Total brain volume is associated with severity of transverse sinus stenosis in idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a complex neurological condition characterized by symptoms of increased intracranial pressure of unclear etiology. While transverse sinus stenosis (TSS) is often present in patients with IIH, how and why it occurs remains unclear. METHODS: IIH patients and a set of age-matched normal controls were identified from our single-center tertiary care institution from 2016 to 2024. Brain MRIs before treatment were computationally segmented and parcellated using FreeSurfer software. Extent of TSS on MR venograms was graded using the Farb scoring system. Relationship between normalized brain volume, normalized brain-to-CSF volume, and TSS was investigated. Multiple linear regression was conducted to investigate the association between continuous variables, accounting for the covariates body mass index, sex, and age. RESULTS: In total, 84 IIH patients (mean age, 29.8 years; 87% female) and 15 normal controls (mean age, 28.1 years) were included. Overall, increasing/worsening TSS was found to be significantly associated with normalized total brain volume (p=0.018, R=0.179) and brain-to-CSF ratio volume (p=0.026, R=0.184). Additionally, there was a significant difference between controls and IIH patients with mild and severe stenosis regarding normalized total brain volume (ANCOVA, p=0.023) and brain-to-CSF ratio volume (ANCOVA, p=0.034). Likewise, IIH patients with severe TSS had a significantly higher brain-to-CSF volume compared with controls (p=0.038) and compared with IIH patients with mild TSS (p=0.038). CONCLUSIONS: These findings suggest that total brain volume is associated with extent of TSS, which may reflect extramural venous compression due to enlarged brain and/or venous hypertension with associated cerebral congestion/swelling.

Advancement in perioperative management of pituitary adenomas-Current concepts and best practices.

Pituitary adenomas are very common representing 18.1% of all brain tumors and are the second most common brain pathology. Transsphenoidal surgery is the mainstay of treatment for all pituitary adenomas except for prolactinomas which are primarily treated medically with dopamine agonists. A thorough endocrine evaluation of pituitary adenoma preoperatively is crucial to identify hormonal compromise caused by the large sellar mass, identifying prolactin-producing tumors and comorbidities associated with Cushing and acromegaly to improve patient care and outcome. Transsphenoidal surgery is relatively safe in the hands of experienced surgeons, but still carries a substantial risk of causing hypopituitarism that required close follow-up in the immediate postoperative period to decrease mortality. A multidisciplinary team approach with endocrinologists, ophthalmologists, and neurosurgeons is the cornerstone in the perioperative management of pituitary adenomas.

Decreasing the blood flow of non-compressible intra-abdominal organs with non-invasive transcutaneous electrical stimulation.

Non-invasive neuromodulation of non-compressible internal organs has significant potential for internal organ bleeding and blood-shift in aero/space medicine. The present study aims to investigate the potential influences of the non-invasive transcutaneous electrical nerve stimulation (TENS) on multiple non-compressible internal organs' blood flow. Porcine animal model (n = 8) was randomized for a total of 48 neuromodulation sessions with two different TENS stimulation frequencies (80 Hz, 10 Hz) and a placebo stimulation. A combination of two different electrode configurations (Abdominal-only or Abdominal and hind limb) were also performed. Intraarterial blood flow measurements were taken during pre and post-stimulation periods at the left renal artery, common hepatic artery, and left coronary artery. Intracranial, and extracranial arterial blood flows were also assessed with digital subtraction angiography. TENS with abdominal-only electrode configurations at 10 Hz demonstrated significant reductions in average peak blood flow velocity (APV) of the common hepatic artery (p = 0.0233) and renal arteries (p = 0.0493). Arterial pressures (p = 0.0221) were also significantly lower when renal APV was reduced. The outcome of the present study emphasises the potential use of TENS in decreasing the blood flow of non-compressible internal organs when the correct combination of electrodes configuration and frequency is used.

Evaluation of stem cell therapies in companion animal disease models: A concise review (2015-2023).

