Citations

Abstract The sections in this article are: Vascular Anatomy and Fluid Phase Conduit Vessels to Bone Capillaries of Bone Fluid Transport Physiological Implications Bone Tissue Turnover Bone Remodeling Cells of Bone Mineral Phase Bone Repair Transport of Ions and Molecules in Bone Movement Into Bone From Bulk Extracellular Fluid (Influx) Efflux Methodology Indicator‐Dilution Methods Steady‐State Techniques (Volume of Distribution) Blood Flow Summary and Conclusions

Abstract The sections in this article are: Basal Vascular Resistance and Autoregulation Role of Myogenic Mechanism in Reactive Hyperemia Role of Myogenic Mechanism in Exercise Hyperemia Types of Skeletal Muscle Fibers Muscle Blood Flow During Exercise Oxygen Lack Lactic Acid, pH, and CO 2 Potassium Inorganic Phosphate Osmolarity Prostaglandins Adenosine and Adenine Nucleotides Intrinsic Neurons and Exercise Dilatation General Conclusions Mechanical Hindrance to Blood Flow in Skeletal Muscle Reactive Hyperemia Are Exercise and Reactive Hyperemia Due to the Same Mechanism(s)? Propagated Vasodilatation Sympathetic Vasomotor Outflow Noradrenergic Innervation of Resistance Vessels in Muscles Neuroeffector Junction α‐Adrenergic Activation Factors that Modulate Transmitter Output From Sympathetic Nerve Endings Metabolic Action Neurohumoral Action Reflex Regulation of Skeletal Muscle Resistance Vessels by Sympathetic Noradrenergic Nerves Carotid and Aortic Baroreflex Carotid and Aortic Chemoreflex Reflexes From the Heart and Lungs Diving Reflex Reflex From Receptors in Skeletal Muscles Rhythmic Exercise Isometric Exercise Influence of Sympathetic Noradrenergic Fibers on the Blood Flow to Active Muscles β 2 ‐Adrenergic Activation Cholinergic Vasodilator Nerves Role of Cholinergic Nerves in the Carotid Baroreflex Cholinergic Vasodilatation in Humans Histaminergic Vasodilatation Role of Histamine in the Vasodilatation Resulting From Reflex Inhibition of Sympathetic Outflow Conclusions

Abstract The sections in this article are: General Considerations Passive Changes in Splanchnic Blood Volume Active Constriction of Resistance and Capacitance Elements Active and Passive Components of Sympathetically Induced Change in Splanchnic Blood Volume Spleen Innervation Arterial Inflow Reflexly Mediated Changes in Splenic Blood Volume Conscious Dogs Humans Intestine Blood Flow and Blood Volume Sympathetic Adrenergic Nerve Activity Stress (Exercise, Excitement, and Body Heating) Effect of Food Intake Liver Hepatic Microcirculation Studies in Conscious Animals Hepatic Blood Flow Uptake and Release of Blood by the Liver Conclusion

Abstract The sections in this article are: Dynamics of the Renal Microcirculation Glomerular Capillary Pressure Glomerular Dynamics Single‐Nephron Filtration Rate Segmental Vascular Resistance Peritubule Capillary Dynamics Intrarenal Distribution of Blood Flow Cortical Blood Flow Medullary Blood Flow Autoregulation of Blood Flow Autoregulation in Various Renal Zones Localization of Resistance Changes Mechanisms of Autoregulation Additional Reading

