Frontal and anterior temporal hypometabolism post chemoradiation in head and neck cancer: A real-world PET study.

BACKGROUND AND PURPOSE: Adverse neurological effects after cancer therapy are common, but biomarkers to diagnose, monitor, or risk stratify patients are still not validated or used clinically. An accessible imaging method, such as fluorodeoxyglucose positron emission tomography (FDG PET) of the brain, could meet this gap and serve as a biomarker for functional brain changes. We utilized FDG PET to evaluate which brain regions are most susceptible to altered glucose metabolism after chemoradiation in patients with head and neck cancer (HNCa). METHODS: Real-world FDG PET images were acquired as standard of care before and after chemoradiation for HNCa in 68 patients. Linear mixed-effects voxelwise models assessed changes after chemoradiation in cerebral glucose metabolism quantified with standardized uptake value ratio (SUVR), covarying for follow-up time and patient demographics. RESULTS: Voxelwise analysis revealed two large clusters of decreased glucose metabolism in the medial frontal and polar temporal cortices following chemoradiation, with decreases of approximately 5% SUVR after therapy. CONCLUSIONS: These findings provide evidence that standard chemoradiation for HNCa can lead to decreased neuronal glucose metabolism, contributing to literature emphasizing the vulnerability of the frontal and anterior temporal lobes, especially in HNCa, where these areas may be particularly vulnerable to indirect radiation-induced injury. FDG PET shows promise as a sensitive biomarker for assessing these changes.

Gas Exchange in the Lung.

Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and remove carbon dioxide from blood in alveolar capillaries. In a lung model without ventilation and perfusion (V̇AQ̇) mismatch, alveolar partial pressures of oxygen and carbon dioxide are primarily determined by inspiratory pressures and alveolar ventilation. Regions with shunt or low ratios worsen arterial oxygenation while alveolar dead space and high lung units lessen CO2 elimination efficiency. Although less common, diffusion limitation might cause hypoxemia in some situations. This review covers the principles of lung gas exchange and therefore mechanisms of hypoxemia or hypercapnia. In addition, we discuss different metrics that quantify the deviation from ideal gas exchange.

PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm.

Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.

Lower cerebral oxygen utilization is associated with Alzheimer's disease-related neurodegeneration and poorer cognitive performance among apolipoprotein E ε4 carriers.

Oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) are markers of cerebral oxygen homeostasis and metabolism that may offer insights into abnormal changes in brain aging. The present study cross-sectionally related OEF and CMRO2 to cognitive performance and structural neuroimaging variables among older adults (n = 246, 74 ± 7 years, 37% female) and tested whether apolipoprotein E (APOE)-ε4 status modified these associations. Main effects of OEF and CMRO2 were null (p-values >0.06), and OEF interactions with APOE-ε4 status on cognitive and structural imaging outcomes were null (p-values >0.06). However, CMRO2 interacted with APOE-ε4 status on language (p = 0.002), executive function (p = 0.03), visuospatial (p = 0.005), and episodic memory performances (p = 0.03), and on hippocampal (p = 0.006) and inferior lateral ventricle volumes (p = 0.02). In stratified analyses, lower oxygen metabolism related to worse language (p = 0.02) and episodic memory performance (p = 0.03) among APOE-ε4 carriers only. Associations between CMRO2 and cognitive performance were primarily driven by APOE-ε4 carriers with existing cognitive impairment. Congruence across language and episodic memory results as well as hippocampal and inferior lateral ventricle volume findings suggest that APOE-ε4 may interact with cerebral oxygen metabolism in the pathogenesis of Alzheimer's disease and related neurodegeneration.

A Novel and Inexpensive Technique for High-Tension Tendon Clamping With Expandable Mesh Sleeving for In Vitro Foot Biomechanics Testing.