Companion animals in veterinary medicine develop multiple naturally occurring diseases analogous to human conditions. We previously reported a comprehensive review on the feasibility, safety, and biologic activity of using novel stem cell therapies to treat a variety of inflammatory conditions in dogs and cats (2008-2015) [1]. The purpose of this review is to provide an updated summary of current studies in companion animal disease models that have evaluated stem cell therapeutics that are relevant to human disease. Here we have reviewed the literature from 2015 to 2023 for publications on stem cell therapies that have been evaluated in companion animals, including dogs, cats, and horses. The review excluded case reports or studies performed in experimentally induced models of disease, studies involving cancer, or studies in purpose-bred laboratory species such as rodents. We identified 45 manuscripts meeting these criteria, an increase from 19 that were described in the previous review [1]. The majority of studies were performed in dogs (n=28), with additional studies in horses (n=9) and cats (n=8). Disease models included those related to musculoskeletal disease (osteoarthritis, tendon/ligament injury), neurologic disease (canine cognitive dysfunction, intervertebral disc disease, spinal cord injury) gingival/dental disease (gingivostomatitis), dermatologic disease (atopic dermatitis), chronic multi-drug resistant infections, ophthalmic disease (keratoconjunctivitis sicca, eosinophilic keratitis, immune mediated keratitis), cardiopulmonary disease (asthma, degenerative valve disease, dilated cardiomyopathy), gastrointestinal disease (inflammatory bowel disease, chronic enteropathy) and renal disease (chronic kidney disease). The majority of studies reported beneficial responses to stem cell treatment, with the exception of those related to more chronic processes such as spinal cord injury and chronic kidney disease. However, it should also be noted that 22 studies were open-label, baseline-controlled trials and only 12 studies were randomized and controlled, making overall study interpretation difficult. As noted in the previous review, improved regulatory oversight and consistency in manufacturing of stem cell therapies is needed. Enhanced understanding of the temporal course of disease processes using advanced -omics approaches may further inform mechanisms of action and help define appropriate timing of interventions. Future directions of stem cell-based therapies could include use of stem-cell derived extracellular vesicles, or cell conditioning approaches to direct cells to specific pathways that are tailored to individual disease processes and stages of illness.

The potential for senotherapy as a novel approach to extend life quality in veterinary medicine.

Cellular senescence, a condition where cells undergo arrest and can assume an inflammatory phenotype, has been associated with initiation and perpetuation of inflammation driving multiple disease processes in rodent models and humans. Senescent cells secrete inflammatory cytokines, proteins, and matrix metalloproteinases, termed the senescence associated secretory phenotype (SASP), which accelerates the aging processes. In preclinical models, drug interventions termed "senotherapeutics" selectively clear senescent cells and represent a promising strategy to prevent or treat multiple age-related conditions in humans and veterinary species. In this review, we summarize the current available literature describing in vitro evidence for senotheraputic activity, preclinical models of disease, ongoing human clinical trials, and potential clinical applications in veterinary medicine. These promising data to date provide further justification for future studies identifying the most active senotherapeutic combinations, dosages, and routes of administration for use in veterinary medicine.

Do microbes play a role in Alzheimer's disease?

Alzheimer's disease is a complex and progressive condition that affects essential neurological functions such as memory and reasoning. In the brain, neuronal loss, synaptic dysfunction, proteinopathy, neurofibrillary tangles, and neuroinflammation are the hallmarks of Alzheimer's disease pathophysiology. In addition, recent evidence has highlighted that microbes, whether commensal or pathogenic, also have the ability to interact with their host and to regulate its immune system, therefore participating in the exchanges that lead to peripheral inflammation and neuropathology. Because of this intimate relationship, bacteria, viruses, fungi, and protozoa have been implicated in the development of Alzheimer's disease. Here, we bring together current and most recent evidence of the role of microbes in Alzheimer's disease, raising burning questions that need to be addressed to guide therapeutic approaches and potential prophylactic strategies.

A dual-targeting succinate dehydrogenase and F1Fo-ATP synthase inhibitor rapidly sterilizes replicating and non-replicating Mycobacterium tuberculosis.

