Mesenchymal Stem Cell-Derived Extracellular Vesicles Decrease Lung Injury in Mice.

Human mesenchymal stem cell (MSC) extracellular vesicles (EV) can reduce the severity of bacterial pneumonia, but little is known about the mechanisms underlying their antimicrobial activity. In the current study, we found that bacterial clearance induced by MSC EV in Escherichia coli pneumonia in C57BL/6 mice was associated with high levels of leukotriene (LT) B4 in the injured alveolus. More importantly, the antimicrobial effect of MSC EV was abrogated by cotreatment with a LTB4 BLT1 antagonist. To determine the role of MSC EV on LT metabolism, we measured the effect of MSC EV on a known ATP-binding cassette transporter, multidrug resistance-associated protein 1 (MRP1), and found that MSC EV suppressed MRP1 mRNA, protein, and pump function in LPS-stimulated Raw264.7 cells in vitro. The synthesis of LTB4 and LTC4 from LTA4 are competitive, and MRP1 is the efflux pump for LTC4 Inhibition of MRP1 will increase LTB4 production. In addition, administration of a nonspecific MRP1 inhibitor (MK-571) reduced LTC4 and subsequently increased LTB4 levels in C57BL/6 mice with acute lung injury, increasing overall antimicrobial activity. We previously found that the biological effects of MSC EV were through the transfer of its content, such as mRNA, microRNA, and proteins, to target cells. In the current study, miR-145 knockdown abolished the effect of MSC EV on the inhibition of MRP1 in vitro and the antimicrobial effect in vivo. In summary, MSC EV suppressed MRP1 activity through transfer of miR-145, thereby resulting in enhanced LTB4 production and antimicrobial activity through LTB4/BLT1 signaling.

Risk factors of posthepatectomy liver failure for perihilar cholangiocarcinoma: Risk score and significance of future liver remnant volume-to-body weight ratio.

BACKGROUND: Surgery for perihilar cholangiocarcinoma (PHCC) is associated with high morbidity. This study aimed to investigate the clinical value of the future liver remnant volume-to-body weight (FLRV/BW) and propose a risk score for predicting the risk of patients with PHCC developing posthepatectomy liver failure (PHLF). METHODS: This study included 348 patients who underwent major hepatectomy with bile duct resection for PHCC during 2008-2015 at a single center in Korea and they were retrospectively analyzed. RESULTS: Clinically relevant PHLF was noted in 40 patients (11.4%). The area under the curve (AUC) for FLRV/BW was not significantly different from that for FLRV/total liver volume (P = .803) or indocyanine green clearance of the future liver remnant (P = .629) in terms of predicting PHLF. On multivariate analysis, predictors of PHLF (P < .05) were male sex, albumin less than 3.5 g/dL, preoperative cholangitis, portal vein resection, FLRV/BW less than 0.5%, and FLRV/BW 0.5% to 0.75%. These variables were included in the risk score that showed good discrimination (AUC, 0.853; 95% CI, 0.802-0.904). It will help rank patients into three risk subgroups with a predicted liver failure incidence of 4.75%, 18.73%, and 51.58%, respectively. CONCLUSIONS: FLRV/BW is a comparable risk prediction factor of PHLF and the proposed risk score can help to predict the risk of planned surgery in PHCC.

Comparison of the laryngeal mask airway supreme and the i-gel in paralysed elderly patients: A randomised controlled trial.