In vitro biomechanical testing is common in the field of orthopedics when novel devices are investigated prior to human trials. It is typically necessary to apply loads through tendons to simulate normal activities, such as walking during a foot and ankle study. However, attachment of tendons to linear actuators has proven challenging because of the tendency of clamps to either slip off or rupture the tendon. Various techniques have been utilized. Freeze clamping is generally accepted as the gold standard for very high load testing in excess of 3000 N, but is expensive, time-consuming, and requires significant ancillary equipment. Purely mechanical solutions such as metal jaw clamps, wire meshes, and others have been explored, but these techniques are either costly, have low load capacities, or have not proven to be reproducible. We have developed a novel tendon clamping technique that utilizes a slip-resistant polyester mesh sleeving that encases the tendon and is fixated at the bottom of the tendon/sleeve interaction with a giftbox suture. The loose end of the sleeving can then be tied in to the linear actuator or load cell apparatus using a timber hitch knot. The sleeving technique allows for loads of 2000-2500 N on the Achilles tendon, and is inexpensive, reproducible, and can be modified to apply loads to smaller tendons as well, though a length of tendon/sleeve overlap of at least 16 cm is required to reach maximum loads. This technique should assist researchers in integrating muscle forces into future biomechanical study designs.

Assessment of L5-S1 anterior lumbar interbody fusion stability in the setting of lengthening posterior instrumentation constructs: a cadaveric biomechanical study.

OBJECTIVE: Excessive stress and motion at the L5-S1 level can lead to degenerative changes, especially in patients with posterior instrumentation suprajacent to L5. Attention has turned to utilization of L5-S1 anterior lumbar interbody fusion (ALIF) to stabilize the lumbosacral junction. However, questions remain regarding the effectiveness of stand-alone ALIF in the setting of prior posterior instrumented fusions terminating at L5. The purpose of this study was to assess the biomechanical stability of an L5-S1 ALIF with increasing lengths of posterior thoracolumbar constructs. METHODS: Seven human cadaveric spines (T9-sacrum) were instrumented with pedicle screws from T10 to L5 and mounted to a 6 degrees-of-freedom robot. Posterior fusion construct lengths (T10-L5, T12-L5, L2-5, and L4-5) were instrumented to each specimen, and torque-fusion level relationships were determined for each construct in flexion-extension, axial rotation, and lateral bending. A stand-alone L5-S1 ALIF was then instrumented, and L5-S1 motion was measured as increasing pure moments (2 to 12 Nm) were applied. Motion reduction was calculated by comparing L5-S1 motion across the ALIF and non-ALIF states. RESULTS: The average motion at L5-S1 in axial rotation, flexion-extension, and lateral bending was assessed for each fusion construct with and without ALIF. After adding ALIF to a posterior fusion, L5-S1 motion was significantly reduced relative to the non-ALIF state in all but one fused surgical condition (p < 0.05). Longer fusions with ALIF produced larger L5-S1 motions, and in some cases resulted in motions higher than native state motion. CONCLUSIONS: Posterior fusion constructs up to L4-5 could be appropriately stabilized by a stand-alone L5-S1 ALIF when using a nominal threshold of 80% reduction in native motion as a potential positive indicator of fusion. The results of this study allow conclusions to be drawn from a biomechanical standpoint; however, the clinical implications of these data are not well defined. These findings, when taken in appropriate clinical context, can be used to better guide clinicians seeking to treat L5-S1 pathology in patients with prior posterior thoracolumbar constructs.

Evaluating stability of the craniovertebral junction after unilateral C1 lateral mass resection: implications for the direct lateral approach.