Mycobacterial bioenergetics is a validated target space for antitubercular drug development. Here, we identify BB2-50F, a 6-substituted 5-(N,N-hexamethylene)amiloride derivative as a potent, multi-targeting bioenergetic inhibitor of Mycobacterium tuberculosis. We show that BB2-50F rapidly sterilizes both replicating and non-replicating cultures of M. tuberculosis and synergizes with several tuberculosis drugs. Target identification experiments, supported by docking studies, showed that BB2-50F targets the membrane-embedded c-ring of the F1Fo-ATP synthase and the catalytic subunit (substrate-binding site) of succinate dehydrogenase. Biochemical assays and metabolomic profiling showed that BB2-50F inhibits succinate oxidation, decreases the activity of the tricarboxylic acid (TCA) cycle, and results in succinate secretion from M. tuberculosis. Moreover, we show that the lethality of BB2-50F under aerobic conditions involves the accumulation of reactive oxygen species. Overall, this study identifies BB2-50F as an effective inhibitor of M. tuberculosis and highlights that targeting multiple components of the mycobacterial respiratory chain can produce fast-acting antimicrobials.

Sex-specific effects of voluntary wheel running on behavior and the gut microbiota-immune-brain axis in mice.

Physical exercise has been positioned as a promising strategy to prevent and/or alleviate anxiety and depression, but the biological processes associated with its effects on mental health have yet to be entirely determined. Although the prevalence of depression and anxiety in women is about twice that of men, very few studies have examined whether physical exercise could affect mental health differently according to sex. This study examined, in singly-housed mice, the sex-specific effects of voluntary exercise on depressive- and anxiety-like behaviors as well as on different markers along the gut microbiota-immune-brain axis. Male and female C57BL/6N mice had voluntary access to running wheels in their home-cages for 24 days or were left undisturbed in identical home-cages without running wheels. Behaviors were then examined in the open field, splash, elevated plus maze, and tail suspension tests. Gene expression of pro-inflammatory cytokines, microglia activation-related genes, and tight junction proteins was determined in the jejunum and the hippocampus, while microbiota composition and predicted function were verified in cecum contents. Voluntary exercise reduced anxiety-like behaviors and altered grooming patterns in males exclusively. Although the exercise intervention resulted in changes to brain inflammatory activity and to cecal microbiota composition and inferred function in both sexes, reductions in the jejunal expression of pro-inflammatory markers were observed in females only. These findings support the view that voluntary exercise, even when performed during a short period, is beneficial for mental and intestinal health and that its sex-specific effects on behavior could be, at least in part, related to some components of the gut microbiota-immune-brain axis.

Novel Expression of GLUT3, GLUT6 and GLUT10 in Equine Gluteal Muscle Following Glycogen-Depleting Exercise: Impact of Dietary Starch and Fat.

Horses have a slow rate of muscle glycogen repletion relative to other species for unknown reasons. Our aim was to determine the expression of glucose transporters (GLUT) and genes impacting GLUT4 expression and translocation in the gluteal muscle. Five fit Thoroughbred horses performed glycogen-depleting exercises on high-starch (HS, 2869 g starch/day) and low-starch, high-fat diets (LS-HF, 358 g starch/d) with gluteal muscle biopsies obtained before and after depletion and during repletion. Muscle glycogen declined by ≈30% on both diets with little increase during repletion on LS-HF. Transcriptomic analysis identified differential expression (DE) of only 2/12 genes impacting GLUT4 translocation (two subunits of AMP protein kinase) and only at depletion on LS-HF. Only 1/13 genes encoding proteins that promote GLUT4 transcription had increased DE (PPARGC1A at depletion LS-HF). GLUT4 comprised ≈30% of total GLUT mRNA expression at rest. Remarkably, by 72 h of repletion expression of GLUT3, GLUT6 and GLUT10 increased to ≈25% of total GLUT mRNA. Expression of GLUT6 and GLUT10 lagged from 24 h of repletion on HS to 72 h on LS-HF. Lacking an increase in GLUT4 gene expression in response to glycogen-depleting exercise, equine muscle increases GLUT3, GLUT6 and GLUT10 expression potentially to enhance glucose transport, resembling responses observed in resistance trained GLUT4-null mice.

Cerebellar axonopathy in Shivers horses identified by spatial transcriptomic and proteomic analyses.