BACKGROUND: The laryngeal mask airway supreme (LMA-S) and i-gel are both popular second-generation supraglottic airway devices that have been widely studied in surgical patients, but their differences in clinical performance in the elderly are not clear. OBJECTIVE: We compared the efficacy and safety of the LMA-S and i-gel in anaesthetised and paralysed elderly patients. DESIGN: A randomised study. SETTING: Single-centre trial, study period January 2014 from to October 2016. PATIENTS: One hundred and six elderly patients who underwent urological or orthopaedic surgery with an expected duration less than 2 h. INTERVENTION: Patients were allocated to either the LMA-S (n = 53) or i-gel (n = 53) group. All insertions were performed in a standardised manner according to the manufacturers' instructions. MAIN OUTCOME MEASURES: Our primary endpoint was the rate of successful insertion at the first attempt. The adequacy of positive pressure ventilation and airway sealing, fibreoptic laryngoscopy grades and stability of airway maintenance during anaesthesia were also assessed. RESULTS: Although the rate of successful insertion at the first attempt was similar between the two groups (94.3 vs. 82.7%, P = 0.072), more patients required device manipulation during insertion with the LMA-S than the i-gel (42.3 vs. 18.9%, P = 0.011). Good fibreoptic laryngoscopy grades were significantly more common with the i-gel than the LMA-S (79.3 vs. 55.8%, P = 0.042), and peak inspiratory pressures were lower in the i-gel group both immediately after insertion and at the end of surgery. Leak pressures were significantly higher in the i-gel group than the LMA-S group, both immediately after insertion and at the end of surgery (25.8 vs. 23.0, P = 0.036; and 28.1 vs. 23.7, P < 0.001, respectively). CONCLUSION: Both the LMA-S and i-gel were used successfully and safely in elderly patients. However, the i-gel demonstrated better airway sealing than the LMA-S at insertion and during maintenance of anaesthesia. TRIAL REGISTRATION: NCT02026791 at clinicaltrial.gov.

Continuous treatment with lenalidomide and low-dose dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma in Asia: subanalysis of the FIRST trial.

The phase 3 FIRST (Frontline Investigation of REVLIMID + Dexamethasone Versus Standard Thalidomide) trial demonstrated that lenalidomide plus low-dose dexamethasone (Rd) until disease progression (Rd continuous) is an effective treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Given genetic differences between Asian and Western populations, this subanalysis of the FIRST trial examined the safety and efficacy of Rd (given continuously or for 18 cycles [Rd18]) and MPT (melphalan, prednisone, thalidomide) in 114 Asian patients from Mainland China, South Korea and Taiwan. Efficacy and safety with Rd continuous in Asian patients were consistent with those in the overall study population. The overall response rates were 77·8% for Rd continuous, 57·5% for MPT and 65·8% for Rd18. The risk of progression or death was reduced by 39% with Rd continuous versus MPT and by 35% with Rd continuous versus Rd18. Rd continuous improved the 3-year survival rate compared with MPT (70·2% vs. 56·4%) and Rd18 (58·1%). Common grade 3/4 adverse events in the Rd continuous and MPT arms were neutropenia (25·0% vs. 43·6%), infection (19·4% vs. 28·2%) and anaemia (19·4% vs. 15·4%), respectively. Thromboembolic event rates were low, and no second primary malignancies were observed. Rd continuous is safe and effective in transplant-ineligible Asian patients with NDMM.

Effects of volatile anesthetic choice on hospital length-of-stay: a retrospective study and a prospective trial.

BACKGROUND: Volatile anesthetic prices differ substantially. But differences in drug-acquisition cost would be inconsequential if hospitalization were prolonged by more soluble anesthetics. The authors tested the hypothesis that the duration of hospitalization is prolonged with isoflurane anesthesia. METHODS: Initially, the authors queried their electronic records and used propensity matching to generate homogeneous sets of adults having inpatient noncardiac surgery who were given desflurane, sevoflurane, and isoflurane. The authors then conducted a prospective alternating intervention trial in which adults (mostly having colorectal surgery) were assigned to isoflurane or sevoflurane, based on protocol. RESULTS: In the retrospective analysis, 2,898 matched triplets were identified among 43,352 adults, each containing one patient receiving isoflurane, desflurane, and sevoflurane, respectively. The adjusted geometric mean (95% CI) hospital length-of-stay for the isoflurane cases was 2.85 days (2.78-2.93); this was longer than that observed for both desflurane (2.64 [2.57-2.72]; P<0.001) and sevoflurane (2.55 [2.48-2.62]; P<0.001). In the prospective trial (N=1,584 operations), no difference was found; the adjusted ratio of means (95% CI) of hospital length-of-stay in patients receiving isoflurane versus sevoflurane was 0.98 (0.88-1.10), P=0.77, with adjusted geometric means (95% CI) estimated at 4.1 (3.8-4.4) and 4.2 days (3.8-4.5), respectively. CONCLUSIONS: Results of the propensity-matched retrospective analysis suggested that avoiding isoflurane significantly reduced the duration of hospitalization. In contrast, length-of-stay was comparable in our prospective trial. Volatile anesthetic choice should not be based on concerns about the duration of hospitalization. These studies illustrate the importance of following even the best retrospective analysis with a prospective trial.

Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery.

