 to 9. METHODS: A quantitative vascular severity score (1-9) was applied to each image using a deep learning algorithm. A database of 499 images was developed for assessment of interobserver agreement. MAIN OUTCOME MEASURES: Distribution of deep learning-derived vascular severity scores with the clinical assessment of zone (I, II, or III), stage (0, 1, 2, or 3), and extent (<3 clock hours, 3-6 clock hours, and >6 clock hours) of stage 3 evaluated using multivariate linear regression and weighted κ values and Pearson correlation coefficients for interobserver agreement on a 1-to-9 vascular severity scale. RESULTS: For deep learning analysis, a total of 6344 clinical examinations were analyzed. A higher deep learning-derived vascular severity score was associated with more posterior disease, higher disease stage, and higher extent of stage 3 disease (P < 0.001 for all). For a given ROP stage, the vascular severity score was higher in zone I than zones II or III (P < 0.001). Multivariate regression found zone, stage, and extent all were associated independently with the severity score (P < 0.001 for all). For interobserver agreement, the mean ± standard deviation weighted κ value was 0.67 ± 0.06, and the Pearson correlation coefficient ± standard deviation was 0.88 ± 0.04 on the use of a 1-to-9 vascular severity scale. CONCLUSIONS: A vascular severity scale for ROP seems feasible for clinical adoption; corresponds with zone, stage, extent of stage 3, and plus disease; and facilitates the use of objective technology such as deep learning to improve the consistency of ROP diagnosis.

International Classification of Retinopathy of Prematurity, Third Edition.

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

105° field of view non-contact handheld swept-source optical coherence tomography.

We demonstrate a handheld swept-source optical coherence tomography (OCT) system with a 400 kHz vertical-cavity surface-emitting laser (VCSEL) light source, a non-contact approach, and an unprecedented single shot 105° field of view (FOV). We also implemented a spiral scanning pattern allowing real-time visualization with improved scanning efficiency. To the best of our knowledge, this is the widest FOV achieved in a portable non-contact OCT retinal imaging system to date. Improvements to the FOV may aid the evaluation of retinal diseases such as retinopathy of prematurity, where important vitreoretinal changes often occur in the peripheral retina.

Description and management of retinopathy of prematurity reactivation after intravitreal antivascular endothelial growth factor therapy.

PURPOSE OF REVIEW: To review the literature regarding reactivation of retinopathy of prematurity (ROP) after treatment with antivascular endothelial growth factor (anti-VEGF) agents. RECENT FINDINGS: Reactivation can occur after anti-VEGF or laser. Risk factors for reactivation include patient and disease-related factors. Various studies are evaluating the use of different anti-VEGF agents and reactivation rates. However, the definition of reactivation varies between studies. SUMMARY: The literature has varied definitions of reactivation, which is often used interchangeably with recurrence. It is important to recognize features of reactivation of ROP to appropriately manage patients and conduct clinical trials. The International Classification of ROP 3rd edition has established a consensus guideline regarding terminology describing reactivation.

Applications of Endoscopic Endonasal Surgery in Early Childhood: A Case Series.

INTRODUCTION: Endoscopic endonasal surgery (EES) has been slower to gain popularity in early childhood due to anatomical challenges. We sought to describe the safety and efficacy of EES in early childhood. METHODS: All patients younger than 7 years who underwent EES at a large Cranial Base Center from 2002 to 2019 were reviewed as a retrospective cohort study. RESULTS: Thirty-six patients underwent EES before the age of 7 years. Four patients had two-stage EES. Two patients required combined transcranial and endonasal approaches. The mean age at the time of initial surgery was 4 years (range: 1-6). Twenty patients were male, and 16 were female. Of 21 tumors intended for resection, 11 patients had gross total resections, and 10 had near total (>95% tumor removed) resections. Nine patients (43%) had recurrences, of which 6 were craniopharyngiomas (p = 0.01). There was no difference in recurrence rates based on the degree of resection (p = 0.67). Three cerebrospinal fluid (CSF) leaks occurred following primary EES (8%). Following an increase in nasoseptal flap usage (31-52%) and CSF diversion (15-39%) in 2008, there was only one CSF leak out of 23 patients (4 vs. 15%; p = 0.54). Postoperatively, 1 patient developed a permanent new cranial neuropathy, and 1 patient developed a permanent visual field cut. Six patients developed permanent postoperative panhypopituitarism, of which all were craniopharyngiomas (p < 0.001). The mean follow-up was 64 months. CONCLUSIONS: Early childhood EES is both safe and technically feasible for a variety of pathologies.

Parabrachial Complex: A Hub for Pain and Aversion.

The parabrachial nucleus (PBN) has long been recognized as a sensory relay receiving an array of interoceptive and exteroceptive inputs relevant to taste and ingestive behavior, pain, and multiple aspects of autonomic control, including respiration, blood pressure, water balance, and thermoregulation. Outputs are known to be similarly widespread and complex. How sensory information is handled in PBN and used to inform different outputs to maintain homeostasis and promote survival is only now being elucidated. With a focus on taste and ingestive behaviors, pain, and thermoregulation, this review is intended to provide a context for analysis of PBN circuits involved in aversion and avoidance, and consider how information of various modalities, interoceptive and exteroceptive, is processed within PBN and transmitted to distinct targets to signal challenge, and to engage appropriate behavioral and physiological responses to maintain homeostasis.