BACKGROUND: Shivers in horses is characterized by abnormal hindlimb movement when walking backward and is proposed to be caused by a Purkinje cell (PC) axonopathy based on histopathology. OBJECTIVES: Define region-specific differences in gene expression within the lateral cerebellar hemisphere and compare cerebellar protein expression between Shivers horses and controls. ANIMALS: Case-control study of 5 Shivers and 4 control geldings ≥16.2 hands in height. METHODS: Using spatial transcriptomics, gene expression was compared between Shivers and control horses in PC soma and lateral cerebellar hemisphere white matter, consisting primarily of axons. Tandem-mass-tag (TMT-11) proteomic analysis was performed on lateral cerebellar hemisphere homogenates. RESULTS: Differences in gene expression between Shivers and control horses were evident in principal component analysis of axon-containing white matter but not PC soma. In white matter, there were 455/1846 differentially expressed genes (DEG; 350 ↓DEG, 105 ↑DEG) between Shivers and controls, with significant gene set enrichment of the Toll-Like Receptor 4 (TLR4) cascade, highlighting neuroinflammation. There were 50/936 differentially expressed proteins (DEP). The 27 ↓DEP highlighted loss of axonal proteins including intermediate filaments (5), myelin (3), cytoskeleton (2), neurite outgrowth (2), and Na/K ATPase (1). The 23 ↑DEP were involved in the extracellular matrix (7), cytoskeleton (7), redox balance (2), neurite outgrowth (1), signal transduction (1), and others. CONCLUSION AND CLINICAL IMPORTANCE: Our findings support axonal degeneration as a characteristic feature of Shivers. Combined with histopathology, these findings are consistent with the known distinctive response of PC to injury where axonal changes occur without a substantial impact on PC soma.

Type 2 polysaccharide storage myopathy in Quarter Horses is a novel glycogen storage disease causing exertional rhabdomyolysis.

BACKGROUND: Both type 1 (PSSM1) and type 2 polysaccharide storage myopathy (PSSM2) are characterised by aggregates of abnormal polysaccharide in skeletal muscle. Whereas the genetic basis for PSSM1 is known (R309H GYS1), the cause of PSSM2 in Quarter Horses (PSSM2-QH) is unknown and glycogen concentrations not defined. OBJECTIVES: To characterise the histopathological and biochemical features of PSSM2-QH and determine if an associated monogenic variant exists in genes known to cause glycogenosis. STUDY DESIGN: Retrospective case control. METHODS: Sixty-four PSSM2-QH, 30 PSSM1-QH and 185 control-QH were identified from a biopsy repository and clinical data, histopathology scores (0-3), glycogen concentrations and selected glycolytic enzyme activities compared. Coding sequences of 12 genes associated with muscle glycogenoses were identified from whole genome sequences and compared between seven PSSM2-QH and five control-QH. RESULTS: Exertional rhabdomyolysis in PSSM2-QH occurred predominantly in barrel racing and working cow/roping performance types and improved with regular exercise and a low starch/fat-supplemented diet. Histopathological scores, including the amount of amylase-resistant polysaccharide (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, control-QH 0 ± 0, p < 0.001), and glycogen concentrations (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, control-QH 80 ± 27 mmol/kg, p < 0.0001) were intermediate in PSSM2-QH with significant differences among groups. In PSSM2-QH, abnormal polysaccharide had a less filamentous ultrastructure than PSSM1-QH and phosphorylase and phosphofructokinase activities were normal. Seventeen of 30 PSSM2-QH with available pedigrees descended from one of three stallions within four generations. Of the 29 predicted high or moderate impact genetic variants identified in candidate genes, none were present in only PSSM2-QH and absent in control-QH. MAIN LIMITATIONS: Analyses of PSSM2-QH and PSSM1-QH were performed on shipped samples, controls on frozen samples. CONCLUSIONS: PSSM2-QH is a novel glycogen storage disorder that is not the result of a mutation in genes currently known to cause muscle glycogenoses in other species.