BACKGROUND: The authors tested the primary hypothesis that perioperative IV lidocaine administration during spine surgery (and in the postanesthesia care unit for no more than 8 h) decreases pain and/or opioid requirements in the initial 48 postoperative hours. Secondary outcomes included major complications, postoperative nausea and vomiting, duration of hospitalization, and quality of life. METHODS: One hundred sixteen adults having complex spine surgery were randomly assigned to perioperative IV lidocaine (2 mg·kg·h) or placebo during surgery and in the postanesthesia care unit. Pain was evaluated with a verbal response scale. Quality of life at 1 and 3 months was assessed using the Acute Short-form (SF) 12 health survey. The authors initially evaluated multivariable bidirectional noninferiority on both outcomes; superiority on either outcome was then evaluated only if noninferiority was established. RESULTS: Lidocaine was significantly superior to placebo on mean verbal response scale pain scores (P < 0.001; adjusted mean [95% CI] of 4.4 [4.2-4.7] and 5.3 [5.0-5.5] points, respectively) and significantly noninferior on mean morphine equivalent dosage (P = 0.011; 55 [36-84] and 74 [49-111] mg, respectively). Postoperative nausea and vomiting and the duration of hospitalization did not differ significantly. Patients given lidocaine had slightly fewer 30-day complications than patients given placebo (odds ratio [95% CI] of 0.91 [0.84-1.00]; P = 0.049). Patients given lidocaine had significantly greater SF-12 physical composite scores than placebo at 1 (38 [31-47] vs. 33 [27-42]; P = 0.002) and 3 (39 [31-49] vs. 34 [28-44]; P = 0.04) months, postoperatively. CONCLUSION: IV lidocaine significantly improves postoperative pain after complex spine surgery.

Cerebrospinal fluid pressures resulting from experimental traumatic spinal cord injuries in a pig model.

Despite considerable effort over the last four decades, research has failed to translate into consistently effective treatment options for spinal cord injury (SCI). This is partly attributed to differences between the injury response of humans and rodent models. Some of this difference could be because the cerebrospinal fluid (CSF) layer of the human spine is relatively large, while that of the rodents is extremely thin. We sought to characterize the fluid impulse induced in the CSF by experimental SCIs of moderate and high human-like severity, and to compare this with previous studies in which fluid impulse has been associated with neural tissue injury. We used a new in vivo pig model (n = 6 per injury group, mean age 124.5 days, 20.9 kg) incorporating four miniature pressure transducers that were implanted in pairs in the subarachnoid space, cranial, and caudal to the injury at 30 mm and 100 mm. Tissue sparing was assessed with Eriochrome Cyanine and Neutral Red staining. The median peak pressures near the injury were 522.5 and 868.8 mmHg (range 96.7-1430.0) and far from the injury were 7.6 and 36.3 mmHg (range 3.8-83.7), for the moderate and high injury severities, respectively. Pressure impulse (mmHg.ms), apparent wave speed, and apparent attenuation factor were also evaluated. The data indicates that the fluid pressure wave may be sufficient to affect the severity and extent of primary tissue damage close to the injury site. However, the CSF pressure was close to normal physiologic values at 100 mm from the injury. The high injury severity animals had less tissue sparing than the moderate injury severity animals; this difference was statistically significant only within 1.6 mm of the epicenter. These results indicate that future research seeking to elucidate the mechanical origins of primary tissue damage in SCI should consider the effects of CSF. This pig model provides advantages for basic and preclinical SCI research due to its similarities to human scale, including the existence of a human-like CSF fluid layer.

A Nodal Immersed Finite Element-Finite Difference Method.