OBJECTIVE: The direct lateral approach is an alternative to the transoral or endonasal approaches to ventral epidural lesions at the lower craniocervical junction. In this study, the authors performed, to their knowledge, the first in vitro biomechanical evaluation of the craniovertebral junction after sequential unilateral C1 lateral mass resection. The authors hypothesized that partial resection of the lateral mass would not result in a significant increase in range of motion (ROM) and may not require internal stabilization. METHODS: The authors performed multidirectional in vitro ROM testing using a robotic spine testing system on 8 fresh cadaveric specimens. We evaluated ROM in 3 primary movements (axial rotation [AR], flexion/extension [FE], and lateral bending [LB]) and 4 coupled movements (AR+E, AR+F, LB + left AR, and LB + right AR). Testing was performed in the intact state, after C1 hemilaminectomy, and after sequential 25%, 50%, 75%, and 100% C1 lateral mass resection. RESULTS: There were no significant increases in occipital bone (Oc)-C1, C1-2, or Oc-C2 ROM after C1 hemilaminectomy and 25% lateral mass resection. After 50% resection, Oc-C1 AR ROM increased by 54.4% (p = 0.002), Oc LB ROM increased by 47.8% (p = 0.010), and Oc-C1 AR+E ROM increased by 65.8% (p < 0.001). Oc-C2 FE ROM increased by 7.2% (p = 0.016) after 50% resection; 75% and 100% lateral mass resection resulted in further increases in ROM. CONCLUSIONS: In this cadaveric biomechanical study, the authors found that unilateral C1 hemilaminectomy and 25% resection of the C1 lateral mass did not result in significant biomechanical instability at the occipitocervical junction, and 50% resection led to significant increases in Oc-C2 ROM. This is the first biomechanical study of lateral mass resection, and future studies can serve to validate these findings.

A generalized framework for determination of functional musculoskeletal joint coordinate systems.

Establishing anatomical coordinate systems (CS) from anatomical landmarks is sensitive to landmark selection. Vastly different results can be obtained amongst observers which can greatly affect the resulting joint kinematics. The aim of this study is to introduce an objective method for calculating functional CS definitions for bones in joints that observe three-cylindrical-joint kinematic chain decomposition methods and to apply the method on tibiofemoral joint specimens. This method is driven by low resistance joint motion during loading profiles and not from anatomical landmark selection. Two anatomical CS definitions were established from points collected by five observers, for twelve knees. The knees underwent passive flexion and internal/external rotation using the anatomical CSs. The kinematics from these profiles were used in linear least squares minimization of off-axis motions to redefine the tibia and femur origins, the femur flexion axis and the tibia internal rotation axis. Significant improvements in reproducibility of 7.4 mm (tibia origin, p < 0.001), 3.4 mm (femur origin, p < 0.001), and 2.9° (femur FE-axis, p < 0.001) between the two functional CSs compared to the two anatomical CSs were observed. Functional CSs led to significant decreases in off-axis motion during discrete passive flexion profiles. This new strategy for establishing functional CSs provides an objective approach that will reduce the effects of observer error in establishing CSs. Additionally, functional CSs allow for better interpretations of kinematic responses due to loading because effects of kinematic cross-talk is minimized.

Specimen specific imaging and joint mechanical testing data for next generation virtual knees.

Virtual knees, with specimen-specific anatomy and mechanics, require heterogeneous data collected on the same knee. Specimen-specific data such as the specimen geometry, physiological joint kinematics-kinetics and contact mechanics are necessary in the development of virtual knee specimens for clinical and scientific simulations. These data are also required to capture or evaluate the predictive capacity of the model to represent joint and tissue mechanical response. This document details the collection of magnetic resonance imaging data and, tibiofemoral joint and patellofemoral joint mechanical testing data. These data were acquired for a cohort of eight knee specimens representing different populations with varying gender, age and perceived health of the joint. These data were collected as part of the Open Knee(s) initiative. Imaging data when combined with joint mechanics data, may enable development and assessment of authentic specimen-specific finite element models of the knee. The data may also guide prospective studies for association of anatomical and biomechanical markers in a specimen-specific manner.

Phenotypic profiling of mGlu7 knockout mice reveals new implications for neurodevelopmental disorders.

Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu7 ), a G protein-coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu7 in the context of this specific disease class. Here, we show that the absence of mGlu7 in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu7 as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.

Reference data on in vitro anatomy and indentation response of tissue layers of musculoskeletal extremities.

The skin, fat, and muscle of the musculoskeletal system provide essential support and protection to the human body. The interaction between individual layers and their composite structure dictate the body's response during mechanical loading of extremity surfaces. Quantifying such interactions may improve surgical outcomes by enhancing surgical simulations with lifelike tissue characteristics. Recently, a comprehensive tissue thickness and anthropometric database of in vivo extremities was acquired using a load sensing instrumented ultrasound to enhance the fidelity of advancing surgical simulations. However detailed anatomy of tissue layers of musculoskeletal extremities was not captured. This study aims to supplement that database with an enhanced dataset of in vitro specimens that includes ultrasound imaging supported by motion tracking of the ultrasound probe and two additional full field imaging modalities (magnetic resonance and computed tomography). The additional imaging datasets can be used in conjunction with the ultrasound/force data for more comprehensive modeling of soft tissue mechanics. Researchers can also use the image modalities in isolation if anatomy of legs and arms is needed.