Background/Objectives: The aim of this observational study was to collect hand measurements and anthropometric data in children aged 1–15 years of age to help the design of a pediatric skin electrode for electromyography-based neuromuscular monitoring. Methods: Data collection was performed at the Pediatric Department of the University of Debrecen Medical Centre between 1 December 2019 and 31 January 2021. After gaining written informed consent from the parents or legal representatives and verbal acceptance from age-appropriate (12–35 months) patients, a total of 153 children were enrolled. The following parameters were recorded: demographics (age, sex, weight, height, and hand dominance) and hand size parameters, defined as the distance between the following reference points: the ulnar groove and the midpoint of the hypothenar eminence (A); the midpoint of the hypothenar eminence and the first interphalangeal joint of the 5th finger (B); the ulnar groove and the midpoint of the thenar eminence (C); the midpoint of the thenar eminence and the interphalangeal joint of the thumb (D); the midpoint of the wrist crease and the tip of the third finger; wrist circumference (E); and forearm length. All measurements were made in centimeters (cm). Results: The children were divided into 4 groups (12–23 months, 2–5 years, 6–11 years and 12+ years). The number of children in the groups ranged between 6 and 16. The hand size parameters increased according to the children’s age (A: 4.3 ± 0.4, 5.0 ± 0.7, 6.3 ± 0.6, and 6.9 ± 1.0 cm; B: 3.2 ± 0.4, 4.1 ± 0.7, 5.0 ± 0.6, and 5.9 ± 0.6 cm; C: 3.0 ± 0.3, 3.6 ± 0.7, 4.1 ± 0.6, and 4.9 ± 0.6 cm; D: 4.1 ± 0.4, 4.8 ± 0.8, 6.2 ± 0.8, and 7.2 ± 0.9 cm; E: 10.1 ± 0.6, 12.0 ± 1.1, 15.3 ± 1.3, and 17.7 ± 1.7 cm, respectively, in the four groups, [mean ± SD]). The height of the children showed a closer correlation with hand size parameters (Pearson’s correlation coefficients: 0.702–0.961) than with age (0.665–0.904) or weight (0.675–0.863). The correlation was weaker when data were examined in prespecified age groups. Conclusions: The current pediatric hand size database provides previously unavailable information that was used in one manufacturer’s design, which may help with the future design of pediatric electrodes of electromyography-based neuromuscular monitors; this information may facilitate adoption of quantitative neuromuscular monitoring in routine pediatric anesthesia practice.

ABSTRACT Sjögren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytic infiltration and destruction of exocrine glands, commonly involving the salivary and lacrimal glands, leading to dry mouth and eyes. While SS primarily affects the upper gastrointestinal tract, this case presents a rare small intestine involvement. This patient was diagnosed with SS in 2018 with positive antinuclear antibodies (ANA), rheumatoid factor (RF), SSA antibodies, and salivary lip gland biopsy. By 2021, she developed unusual cyclic episodes of nausea, vomiting, and poor oral intake, resulting in significant weight loss and recurrent hospitalizations. She had frequent hospitalizations due to her recurrent symptoms. Evaluations included esophagogastroduodenoscopy (EGD) and colonoscopy, but pathology was nondiagnostic. Several abdominal and pelvic computed tomography (CT) scans demonstrated bladder edema, pancolitis, and terminal ileitis with mucosal hyperenhancement of the bowel and moderate ascites, likely inflammatory. Her gastric emptying study showed hypermotility. Multiple teams, including Rheumatology, Allergy/Immunology, Gastroenterology, Hematology, and Surgery, were involved. C1 esterase antigen was normal, ruling out hereditary angioedema. PET‐CT scan did not show lymphadenopathy or significant inflammation. Full biopsy for definitive diagnosis was deferred due to concerns of decreased healing with an edematous intestine. She was trialed on Icatibant without benefit. Differentials included lupus peritonitis, protein‐losing enteropathy, and SS intestinal lymphoma. She was discharged on a trial of empiric high‐dose steroids with Rheumatology follow‐up. Symptoms recurred with steroid tapering. Her complement levels decreased with flares and increased with treatment. Rituximab was added, leading to steady clinical improvement and reduced hospitalizations. Bowel involvement has been predominantly described in lupus, often referred to as lupus enteritis or bowel vasculitis. To our knowledge, this represents the first reported case of Sjögren's syndrome. Bowel biopsies are not typically subjected to routine immunohistochemical staining. Consequently, standard testing may be limited in detecting autoimmune processes. This case highlights the diagnostic challenges of SS‐related gastrointestinal manifestations and underscores the importance of considering autoimmune enteropathy, particularly in patients who respond to immunosuppressive therapy.

Abstract Disclosure: S. Saad-Omer: None. M. Stan: None. M.R. Castro: None. J. Brito: None. J.E. Hallanger-Johnson: None. M.M. Ryder: None. Background: Thyroid fine needle aspiration (FNA) is a widely utilized diagnostic tool for evaluating thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) provides a standardized framework for classifying cytologic findings and guiding management. This study retrospectively reviews thyroid FNA cases at a large academic institution to analyze the distribution of Bethesda classifications.Methods: A retrospective review was conducted of all thyroid FNA cases done in the department of Endocrinology at a large academic institution performed from January 1st 2019 to October 3rd 2023. Thyroid FNA results were divided into categories according to the Bethesda classification system, such as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm (FN), suspicious for malignancy, malignancy and non-diagnostic. FNA results that were not able to be classified were labelled as other.Results: A total of 3,291 thyroid FNA cases were included in the analysis. The distribution of cases across the Bethesda categories revealed a significant proportion of benign findings, with 73.6% classified as benign. This was followed by 8.1% follicular neoplasm, 6.56% Papillary Thyroid Cancer, 6.62% Non-diagnostic, 2.4% Atypical, and 2.3% Suspicious. 0.5% of FNA results were classified as other.Conclusion: Overall our cohort was found to have similar findings in terms of benign and confirmed PTC nodules compared to recent literature; however, the rate of atypical and non-diagnostic nodules was found to be lower. Presentation: Monday, July 14, 2025