The immersed finite element-finite difference (IFED) method is a computational approach to modeling interactions between a fluid and an immersed structure. The IFED method uses a finite element (FE) method to approximate the stresses, forces, and structural deformations on a structural mesh and a finite difference (FD) method to approximate the momentum and enforce incompressibility of the entire fluid-structure system on a Cartesian grid. The fundamental approach used by this method follows the immersed boundary framework for modeling fluid-structure interaction (FSI), in which a force spreading operator prolongs structural forces to a Cartesian grid, and a velocity interpolation operator restricts a velocity field defined on that grid back onto the structural mesh. With an FE structural mechanics framework, force spreading first requires that the force itself be projected onto the finite element space. Similarly, velocity interpolation requires projecting velocity data onto the FE basis functions. Consequently, evaluating either coupling operator requires solving a matrix equation at every time step. Mass lumping, in which the projection matrices are replaced by diagonal approximations, has the potential to accelerate this method considerably. This paper provides both numerical and computational analyses of the effects of this replacement for evaluating the force projection and for the IFED coupling operators. Constructing the coupling operators also requires determining the locations on the structure mesh where the forces and velocities are sampled. Here we show that sampling the forces and velocities at the nodes of the structural mesh is equivalent to using lumped mass matrices in the IFED coupling operators. A key theoretical result of our analysis is that if both of these approaches are used together, the IFED method permits the use of lumped mass matrices derived from nodal quadrature rules for any standard interpolatory element. This is different from standard FE methods, which require specialized treatments to accommodate mass lumping with higher-order shape functions. Our theoretical results are confirmed by numerical benchmarks, including standard solid mechanics tests and examination of a dynamic model of a bioprosthetic heart valve.

Patient-Specific Immersed Finite Element-Difference Model of Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) first received FDA approval for high-risk surgical patients in 2011 and has been approved for low-risk surgical patients since 2019. It is now the most common type of aortic valve replacement, and its use continues to accelerate. Computer modeling and simulation (CM&S) is a tool to aid in TAVR device design, regulatory approval, and indication in patient-specific care. This study introduces a computational fluid-structure interaction (FSI) model of TAVR with Medtronic's CoreValve Evolut R device using the immersed finite element-difference (IFED) method. We perform dynamic simulations of crimping and deployment of the Evolut R, as well as device behavior across the cardiac cycle in a patient-specific aortic root anatomy reconstructed from computed tomography (CT) image data. These IFED simulations, which incorporate biomechanics models fit to experimental tensile test data, automatically capture the contact within the device and between the self-expanding stent and native anatomy. Further, we apply realistic driving and loading conditions based on clinical measurements of human ventricular and aortic pressures and flow rates to demonstrate that our Evolut R model supports a physiological diastolic pressure load and provides informative clinical performance predictions.

Rapidly developed heterotopic ossification: a rare complication after trauma.

Heterotopic ossification (HO) is a condition where aberrant bone grows in tissues. This case study presents a rare complication of trauma and laparotomies, where the rapid and extensive occurrence of HO has delayed abdominal incision closure resulting in multiple surgeries and prolonged recovery. A 44-year-old man was retrieved after a truck accident resulting in multi-organ injuries. He required damage control trauma laparotomy followed by several relooks and multiple orthopaedic procedures. Despite several attempts, approximation of the laparostomy wound was not possible due to abdominal rigidity. Computed tomography scans done 20 days after injury demonstrated advanced HO over the wound edge. Early development of HO may explain why the abdominal incision was difficult to close and highlights the importance of being aware of HO as an early complication after trauma and midline laparotomy.

On the Lagrangian-Eulerian Coupling in the Immersed Finite Element/Difference Method.

The immersed boundary (IB) method is a non-body conforming approach to fluid-structure interaction (FSI) that uses an Eulerian description of the momentum, viscosity, and incompressibility of a coupled fluid-structure system and a Lagrangian description of the deformations, stresses, and resultant forces of the immersed structure. Integral transforms with Dirac delta function kernels couple the Eulerian and Lagrangian variables, and in practice, discretizations of these integral transforms use regularized delta function kernels. Many different kernel functions have been proposed, but prior numerical work investigating the impact of the choice of kernel function on the accuracy of the methodology has often been limited to simplified test cases or Stokes flow conditions that may not reflect the method's performance in applications, particularly at intermediate-to-high Reynolds numbers, or under different loading conditions. This work systematically studies the effect of the choice of regularized delta function in several fluid-structure interaction benchmark tests using the immersed finite element/difference (IFED) method, which is an extension of the IB method that uses a finite element structural discretization combined with a Cartesian grid finite difference method for the incompressible Navier-Stokes equations. Whereas the conventional IB method spreads forces from the nodes of the structural mesh and interpolates velocities to those nodes, the IFED formulation evaluates the regularized delta function on a collection of interaction points that can be chosen to be denser than the nodes of the Lagrangian mesh. This opens the possibility of using structural discretizations with wide node spacings that would produce gaps in the Eulerian force in nodally coupled schemes (e.g., if the node spacing is comparable to or broader than the support of the regularized delta functions). Earlier work with this methodology suggested that such coarse structural meshes can yield improved accuracy for shear-dominated cases and, further, found that accuracy improves when the structural mesh spacing is increased. However, these results were limited to simple test cases that did not include substantial pressure loading on the structure. This study investigates the effect of varying the relative mesh widths of the Lagrangian and Eulerian discretizations in a broader range of tests. Our results indicate that kernels satisfying a commonly imposed even-odd condition require higher resolution to achieve similar accuracy as kernels that do not satisfy this condition. We also find that narrower kernels are more robust, in the sense that they yield results that are less sensitive to relative changes in the Eulerian and Lagrangian mesh spacings, and that structural meshes that are substantially coarser than the Cartesian grid can yield high accuracy for shear-dominated cases but not for cases with large normal forces. We verify our results in a large-scale FSI model of a bovine pericardial bioprosthetic heart valve in a pulse duplicator.