The fractal geometry of bronchial trees differs by strain in mice.

Fractal biological structures are pervasive throughout the plant and animal kingdoms, with the mammalian lung being a quintessential example. The lung airway and vascular trees are generated during embryogenesis from a small set of building codes similar to Turing mechanisms that create robust trees ideally suited to their functions. Whereas the blood flow pattern generated by these fractal trees has been shown to be genetically determined, the geometry of the trees has not. We explored a newly established repository providing high-resolution bronchial trees from the four most commonly studied laboratory mice (B6C3F1, BALB/c, C57BL/6 and CD-1). The data fit a fractal model well for all animals with the fractal dimensions ranging from 1.54 to 1.67, indicating that the conducting airway of mice can be considered a self-similar and space-filling structure. We determined that the fractal dimensions of these airway trees differed by strain but not sex, reinforcing the concept that airway branching patterns are encoded within the DNA. The observations also highlight that future study design and interpretations may need to consider differences in airway geometry between mouse strains.NEW & NOTEWORTHY Similar to larger mammals such as humans, the geometries of the bronchial tree in mice are fractal structures that have repeating patterns from the trachea to the terminal branches. The airway geometries of the four most commonly studied mice are different and need to be considered when comparing results that employ different mouse strains. This variability in mouse airway geometries should be incorporated into computer models exploring toxicology and aerosol deposition in mouse models.

Aerobic Exercise Effects on Quality of Life and Psychological Distress After an Implantable Cardioverter Defibrillator.

PURPOSE: The purpose of this study was to evaluate quality of life (QOL), psychological function, and self-efficacy outcomes in the Anti-Arrhythmic Effects of Exercise After an ICD Trial. METHODS: In the Anti-Arrhythmic Effects of Exercise After an ICD Trial, 160 patients (124 men and 36 women) who had an implantable cardioverter defibrillator for primary (43%) or secondary (57%) prevention were randomized to exercise (EX, n = 84) or usual care (UC, n = 76). The EX consisted of 8 wk of home walking 1 hr/d 5 d/wk, followed by 16 wk of maintenance home walking for 150 min/wk. Adherence was determined from exercise logs, ambulatory HR recordings, and phone calls. Assessments were conducted at baseline, 8, and 24 wk for QOL: Patient Concerns Assessment and Short Form-36; anxiety: State Trait Anxiety Inventory; depression: Physician Health Questionnaire-Depression; and self-efficacy: Self-Efficacy for Walking Scale. RESULTS: Participants averaged 55 ± 12 yr of age with ejection fraction = 40.6 ± 15.7%. The EX significantly decreased depression severity (EX: 1.33 ± 0.64; UC: 1.51 ± 0.86, P = .05) and improved self-efficacy (EX: 7.65 ± 1.97; UC: 6.85 ± 2.40, P = .05) at 8 wk. There were no significant effects at 24 wk. Adherent exercisers had significant improvements in QOL, psychological, and self-efficacy outcomes at 8 and 24 wk compared with those who were nonadherent. There were no implantable cardioverter defibrillator shocks associated with exercise. CONCLUSIONS: The EX conferred significant effects on depression and self-efficacy at 8 wk, without effects on QOL. Adherent exercisers experienced significant improvements in outcomes over those who were nonadherent or received UC.

Use of esophageal stents to relieve dysphagia during neoadjuvant therapy prior to esophageal resection: a systematic review.