CONTEXTO: Ambos os tipos 1 e 2 de miopatia por acúmulo de polissacarídeo (PSSM) são caracterizados por agregados de polissacarídeos anormais no músculo esquelético. Enquanto a base genética do PSSM 1 é conhecida (R309H GYS1), a causa do PSSM2 em cavalos Quarto de Milha (PSSM2-QH) é desconhecida, e a concentração de glicogênio não é definida. OBJETIVOS: Identificar as características histopatológicas e bioquímicas do PSSM-QH e determinar se há uma variante monogênica em genes conhecidos por causar glicogenose. DELINEAMENTO DO ESTUDO: Caso controlado retrospectivo. METODOLOGIA: 64 PSSM2-QH, 30 PSSM1-QH e 185 QH controles foram identificados em um arquivo de dados. Informação clínica, achados histológicos (escala 0-3), concentração de glicogênio e atividade enzimática de algumas enzimas glicolíticas foram comparadas. Sequências codificadas de 12 genes associados com glicogenose muscular foram identificados nas sequências genômicas completas, e comparadas entre 7 PSSM2-QH e 5 QH controles. RESULTADOS: Rabdomiólise por exercício em PSSM2-QH ocorreu predominantemente em cavalos de corrida de tambor e cavalos de team roping/trabalho com gado, e melhorou com exercício regular e uma dieta com baixo amido e alta gordura. A escala histopatológica, incluindo a quantidade de polissacarídeos resistentes à amilase (PSSM2-QH 1.4 ± 0.6, PSSM1-QH 2.1 ± 0.3, controle-QH 0 ± 0, P < 0.001), e concentrações de glicogênio (PSSM2-QH 129 ± 62, PSSM1-QH 175 ± 9, controle-QH 80 ± 27 mmol/kg, P < 0.0001) foram intermediárias em PSSM2-QH com diferença significante entre grupos. Em PSSM2-QH, polissacarídeo anormal teve uma ultraestrutura menos filamentosa do que PSSM1-QH e as atividades de fosforilase e fosfofrutoquinase foram normais. Dezessete dos 30 PSSM2-QH com pedigree disponível descendiam de 1 de 3 garanhões dentro de 4 gerações. Das 29 variações genéticas preditas a terem impacto moderado ou alto como genes candidatos, nenhuma estava presente apenas em PSSM2-QH e ausente no grupo controle-QH. PRINCIPAIS LIMITAÇÕES: As análises feitas nas amostras de PSSM2-QH e PSSM1-QH foram realizadas em amostras enviadas por correio, e as amostras dos animais controles eram amostras congeladas. CONCLUSÕES: PSSM2-QH é uma nova doença por acúmulo de glicogênio que não é o resultado de uma mutação nos genes conhecidos por causarem glicogenose muscular em outras espécies.

FLUORESCE: A Pilot Randomized Clinical Trial of Fluoxetine for Vision Recovery After Acute Ischemic Stroke.

BACKGROUND: Poststroke homonymous hemianopia is disabling, and complete spontaneous recovery is rare. In this randomized, placebo-controlled, double-blind, pilot clinical trial, we tested whether fluoxetine enhances vision recovery after stroke. METHODS: We randomized 17 consecutive adults 1:1 to 90 days of fluoxetine 20 mg daily vs placebo within 10 days of an ischemic stroke causing isolated homonymous hemianopia. The primary end point was percent improvement in 24-2 automated perimetry at 6 months. Twelve participants completed the study. Clinical trial registration NCT02737930. RESULTS: Intention-to-treat analysis of the primary end point, percent improvement in perimetric mean deviation, showed a nonsignificant benefit of fluoxetine (64.4%, n = 5) compared with placebo (26.0%, n = 7, one-tailed 95% confidence interval (CI) = (-2.13, ∞), P = 0.06). The original blind field completely recovered in 60% receiving fluoxetine and 14% receiving placebo (odds ratio = 7.22, one-tailed 95% CI = (0.50, ∞)). CONCLUSION: These results suggest a trend in favor of fluoxetine for vision recovery after stroke and have the potential to inform the design of a larger multicenter trial.

Splitting the anterior mitral leaflet impairs left ventricular function in an ovine model.