Intra-articular pressure characteristics of the knee joint: An exploratory study.

Inflammation-predominant osteoarthritis is an important clinical type of osteoarthritis, with synovitis suggested as its distinct pathophysiology. We investigated whether the synovium's mechanical properties in knees differed by osteoarthritis and other clinical parameters through retrospectively analyzing intra-articular pressure-volume characteristics. We analyzed 60 knees that were administered intra-articular corticosteroids while undergoing pressure monitoring. McMurray's test, pain complaints at end-range knee flexion, Kellgren-Lawrence classification from standing anteroposterior radiographs, and suprapatellar effusion from ultrasound constituted clinical parameters. Pressure-volume profiles-phasic changes in pressure by volume infusion, the volume of Phase 1-the potential volume of the synovial space, the pressure at 45 ml infusion-intra-articular pressure at a standardized volume, and the slope of Phase 2-synovial stiffness were compared with clinical parameters. All graphs were biphasic. Knees with suprapatellar effusion or radiologically definite osteoarthritis (Kellgren-Lawrence grade ≥2), had a lower Phase 1 volume. Knees with definite radiographic osteoarthritis also showed higher pressures at 45 ml and Phase 2 slopes (171.11 ± 94.35 mmHg and 5.08 ± 3.07 mmHg/ml, respectively) than those without (101.88 ± 58.12 mmHg and 2.84 ± 1.27 mmHg/ml, respectively). The Phase 2 slope was higher for knees with positive provocative tests than in those with negative provocative tests, although not statistically significant. The synovium stretched earlier in knees with effusion or radiologically definite osteoarthritis. Intra-articular pressure and synovial stiffness were significantly higher in patients with radiologically definite osteoarthritis. The synovium's mechanical characteristics are altered by osteoarthritis of the knee joint. Intra-articular pressure characteristics could be utilized for synovial evaluation clinically.

Incidence of spinal cord ischemia according to the patency of reimplanted segmental arteries during thoracoabdominal aortic replacement.

BACKGROUND: This study aimed to investigate the impact of segmental artery reimplantation and its patency on spinal cord ischemia (SCI) in thoracoabdominal aorta replacement. METHODS: For 193 patients who underwent early postoperative computed tomographic (CT) angiography after thoracoabdominal aorta replacement, the technique of segmental artery reimplantation, their patency, and postoperative SCI were retrospectively investigated. RESULTS: The early patency rate of reimplanted segmental artery was 83.3% (210 of 252), as 13 were taken down intraoperatively and 42 were not visualized in the postoperative CT angiography. The patency rate differed according to the reimplantation technique: 93.6% (131/140) for en bloc patch, 95.6% (43/45) for small individual patch, and 53.7% (36/67) for graft interposition. SCI occurred in 13 (6.3%) patients, 4 of whom (2.0%) remained paraplegic permanently. SCI was significantly more frequent (P=0.044) in the patients in whom segmental artery reimplantation was not successful (take-down or occlusion, 6/37=16.2%) than in those who had all segmental arteries sacrificed intentionally (2/64=3.1%) and those who showed patency of all reimplanted segmental arteries (5/92=5.4%). Especially, there was no permanent paraplegia in the last group. Failure of intended segmental artery reimplantation was a significant risk factor of postoperative SCI in logistic regression analysis (P=0.012; odds ratio 4.65, 95% confidence interval 1.41-15.36). CONCLUSIONS: During thoracoabdominal aorta replacement, attention should be paid to the segmental artery reimplantation technique, which affects the risk of occlusion or intraoperative take-down and thereby may have impact on postoperative SCI.