Esophageal cancer stenting offers symptomatic relief for patients suffering from dysphagia. There are limited data to support their use to relieve dysphagia and improve nutrition during neoadjuvant therapy with some concern that they may negatively impact oncological outcomes. The aim of this systematic review was to quantify the impact of esophageal stents on outcomes prior to resection with curative intent. A literature search was performed using Embase, Medline, PubMed, PubMed Central, the Cochrane library for articles pertaining to esophageal stent use prior to or during neoadjuvant chemotherapy or chemoradiotherapy in patients planned for curative esophagectomy. Data extracted included basic demographics, clinical, nutritional and oncologic outcomes. A total of 9 studies involving 465 patients were included. Esophageal stent use resulted in a significant improvement in mean dysphagia scores in the immediate post stent period but failed to demonstrate any positive changes in weight, body mass index (BMI) or albumin. Only 33% of stented patients ultimately progressed to potential curative surgical resection and stents were associated with reduced R0 resection rates and lower overall survival. This systematic review shows that, although esophageal stenting is associated with improvements in dysphagia during neoadjuvant therapy, their effect on improving patient nutritional status is less clear and they may be associated with poorer long-term oncological outcomes. Stents should be used with caution in patients who are being considered for potentially curative resection of esophageal malignancies and other strategies of nutritional supplementation should be considered.

lapdMouse: associating lung anatomy with local particle deposition in mice.

To facilitate computational toxicology, we developed an approach for generating high-resolution lung-anatomy and particle-deposition mouse models. Major processing steps of our method include mouse preparation, serial block-face cryomicrotome imaging, and highly automated image analysis for generating three-dimensional (3D) mesh-based models and volume-based models of lung anatomy (airways, lobes, sublobes, and near-acini structures) that are linked to local particle-deposition measurements. Analysis resulted in 34 mouse models covering 4 different mouse strains (B6C3F1: 8, BALB/C: 11, C57Bl/6: 8, and CD-1: 7) as well as both sexes (16 male and 18 female) and different particle sizes [2 µm (n = 15), 1 µm (n = 16), and 0.5 µm (n = 3)]. On average, resulting mouse airway models had 1,616.9 ± 298.1 segments, a centerline length of 597.6 ± 59.8 mm, and 1,968.9 ± 296.3 outlet regions. In addition to 3D geometric lung models, matching detailed relative particle-deposition measurements are provided. All data sets are available online in the lapdMouse archive for download. The presented approach enables linking relative particle deposition to anatomical structures like airways. This will in turn improve the understanding of site-specific airflows and how they affect drug, environmental, or biological aerosol deposition.NEW & NOTEWORTHY Computer simulations of particle deposition in mouse lungs play an important role in computational toxicology. Until now, a limiting factor was the lack of high-resolution mouse lung models and measured local particle-deposition information, which are required for developing accurate modeling approaches (e.g., computational fluid dynamics). With the developed imaging and analysis approach, we address this issue and provide all of the raw and processed data in a publicly accessible repository.

Development of a novel in vitro cadaveric model for analysis of biomechanics and surgical treatment of Bertolotti syndrome.

