Pulmonary Embolism and Amniotic Fluid Embolism.

Venous thromboembolism (VTE) as well as other embolic events including amniotic fluid embolism (AFE) remain a leading cause of maternal death in the United States and worldwide. The pregnant patient is at a higher risk of developing VTE including pulmonary embolism. In contrast, AFE is a rare, but catastrophic event that remains incompletely understood. Here the authors review the cause of VTE in pregnancy and look at contemporary and evidence-based practices for the evaluation, diagnosis, and management in pregnancy. Then the cause and diagnostic difficulty of AFE as well as what is known regarding the pathogenesis are reviewed.

Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke.

Implanted vagus nerve stimulation (VNS) delivered concurrently with upper limb rehabilitation has been shown to improve arm function after stroke. Transcutaneous auricular VNS (taVNS) offers a non-invasive alternative to implanted VNS and may provide similar therapeutic benefit. There is much discussion about the optimal approach for combining VNS and physical therapy, as such we sought to determine whether taVNS administered during robotic training, specifically delivered during the premotor planning stage for arm extension movements, would confer additional motor improvement in patients with chronic stroke. Thirty-six patients with chronic, moderate-severe upper limb hemiparesis (>6 months; mean Upper Extremity Fugl-Meyer score = 25 ± 2, range 13-48), were randomized to receive 9 sessions (1 h in length, 3x/week for 3 weeks) of active (N = 18) or sham (N = 18) taVNS (500 ms bursts, frequency 30 Hz, pulse width 0.3 ms, max intensity 5 mA, ∼250 stimulated movements per session) delivered during robotic training. taVNS was triggered by the onset of a visual cue prior to center-out arm extension movements. Clinical assessments and surface electromyography (sEMG) measures of the biceps and triceps brachii were collected during separate test sessions. Significant motor improvements were measured for both the active and sham taVNS groups, and these improvements were robust at 3 month follow-up. Compared to the sham group, the active taVNS group showed a significant reduction in spasticity of the wrist and hand at discharge (Modified Tardieu Scale; taVNS = -8.94% vs. sham = + 2.97%, p < 0.05). The EMG results also demonstrated significantly increased variance for the bicep peak sEMG amplitude during extension for the active taVNS group compared to the sham group at discharge (active = 26.29% MVC ± 3.89, sham = 10.63% MVC ± 3.10, mean absolute change admission to discharge, p < 0.01), and at 3-month follow-up, the bicep peak sEMG amplitude was significantly reduced in the active taVNS group (P < 0.05). Thus, robot training improved the motor capacity of both groups, and taVNS, decreased spasticity. taVNS administered during premotor planning of movement may play a role in improving coordinated activation of the agonist-antagonist upper arm muscle groups by mitigating spasticity and increasing motor control following stroke. Clinical Trial Registration: www.ClinicalTrials.gov, identifier (NCT03592745).

LHX2 Mediates the FGF-to-SHH Regulatory Loop during Limb Development.

During limb development, fibroblast growth factors (Fgfs) govern proximal⁻distal outgrowth and patterning. FGFs also synchronize developmental patterning between the proximal⁻distal and anterior⁻posterior axes by maintaining Sonic hedgehog (Shh) expression in cells of the zone of polarizing activity (ZPA) in the distal posterior mesoderm. Shh, in turn, maintains Fgfs in the apical ectodermal ridge (AER) that caps the distal tip of the limb bud. Crosstalk between Fgf and Shh signaling is critical for patterned limb development, but the mechanisms underlying this feedback loop are not well-characterized. Implantation of Fgf beads in the proximal posterior limb bud can maintain SHH expression in the former ZPA domain (evident 3 h after application), while prolonged exposure (24 h) can induce SHH outside of this domain. Although temporally and spatially disparate, comparative analysis of transcriptome data from these different populations accentuated genes involved in SHH regulation. Comparative analysis identified 25 candidates common to both treatments, with eight linked to SHH expression or function. Furthermore, we demonstrated that LHX2, a LIM Homeodomain transcription factor, is an intermediate in the FGF-mediated regulation of SHH. Our data suggest that LHX2 acts as a competency factor maintaining distal posterior SHH expression subjacent to the AER.

Anterolateral Knee Extra-articular Stabilizers: A Robotic Sectioning Study of the Anterolateral Ligament and Distal Iliotibial Band Kaplan Fibers.