Bioprosthetic aortic valve diameter and thickness are directly related to leaflet fluttering: Results from a combined experimental and computational modeling study.

OBJECTIVE: Bioprosthetic heart valves (BHVs) are commonly used in surgical and percutaneous valve replacement. The durability of percutaneous valve replacement is unknown, but surgical valves have been shown to require reintervention after 10 to 15 years. Further, smaller-diameter surgical BHVs generally experience higher rates of prosthesis-patient mismatch, which leads to higher rates of failure. Bioprosthetic aortic valves can flutter in systole, and fluttering is associated with fatigue and failure in flexible structures. The determinants of flutter in BHVs have not been well characterized, despite their potential to influence durability. METHODS: We use an experimental pulse duplicator and a computational fluid-structure interaction model of this system to study the role of device geometry on BHV dynamics. The experimental system mimics physiological conditions, and the computational model enables precise control of leaflet biomechanics and flow conditions to isolate the effects of variations in BHV geometry on leaflet dynamics. RESULTS: Both experimental and computational models demonstrate that smaller-diameter BHVs yield markedly higher leaflet fluttering frequencies across a range of conditions. The computational model also predicts that fluttering frequency is directly related to leaflet thickness. A scaling model is introduced that rationalizes these findings. CONCLUSIONS: We systematically characterize the influence of BHV diameter and leaflet thickness on fluttering dynamics. Although this study does not determine how flutter influences device durability, increased flutter in smaller-diameter BHVs may explain how prosthesis-patient mismatch could induce BHV leaflet fatigue and failure. Ultimately, understanding the effects of device geometry on leaflet kinematics may lead to more durable valve replacements.

Comparing clinical outcomes between rotator cuff repairs, SLAP repairs, and combined repairs.

BACKGROUND: Superior labrum lesion from anterior to posterior (SLAP) often presents together with other shoulder pathologies such as rotator cuff tear (RCT), but it is uncertain if repairing both SLAP and RCT has superior clinical outcomes over isolated repairs of SLAP and RCT. MATERIALS AND METHODS: This was a retrospective cohort study with prospectively collected data, reviewing 157 patients who underwent arthroscopic repair of either RCT, SLAP (type II lesion), or both. Before surgery and after 6 weeks, 12 weeks, and 24 weeks, shoulder objective range of motion and strength were measured, patient-reported function and pain was assessed by the modified L'Insalata questionnaire with a Likert scale, and complications after each repair were examined. RESULTS: At 24 weeks after surgery, the combined group (n = 22) and SLAP group (n = 47) had significantly higher forward flexion (165° ± 4° and 167° ± 4° vs. 154° ± 3°, P = .01 and P = .01), external rotation strength (82 ± 6 N, 81 ± 6 N vs. 61 ± 3 N, P = .01 and P = .01), and abduction strength (94 ± 14 N, 78 ± 8 N vs. 53 ± 3 N, P = .001 and P = .02) compared with the rotator cuff tear repair (RCR) group (n = 88). The combined group also had stronger internal rotation than the RCR group (107 ± 12 N vs. 72 ± 4 N, P = .02). Function and pain improved from "severe-moderate" to "moderate-mild" in all groups after surgery. CONCLUSION: Repairing RCT and SLAP tears together results in significant clinical benefits compared to repairing just RCT and analogous results against SLAP-only repair.

Fluid-Structure Interaction Models of Bioprosthetic Heart Valve Dynamics in an Experimental Pulse Duplicator.

Computer modeling and simulation is a powerful tool for assessing the performance of medical devices such as bioprosthetic heart valves (BHVs) that promises to accelerate device design and regulation. This study describes work to develop dynamic computer models of BHVs in the aortic test section of an experimental pulse-duplicator platform that is used in academia, industry, and regulatory agencies to assess BHV performance. These computational models are based on a hyperelastic finite element extension of the immersed boundary method for fluid-structure interaction (FSI). We focus on porcine tissue and bovine pericardial BHVs, which are commonly used in surgical valve replacement. We compare our numerical simulations to experimental data from two similar pulse duplicators, including a commercial ViVitro system and a custom platform related to the ViVitro pulse duplicator. Excellent agreement is demonstrated between the computational and experimental results for bulk flow rates, pressures, valve open areas, and the timing of valve opening and closure in conditions commonly used to assess BHV performance. In addition, reasonable agreement is demonstrated for quantitative measures of leaflet kinematics under these same conditions. This work represents a step towards the experimental validation of this FSI modeling platform for evaluating BHVs.