Abstract Disclosure: C.A. Villavicencio Torres: None. S. Ahmadian: None. K. Moehnke: None. V.M. Fell: None. R.L. Taylor: None. S.K. Grebe: None. A.D. Maus: None. I. Bancos: None. Background: Evaluation of adrenal disorders relies on total cortisol measurements at baseline or during dynamic testing. Accurate cortisol assessment that avoids phlebotomy may simplify the work up of adrenal disorders, decrease healthcare costs, and improve patient experience. Objectives: We aimed to compare cortisol and dexamethasone concentrations between venipuncture-based (clinical) and capillary blood samples. Methodology: We conducted a cross-sectional study (July 2024-April 2025) of adults undergoing standard-of-care cortisol measurements. Capillary blood samples were collected alongside clinical samples. Capillary measurements included total cortisol and dexamethasone (mass spectrometry). Clinical samples were tested for total cortisol (Roche immunoassay) and dexamethasone (mass spectrometry). Results: Of 318 patients (243, 77% women, median age 53 years, IQR 39-66), 227 (71%) underwent dexamethasone suppression test (DST) and 88 (28%) cosyntropin stimulation test (CST). Capillary blood collection failed in 13 (4%) patients. In patients undergoing DST, median post-dexamethasone serum cortisol was 1.3 mcg/dL (IQR 0.8-2.2), and serum dexamethasone was 0.41 mcg/dL (IQR 0.27-0.59), while median capillary cortisol was 1.5 mcg/dL (IQR 1-2.5), and capillary dexamethasone was 0.33 mcg/dL (IQR 0.21-0.51). Capillary cortisol (r=0.95, 95% CI [0.93, 0.96], p<.0001) and capillary dexamethasone (r=0.93, 95% CI [0.90, 0.95], p<.0001) showed strong correlation with their respective clinical measurements. In patients undergoing CST, median baseline serum cortisol was 7.5 mcg/dL (IQR 5-10), and median baseline capillary cortisol was 8.5 mcg/dL (IQR 6-12). Median post-CST 60-minute serum cortisol was 23 mcg/dL (IQR 20-25), while capillary cortisol was 25 mcg/dL (IQR 21-28). Baseline (r=0.77, 95% CI [0.66, 0.85], p<.0001) and post-CST 60-minute capillary cortisol (r=0.88, 95% CI [0.81-92], p<.0001) strongly correlated with clinical measurements. Post-dexamethasone cortisol in paired DST samples showed that capillary measurements were higher than serum cortisol (median difference 0.20 mcg/dL (95% CI [0.12, 0.42], p<.0001), while paired capillary dexamethasone concentrations were lower than serum dexamethasone concentrations (median difference 0.04 mcg/dL (95% CI [0.03, 0.07], p<.0001). In CST, paired baseline capillary and serum cortisol concentrations were similar (median difference 0.10 mcg/dL, 95% CI [0.3, 0.3], p=.3660), while paired post-CST 60-minute capillary cortisol was higher than serum cortisol by a median of 2.8 mcg/dL (95% CI [2, 3.2], p<.0001). Conclusion: Capillary cortisol and dexamethasone concentrations demonstrate excellent correlation with venipuncture-based measurements. Following validation with at-home collection, capillary blood measurements may serve as an alternative for evaluating adrenal disorders. Presentation: Sunday, July 13, 2025