BACKGROUND: The individual kinematic roles of the anterolateral ligament (ALL) and the distal iliotibial band Kaplan fibers in the setting of anterior cruciate ligament (ACL) deficiency require further clarification. This will improve understanding of their potential contribution to residual anterolateral rotational laxity after ACL reconstruction and may influence selection of an anterolateral extra-articular reconstruction technique, which is currently a matter of debate. Hypothesis/Purpose: To compare the role of the ALL and the Kaplan fibers in stabilizing the knee against tibial internal rotation, anterior tibial translation, and the pivot shift in ACL-deficient knees. We hypothesized that the Kaplan fibers would provide greater tibial internal rotation restraint than the ALL in ACL-deficient knees and that both structures would provide restraint against internal rotation during a simulated pivot-shift test. STUDY DESIGN: Controlled laboratory study. METHODS: Ten paired fresh-frozen cadaveric knees (n = 20) were used to investigate the effect of sectioning the ALL and the Kaplan fibers in ACL-deficient knees with a 6 degrees of freedom robotic testing system. After ACL sectioning, sectioning was randomly performed for the ALL and the Kaplan fibers. An established robotic testing protocol was utilized to assess knee kinematics when the specimens were subjected to a 5-N·m internal rotation torque (0°-90° at 15° increments), a simulated pivot shift with 10-N·m valgus and 5-N·m internal rotation torque (15° and 30°), and an 88-N anterior tibial load (30° and 90°). RESULTS: Sectioning of the ACL led to significantly increased tibial internal rotation (from 0° to 90°) and anterior tibial translation (30° and 90°) as compared with the intact state. Significantly increased internal rotation occurred with further sectioning of the ALL (15°-90°) and Kaplan fibers (15°, 60°-90°). At higher flexion angles (60°-90°), sectioning the Kaplan fibers led to significantly greater internal rotation when compared with ALL sectioning. On simulated pivot-shift testing, ALL sectioning led to significantly increased internal rotation and anterior translation at 15° and 30°; sectioning of the Kaplan fibers led to significantly increased tibial internal rotation at 15° and 30° and anterior translation at 15°. No significant difference was found when anterior tibial translation was compared between the ACL/ALL- and ACL/Kaplan fiber-deficient states on simulated pivot-shift testing or isolated anterior tibial load. CONCLUSION: The ALL and Kaplan fibers restrain internal rotation in the ACL-deficient knee. Sectioning the Kaplan fibers led to greater tibial internal rotation at higher flexion angles (60°-90°) as compared with ALL sectioning. Additionally, the ALL and Kaplan fibers contribute to restraint of the pivot shift and anterior tibial translation in the ACL-deficient knee. CLINICAL RELEVANCE: This study reports that the ALL and distal iliotibial band Kaplan fibers restrain anterior tibial translation, internal rotation, and pivot shift in the ACL-deficient knee. Furthermore, sectioning the Kaplan fibers led to significantly greater tibial internal rotation when compared with ALL sectioning at high flexion angles. These results demonstrate increased rotational knee laxity with combined ACL and anterolateral extra-articular knee injuries and may allow surgeons to optimize the care of patients with this injury pattern.

Anterolateral Knee Extra-articular Stabilizers: A Robotic Study Comparing Anterolateral Ligament Reconstruction and Modified Lemaire Lateral Extra-articular Tenodesis.

BACKGROUND: Persistent clinical instability after anterior cruciate ligament (ACL) reconstruction may be associated with injury to the anterolateral structures and has led to renewed interest in anterolateral extra-articular procedures. The influence of these procedures on knee kinematics is controversial. Purpose/Hypothesis: The purpose was to investigate the biomechanical properties of anatomic anterolateral ligament (ALL) reconstruction and a modified Lemaire procedure (lateral extra-articular tenodesis [LET]) in combination with ACL reconstruction as compared with isolated ACL reconstruction in the setting of deficient anterolateral structures (ALL and Kaplan fibers). It was hypothesized that both techniques would reduce tibial internal rotation when combined with ACL reconstruction in the setting of anterolateral structure deficiency. STUDY DESIGN: Controlled laboratory study. METHODS: A 6 degrees of freedom robotic system was used to assess tibial internal rotation, a simulated pivot-shift test, and anterior tibial translation in 10 paired fresh-frozen cadaveric knees. The following states were tested: intact; sectioned ACL, ALL, and Kaplan fibers; ACL reconstruction; and an anterolateral extra-articular procedure (various configurations of ALL reconstruction and LET). Knees within a pair were randomly assigned to either ALL reconstruction or LET with a graft tension of 20 N and a randomly assigned fixation angle (30° or 70°). ALL reconstruction was then repeated and secured with a graft tension of 40 N. RESULTS: In the setting of deficient anterolateral structures, ACL reconstruction was associated with significantly increased residual laxity for tibial internal rotation (up to 4°) and anterior translation (up to 2 mm) laxity as compared with the intact state. The addition of ALL reconstruction or LET after ACL reconstruction significantly reduced tibial internal rotation in most testing scenarios to values lower than the intact state (ie, overconstraint). Significantly greater reduction in laxity with internal rotation and pivot-shift testing was found with the LET procedure than ALL reconstruction when compared with the intact state. Combined with ACL reconstruction alone, both extra-articular procedures restored anterior tibial translation to values not significantly different from the intact state with most testing scenarios (usually within 1 mm). CONCLUSION: Residual laxity was identified after isolated ACL reconstruction in the setting of ALL and Kaplan fiber deficiency, and the combination of ACL reconstruction in this setting with either ALL reconstruction or the modified Lemaire LET procedure resulted in significant reductions in tibiofemoral motion at most knee flexion angles, although overconstraint was also identified. ALL reconstruction and LET restored anterior tibial translation to intact values with most testing states. CLINICAL RELEVANCE: ALL reconstruction and lateral extra-articular tenodesis have been described in combination with intra-articular ACL reconstruction to address rotational laxity. This study demonstrated that both procedures resulted in significant reductions of tibial internal rotation versus the intact state independent of graft tension or fixation angle, although anterior tibial translation was generally restored to intact values. The influence of overconstraint with anterolateral knee reconstruction procedures has not been fully evaluated in the clinical setting and warrants continued evaluation based on the findings of this biomechanical study.