Cytotoxicity and biomechanics of suture anchors used in labral repairs.

BACKGROUND: Biodegradable suture anchors are associated with higher redislocation rates. This study examined whether the biocompatibility and/or biomechanical properties of suture anchors contribute to the increase in complications. METHODS: Human glenohumeral capsule cells were cultured with 4 types of suture anchors, Opus LabraFix (titanium alloy; ArthroCare, Austin, TX, USA), PushLock (poly-ether-ether-ketone; Arthrex, Naples, FL, USA), BioKnotless (poly-l-lactic acid; DePuy Mitek, Warsaw, IN, USA), and Suretac II (polyglycolic acid; Smith & Nephew, London, UK), to measure cell viability and pH. Four groups of 6 ovine shoulders were used to repair the labrum, which was completely detached from the glenoid rim anteroinferiorly and reattached with 2 suture anchors and subject to failure load testing. RESULTS: In cell culture, BioKnotless at 48 and 72 hours (85.2% ± 2.1% and 84.5% ± 3.6%) and Suretac II groups (33.9% ± 3.1% and 42.8% ± 6.4%) had fewer viable cells compared with control (P = .048). The pH of Suretac II was lower than control (7.51 to 7.65) at 24 hours (7.31 ± 0.08, P = .049), 48 hours (7.25 ± 0.02, P = .046), and 72 hours (7.29 ± 0.04, P = .04). During mechanical testing, 83% of repairs failed by the capsule tearing. Among the anchors, the BioKnotless repair group had a significantly lower failure load (37 ± 5 N) compared with the PushLock (61 ± 7 N), Opus (60 ± 6 N), and Suretac II (57 ± 7 N) groups (P = .038). CONCLUSION: BioKnotless and Suretac II anchors are cytotoxic. The BioKnotless biodegradable anchor has significantly lower failure load. Absorbable suture anchors may cause higher redislocation of arthroscopic Bankart repair.

Endogenous TrkB ligands suppress functional mechanosensory plasticity in the deafferented spinal cord.

Dorsal root injury (DRI) disrupts the flow of sensory information to the spinal cord. Although primary afferents do not regenerate to their original targets, spontaneous recovery can, by unknown mechanisms, occur after DRI. Here, we show that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor or neurotrophin-4, are upregulated in the spinal gray matter after DRI. Because endogenous BDNF and NT-3 have well established roles in synaptic and axonal plasticity, we hypothesized that they contributed to spontaneous recovery after DRI. We first developed a model of DRI-induced mechanosensory dysfunction: rat C7/8 DRI produced a deficit in low-threshold cutaneous mechanosensation that spontaneously improved within 10 d but did not recover completely. To determine the effects of endogenous BDNF and NT-3, we administered TrkB-Fc or TrkC-Fc fusion proteins throughout the recovery period. To our surprise, TrkB-Fc stimulated complete recovery of mechanosensation by 6 d after DRI. It also stimulated mechanosensory axon sprouting but prevented deafferentation-induced serotonergic sprouting. TrkC-Fc had no effect on low-threshold mechanosensory behavior or axonal plasticity. There was no mechanosensory improvement with single-bolus TrkB-Fc infusions at 10 d after DRI (despite significantly reducing rhizotomy-induced cold pain), indicating that neuromodulatory effects of BDNF did not underlie mechanosensory recovery. Continuous infusion of the pan-neurotrophin antagonist K252a also stimulated behavioral and anatomical plasticity, indicating that these effects of TrkB-Fc treatment occurred independent of signaling by other neurotrophins. These results illustrate a novel, plasticity-suppressing effect of endogenous TrkB ligands on mechanosensation and mechanosensory primary afferent axons after spinal deafferentation.

Drug-induced and psychogenic resting suprahyoid neck and tongue tremors.

We describe three patients who presented with 4 to 5 Hz tremors of the suprahyoid region of the neck. Two developed their tremors in association with levosulpiride treatment. When they opened their mouths, the neck tremors disappeared; no tongue tremors were observed. However, a videofluoroscopic examination showed the presence of tongue tremors at rest. The remaining patient had a psychogenic tremor.