BACKGROUND CONTEXT: Bertolotti syndrome (BS) is caused by pseudoarticulation between an aberrant L5 transverse process and the sacral ala, termed a lumbosacral transitional vertebra (LSTV). BS is thought to cause low back pain and is treated with resection or fusion, both of which have shown success. Acquiring cadavers with BS is challenging. Thus, we combined 3D printing, based on BS patient CT scans, with normal cadaveric spines to create a BS model. We then performed biomechanical testing to determine altered kinematics from LSTV with surgical interventions. Force sensing within the pseudojoint modeled nociception for different trajectories of motion and surgical conditions. PURPOSE: This study examines alterations in spinal biomechanics with LSTVs and with various surgical treatments for BS in order to learn more about pain and degeneration in this condition, in order to help optimize surgical decision-making. In addition, this study evaluates BS histology in order to better understand the pathology and to help define pain generators-if, indeed, they actually exist. STUDY DESIGN/SETTING: Model Development: A retrospective patient review of 25 patients was performed to determine the imaging criteria that defines the classical BS patient. Surgical tissue was extracted from four BS patients for 3D-printing material selection. Biomechanical Analysis. This was a prospective cadaveric biomechanical study of seven spines evaluating spinal motions, and loads, over various surgical conditions (intact, LSTV, and LSTV with various fusions). Additionally, forces at the LSTV joint were measured for the LSTV and LSTV with fusion condition. Histological Analysis: Histologic analysis was performed prospectively on the four surgical specimens from patients undergoing pseudoarthrectomy for BS at our institution to learn more about potential pain generators. PATIENT SAMPLE: The cadaveric portion of the study involved seven cadaveric spines. Four patients were prospectively recruited to have their surgical specimens assessed histologically and biomechanically for this study. Patients under the age of 18 were excluded. OUTCOME MEASURES: Physiological measures recorded in this study were broken down into histologic analysis, tissue biomechanical analysis, and joint biomechanical analysis. Histologic analysis included pathologist interpretation of Hematoxylin and Eosin staining, as well as S-100 staining. Tissue biomechanical analysis included stiffness measurements. Joint biomechanical analysis included range of motion, resultant torques, relative axis angles, and LSTV joint forces. METHODS: This study received funding from the American Academy of Neurology Medical Student Research Scholarship. Three authors hold intellectual property rights in the simVITRO robotic testing system. No other authors had relevant conflicts of interest for this study. CT images were segmented for a representative BS patient and cadaver spines. Customized cutting and drilling guides for LSTV attachment were created for individual cadavers. 3D-printed bone and cartilage structural properties were based on surgical specimen stiffness, and specimens underwent histologic analysis via Hematoxylin and Eosin, as well as S-100 staining. Joint biomechanical testing was performed on the robotic testing system for seven specimens. Force sensors detected forces in the LSTV joint. Kruskal-Wallis tests and Dunnett's tests were used for statistical analysis with significance bounded to p<.05. RESULTS: LSTV significantly reduces motion at the L5-S1 level, particularly in lateral bending and axial rotation. Meanwhile, the LSTV increases adjacent segment motion significantly at the L2-L3 level, whereas other levels have nonsignificant trends toward increased motion with LSTV alone. Fusion involving L4-S1 (L4-L5 and L5-S1) to treat adjacent level degeneration associated with an LSTV is associated with a significant increase in adjacent segment motion at all levels other than L5-S1 compared to LSTV alone. Fusion of L5-S1 alone with LSTV significantly increases L3-L4 adjacent segment motion compared to LSTV alone. Last, ipsilateral lateral bending with or without ipsilateral axial rotation produces the greatest force on the LSTV, and these forces are significantly reduced with L5-S1 fusion. CONCLUSIONS: BS significantly decreases L5-S1 mobility, and increases some adjacent segment motion, potentially causing patient activity restriction and discomfort. Ipsilateral lateral bending with or without ipsilateral axial rotation may cause the greatest discomfort overall in these patients, and fusion of the L5-S1 or L4-S1 levels may reduce pain associated with these motions. However, due to increased adjacent segment motion with fusions compared to LSTV alone, resection of the joint may be the better treatment option if the superior levels are not unstable preoperatively. CLINICAL SIGNIFICANCE: This study's results indicate that patients with BS have significantly altered spinal biomechanics and may develop pain due to increased loading forces at the LSTV joint with ipsilateral lateral bending and axial rotation. In addition, increased motion at superior levels when an LSTV is present may lead to degeneration over time. Based upon results of LSTV joint force testing, these patients' pain may be effectively treated surgically with LSTV resection or fusion involving the LSTV level if conservative management fails. Further studies are being pursued to evaluate the relationship between in vivo motion of BS patients, spinal and LSTV positioning, and pain generation to gain a better understanding of the exact source of pain in these patients. The methodologies utilized in this study can be extrapolated to recreate other spinal conditions that are poorly understood, and for which few native cadaveric specimens exist.

Robotically Simulated Pivot Shift That Represents the Clinical Exam.