OBJECTIVES: During mitral valve replacement, the anterior mitral leaflet is usually resected or modified. Anterior leaflet splitting seems the least disruptive modification. Reattachment of the modified leaflet to the annulus reduces the annulopapillary distance. The goal of this study was to quantify the acute effects on left ventricular function of splitting the anterior mitral leaflet and shortening the annulopapillary distance. METHODS: In 6 adult sheep, a wire was placed around the anterior leaflet and exteriorized through the left ventricular wall to enable splitting the leaflet in the beating heart. Releasable snares to reduce annulopapillary distance were likewise positioned and exteriorized. A mechanical mitral prosthesis was inserted to prevent mitral incompetence during external manipulations of the native valve. Instantaneous changes in left ventricular function were recorded before and after shortening the annulopapillary distance, then before and after splitting the anterior leaflet. RESULTS: After splitting the anterior leaflet, preload recruitable stroke work, stroke work, stroke volume, cardiac output, left ventricular end systolic pressure and mean pressure were significantly decreased by 26%, 23%, 12%, 9%, 15% and 11%, respectively. Shortening the annulopapillary distance was associated with significant decreases in the end systolic pressure volume relationship, preload recruitable stroke work, stroke work and left ventricular end systolic pressure by 67%, 33%, 15% and 13%, respectively. Shortening the annulopapillary distance after splitting the leaflet had no significant effect. CONCLUSIONS: Splitting the anterior mitral leaflet acutely impaired left ventricular contractility and haemodynamics in an ovine model. Shortening the annulopapillary distance after leaflet splitting did not further impair left ventricular function.

Enriched Pathways of Calcium Regulation, Cellular/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis.

Certain Standardbred racehorses develop recurrent exertional rhabdomyolysis (RER-STD) for unknown reasons. We compared gluteal muscle histopathology and gene/protein expression between Standardbreds with a history of, but not currently experiencing rhabdomyolysis (N = 9), and race-trained controls (N = 7). Eight RER-STD had a few mature fibers with small internalized myonuclei, one out of nine had histologic evidence of regeneration and zero out of nine degeneration. However, RER-STD versus controls had 791/13,531 differentially expressed genes (DEG). The top three gene ontology (GO) enriched pathways for upregulated DEG (N = 433) were inflammation/immune response (62 GO terms), cell proliferation (31 GO terms), and hypoxia/oxidative stress (31 GO terms). Calcium ion regulation (39 GO terms), purine nucleotide metabolism (32 GO terms), and electron transport (29 GO terms) were the top three enriched GO pathways for down-regulated DEG (N = 305). DEG regulated RYR1 and sarcoplasmic reticulum calcium stores. Differentially expressed proteins (DEP ↑N = 50, ↓N = 12) involved the sarcomere (24% of DEP), electron transport (23%), metabolism (20%), inflammation (6%), cell/oxidative stress (7%), and other (17%). DEP included ↑superoxide dismutase, ↑catalase, and DEP/DEG included several cysteine-based antioxidants. In conclusion, gluteal muscle of RER-susceptible Standardbreds is characterized by perturbation of pathways for calcium regulation, cellular/oxidative stress, inflammation, and cellular regeneration weeks after an episode of rhabdomyolysis that could represent therapeutic targets.

Prolactin at moderately increased levels confers a neuroprotective effect in non-secreting pituitary macroadenomas.

CONTEXT: Prolactin, a hormone synthesized by the anterior pituitary gland demonstrates promise as a neuroprotective agent, however, its role in humans and in vivo during injury is not fully understood. OBJECTIVE: To investigate whether elevated levels of prolactin attenuate injury to the retinal nerve fiber layer (RNFL) following compression of the optic chiasm in patients with a prolactin secreting pituitary macroadenoma (i.e., prolactinoma). DESIGN SETTING AND PARTICIPANTS: A retrospective cross-sectional study of all pituitary macroadenoma patients treated at a single institution between 2009 and 2019. MAIN OUTCOME MEASURE(S): Primary outcome measures included RNFL thickness, mean deviation, and prolactin levels for both prolactin-secreting and non-secreting pituitary macroadenoma patients. RESULTS: Sixty-six patients met inclusion criteria for this study (14 prolactin-secreting and 52 non-secreting macroadenoma patients). Of 52 non-secreting macroadenoma patients, 12 had moderate elevation of prolactin secondary to stalk effect. Patients with moderate elevation in prolactin demonstrated increased RNFL thickness compared to patients with normal prolactin levels (p < 0.01). Additionally, a significant positive relation between increasing levels of prolactin and RNFL thickness was identified in patients with moderate prolactin elevation (R = 0.51, p-value = 0.035). No significant difference was identified between prolactinoma patients and those with normal prolactin levels. CONCLUSIONS: Moderately increased serum prolactin is associated with increased RNFL thickness when compared to controls. These associations are lost when serum prolactin is < 30 ng/ml or elevated in prolactinomas. This suggests a neuroprotective effect of prolactin at moderately increased levels in preserving retinal function during optic chiasm compression.