Abstract Disclosure: E.M. Lewiecki: Amgen Inc, Radius Health, Inc. K. Tough DeSapri: Amgen Inc, Radius Health, Inc. S. Denning: Amgen Inc, Radius Health, Inc. S.T. Harris: Amgen Inc, Radius Health, Inc. J.G. Sfeir: None. Y. Wang: Radius Health, Inc. J.A. Chiodo: Radius Health, Inc. F. Cosman: Amgen Inc, Biocon, Curateq, Enterabio, Radius Health, Inc, Theramex, UCB. Objectives: Studies have shown that the sequence of osteoporosis (OP) treatment can affect clinical outcome measures and likelihood of attaining therapeutic targets. The aim of this descriptive study was to evaluate the long-term OP treatment patterns in US patients prescribed anabolic therapies (ie, abaloparatide [ABL], teriparatide [TPTD], romosozumab [ROMO]). Methods: Anonymized patient claims data from a subset of ICON’s Symphony Health Patient Source Integrated Dataverse database was utilized. Men and women, aged ≥50 years with at least one prescription claim for ABL, TPTD, or ROMO from May 1, 2019 to April 30, 2021 were included. The index date was the date of the first anabolic treatment claim. For study inclusion, patients were required to have medical and pharmacy record information from 5 years prior to the start of, and 1 year after discontinuation of, anabolic treatment. Patients with a history of anabolic therapy in the 5 years prior to the index date were excluded. Results: 42,400 patients (ABL, n=16,673; TPTD, n=19,575; ROMO, n=6152) were included, of which 80%–90% were women. Persistence rates were low for all anabolic therapies. Overall mean (standard deviation [SD]) duration was 6.5 (5.8), 6.2 (5.6), and 6.0 (4.5) months for the ABL, TPTD, and ROMO groups, respectively, with approximately 45% of patients in the ABL and TPTD groups and 40% of patients in the ROMO group receiving therapy for ≤3 months. Only 18% (ABL) and 17% (TPTD) of patients received over 12 months of anabolic treatment, and 27% of patients in the ROMO group received over 9 months of treatment. In the 5 years prior to anabolic therapy, 35% (ABL), 34% (TPTD), and 47% (ROMO) of patients had prior OP treatment, with the majority having received an oral bisphosphonate (ABL, 26%; TPTD, 25%; ROMO, 21%) for a mean (SD) treatment duration of 15.8 (13.7), 15.5 (13.3), and 16.6 (14.4) months, respectively. The second most prescribed prior therapy was denosumab (ABL, 7%; TPTD, 7%; ROMO, 24%). In the 12 months after anabolic therapy, only 21% of patients in the ABL and TPTD groups received subsequent OP medication, the majority with either denosumab (9%) or oral BP (9%), and 49% of patients treated with ROMO received subsequent treatment, most of which was with denosumab (36%). Conclusions: The pattern of prescriptions of anabolic therapy in US adults identifies significant gaps in the treatment of skeletal fragility. Despite current clinical practice guidelines, the mean duration of anabolic treatment was less than 7 months, and a large majority of patients did not receive subsequent OP prescription following anabolic therapy. Additional research is needed to understand and overcome the obstacles in applying standard of care practices. Further analyses will reveal the clinical outcomes of these treatment patterns. Presentation: Saturday, July 12, 2025

Abstract Disclosure: K. Yu: None. J. Saini: None. E.J. Atkinson: None. S.J. Achenbach: None. V. Fell: None. I. Bancos: None. Background: Data on cognition in patients with primary aldosteronism (PA) are scarce. Mild autonomous cortisol secretion (MACS), defined based on post-dexamethasone cortisol >1.8 mcg/dL, is diagnosed in 20-30% of patients with PA. The impact of MACS on the cognition of patients with PA is unclear. Objectives: 1) to assess cognition in patients with PA versus sex-matched referent subjects with hypertension, 2) determine the differences in cognition of patients with PA (with and without MACS) and patients with MACS. Methods: A cross-sectional study, 2019-2023. Cognition was assessed by National Institute of Health Toolbox Cognition Battery and reported as T-score corrected for age, sex, race, and education. Only subjects with hypertension were included. Results: Cognitive assessment was performed in 52 patients with PA (including 11 patients with both PA and MACS, median age of 51 yrs, 30, 58% women), 47 patients with MACS (median age of 57 yrs, 31, 66% women), and 52 referent subjects (median age of 66 yrs, 30, 58% women). When compared to referents, and after age adjustment, patients with PA had lower cognition: fluid composite cognition β of -6.3 (P=0.014) and total composite of -5.6 (P=0.016). When compared to patients with MACS, and after age and sex adjustment, patients with PA had a similar total composite cognition score (β=3.6, P=0.108) but a higher fluid composite score (β=4.7, P=0.044). No differences in cognition were found between patients with PA with and without MACS, possibly due to low sample size. Conclusion: Patients with PA demonstrate lower cognition when compared to referents with hypertension. Patients with PA had a higher fluid cognition compared to patients with MACS. Future studies should delineate the impact of hyperaldosteronism vs MACS on cognition of patients with PA. Presentation: Monday, July 14, 2025