A thorough understanding of anterior cruciate ligament (ACL) function and the effects of surgical interventions on knee biomechanics requires robust technologies and simulation paradigms that align with clinical insight. In vitro orthopedic biomechanical testing for the elucidation of ACL integrity doesn't have an established testing paradigm to simulate the clinical pivot shift exam on cadaveric specimens. The study aim was to develop a robotically simulated pivot shift that represents the clinical exam. An orthopedic surgeon performed a pivot shift on an instrumented ACL-deficient cadaver leg to capture 6 degree-of-freedom motion/loads. The same knee was mounted to the robot and the sensitivity of the motion/loading profiles quantified. Three loading profile candidates that generated positive pivot shifts on the instrumented knee were selected and applied to 7 ACL-intact/deficient specimens and resulted in the identification of a profile that was able to induce a positive pivot shift in all ACL-deficient specimens ( p < 0.001). The simulated shifts began at 22 ± 8° and ended at 33 ± 6° of flexion with the average magnitude of the shifts being 12.8 ± 3.2 mm in anterior tibial translation and 17.6 ± 4.3° in external tibial rotation. The establishment and replication of a robotically simulated clinical pivot shift across multiple specimens show the robustness of the loading profile to accommodate anatomical and experimental variability. Further evaluation and refinement should be undertaken to create a useful tool in evaluating ACL function and reconstruction techniques. Statement of clinical significance: Creation and successful demonstration of the simulated clinical pivot shift validates a profile for robotic musculoskeletal simulators to analyze ACL related clinical questions. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2601-2608, 2019.

A perpetual switching system in pulmonary capillaries.

Of the 300 billion capillaries in the human lung, a small fraction meet normal oxygen requirements at rest, with the remainder forming a large reserve. The maximum oxygen demands of the acute stress response require that the reserve capillaries are rapidly recruited. To remain primed for emergencies, the normal cardiac output must be parceled throughout the capillary bed to maintain low opening pressures. The flow-distributing system requires complex switching. Because the pulmonary microcirculation contains contractile machinery, one hypothesis posits an active switching system. The opposing hypothesis is based on passive switching that requires no regulation. Both hypotheses were tested ex vivo in canine lung lobes. The lobes were perfused first with autologous blood, and capillary switching patterns were recorded by videomicroscopy. Next, the vasculature of the lobes was saline flushed, fixed by glutaraldehyde perfusion, flushed again, and then reperfused with the original, unfixed blood. Flow patterns through the same capillaries were recorded again. The 16-min-long videos were divided into 4-s increments. Each capillary segment was recorded as being perfused if at least one red blood cell crossed the entire segment. Otherwise it was recorded as unperfused. These binary measurements were made manually for each segment during every 4 s throughout the 16-min recordings of the fresh and fixed capillaries (>60,000 measurements). Unexpectedly, the switching patterns did not change after fixation. We conclude that the pulmonary capillaries can remain primed for emergencies without requiring regulation: no detectors, no feedback loops, and no effectors-a rare system in biology. NEW & NOTEWORTHY The fluctuating flow patterns of red blood cells within the pulmonary capillary networks have been assumed to be actively controlled within the pulmonary microcirculation. Here we show that the capillary flow switching patterns in the same network are the same whether the lungs are fresh or fixed. This unexpected observation can be successfully explained by a new model of pulmonary capillary flow based on chaos theory and fractal mathematics.

Reference data on thickness and mechanics of tissue layers and anthropometry of musculoskeletal extremities.

Musculoskeletal extremities exhibit a multi-layer tissue structure that is composed of skin, fat, and muscle. Body composition and anthropometric measurements have been used to assess health status and build anatomically accurate biomechanical models of the limbs. However, comprehensive datasets inclusive of regional tissue anatomy and response under mechanical manipulation are missing. The goal of this study was to acquire and disseminate anatomical and mechanical data collected on extremities of the general population. An ultrasound system, instrumented with a load transducer, was used for in vivo characterization of skin, fat, and muscle thicknesses in the extremities of 100 subjects at unloaded (minimal force) and loaded (through indentation) states. For each subject, the unloaded and loaded state provided anatomic tissue layer measures and tissue indentation response for 48 and 8 regions, respectively. A publicly available web-based system has been used for data management and dissemination. This comprehensive database will provide the foundation for comparative studies in regional musculoskeletal composition and improve visual and haptic realism for computational models of the limbs.