Analogue Mean Systemic Filling Pressure: a New Volume Management Approach During Percutaneous Left Ventricular Assist Device Therapy.

The absence of an accepted gold standard to estimate volume status is an obstacle for optimal management of left ventricular assist devices (LVADs). The applicability of the analogue mean systemic filling pressure (Pmsa) as a surrogate of the mean circulatory pressure to estimate volume status for patients with LVADs has not been investigated. Variability of flows generated by the Impella CP, a temporary LVAD, should have no physiological impact on fluid status. This translational interventional ovine study demonstrated that Pmsa did not change with variable circulatory flows induced by a continuous flow LVAD (the average dynamic increase in Pmsa of 0.20 ± 0.95 mmHg from zero to maximal Impella flow was not significant (p = 0.68)), confirming applicability of the human Pmsa equation for an ovine LVAD model. The study opens new directions for future translational and human investigations of fluid management using Pmsa for patients with temporary LVADs.

Extended Intraoperative Longitudinal 3-Dimensional Cone Beam Computed Tomography Imaging With a Continuous Multi-Turn Reverse Helical Scan.

OBJECTIVES: Cone beam computed tomography (CBCT) imaging is becoming an indispensable intraoperative tool; however, the current field of view prevents visualization of long anatomical sites, limiting clinical utility. Here, we demonstrate the longitudinal extension of the intraoperative CBCT field of view using a multi-turn reverse helical scan and assess potential clinical utility in interventional procedures. MATERIALS AND METHODS: A fixed-room robotic CBCT imaging system, with additional real-time control, was used to implement a multi-turn reverse helical scan. The scan consists of C-arm rotation, through a series of clockwise and anticlockwise rotations, combined with simultaneous programmed table translation. The motion properties and geometric accuracy of the multi-turn reverse helical imaging trajectory were examined using a simple geometric phantom. To assess potential clinical utility, a pedicle screw posterior fixation procedure in the thoracic spine from T1 to T12 was performed on an ovine cadaver. The multi-turn reverse helical scan was used to provide postoperative assessment of the screw insertion via cortical breach grading and mean screw angle error measurements (axial and sagittal) from 2 observers. For all screw angle measurements, the intraclass correlation coefficient was calculated to determine observer reliability. RESULTS: The multi-turn reverse helical scans took 100 seconds to complete and increased the longitudinal coverage by 370% from 17 cm to 80 cm. Geometric accuracy was examined by comparing the measured to actual dimensions (0.2 ± 0.1 mm) and angles (0.2 ± 0.1 degrees) of a simple geometric phantom, indicating that the multi-turn reverse helical scan provided submillimeter and degree accuracy with no distortion. During the pedicle screw procedure in an ovine cadaver, the multi-turn reverse helical scan identified 4 cortical breaches, confirmed via the postoperative CT scan. Directly comparing the screw insertion angles (n = 22) measured in the postoperative multi-turn reverse helical and CT scans revealed an average difference of 3.3 ± 2.6 degrees in axial angle and 1.9 ± 1.5 degrees in the sagittal angle from 2 expert observers. The intraclass correlation coefficient was above 0.900 for all measurements (axial and sagittal) across all scan types (conventional CT, multi-turn reverse helical, and conventional CBCT), indicating excellent reliability between observers. CONCLUSIONS: Extended longitudinal field-of-view intraoperative 3-dimensional imaging with a multi-turn reverse helical scan is feasible on a clinical robotic CBCT imaging system, enabling long anatomical sites to be visualized in a single image, including in the presence of metal hardware.