Use of Platelet-Rich Plasma Immediately After an Injury Did Not Improve Ligament Healing, and Increasing Platelet Concentrations Was Detrimental in an In Vivo Animal Model.

BACKGROUND: Limited information in basic science and clinical trials exists to determine if ligament healing may be accelerated with the use of biological adjuvants, such as platelet-rich plasma (PRP). However, there has been widespread acceptance of PRP for use in clinical practice, despite an inadequate understanding of its biological mechanism of action. PURPOSE: To determine whether a single dose of PRP could accelerate ligament healing and correspondingly improve histological characteristics and biomechanical properties when injected immediately postoperatively into the injured medial collateral ligament (MCL) of New Zealand White rabbits. STUDY DESIGN: Controlled laboratory study. METHODS: Eighty skeletally mature New Zealand White rabbits (160 knees) were used. The MCL was torn midbody to simulate a grade 3 tear. After an acute injury of the MCL, the administration of autologous PRP at 3 different platelet concentrations (0 million/uL, platelet-poor plasma [PPP]; 0.6 million/uL, 2 times the baseline [2× PRP]; and 1.2 million/uL, 4 times the baseline [4× PRP]) was performed and compared with a saline injection control in the contralateral knee. Histological analysis and a biomechanical endpoint characterization were utilized to assess ligamentous healing and compare it to a sham surgery group. RESULTS: The PPP ( P = .001) and 4× PRP ( P = .002) groups had a significantly lower collagen subscore than the sham surgery group. No other differences were observed among the treatment groups, including the vascularity subscore and overall ligament tissue maturity index score. Compared with saline-injected contralateral knees, the maximum load for PPP and 2× PRP was not significantly different ( P = .788 and .325, respectively). The maximum load and stiffness for knees treated with 4× PRP were significantly less than for the saline-treated contralateral knees ( P = .006 and .001, respectively). CONCLUSION: One single dose of PPP or 2× PRP at the time of injury did not improve ligament healing. In addition, 4× PRP negatively affected ligament strength and histological characteristics at 6 weeks after the injury. CLINICAL RELEVANCE: The current practice of treating knee ligament injuries with PRP may not improve healing at low doses of PRP. The decreased mechanical properties and histological appearance of the torn MCL suggest that high doses of PRP decrease the quality of repair tissue. Further in vivo studies are necessary to determine the dosing and timing of PRP administration after a ligament injury before the widespread use of PRP to treat ligament injuries is recommended.

Lateral Meniscus Posterior Root and Meniscofemoral Ligaments as Stabilizing Structures in the ACL-Deficient Knee: A Biomechanical Study.

BACKGROUND: The biomechanical effects of lateral meniscal posterior root tears with and without meniscofemoral ligament (MFL) tears in anterior cruciate ligament (ACL)-deficient knees have not been studied in detail. PURPOSE: To determine the biomechanical effects of the lateral meniscus (LM) posterior root tear in ACL-intact and ACL-deficient knees. In addition, the biomechanical effects of disrupting the MFLs in ACL-deficient knees with meniscal root tears were evaluated. STUDY DESIGN: Controlled laboratory study. METHODS: Ten paired cadaveric knees were mounted in a 6-degrees-of-freedom robot for testing and divided into 2 groups. The sectioning order for group 1 was (1) ACL, (2) LM posterior root, and (3) MFLs, and the order for group 2 was (1) LM posterior root, (2) ACL, and (3) MFLs. For each cutting state, displacements and rotations of the tibia were measured and compared with the intact state after a simulated pivot-shift test (5-N·m internal rotation torque combined with a 10-N·m valgus torque) at 0°, 20°, 30°, 60°, and 90° of knee flexion; an anterior translation load (88 N) at 0°, 30°, 60°, and 90° of knee flexion; and internal rotation (5 N·m) at 0°, 30°, 60°, 75°, and 90°. RESULTS: Cutting the LM root and MFLs significantly increased anterior tibial translation (ATT) during a pivot-shift test at 20° and 30° when compared with the ACL-cut state (both Ps < .05). During a 5-N·m internal rotation torque, cutting the LM root in ACL-intact knees significantly increased internal rotation by between 0.7° ± 0.3° and 1.3° ± 0.9° (all Ps < .05) except at 0° (P = .136). When the ACL + LM root cut state was compared with the ACL-cut state, the increase in internal rotation was significant at greater flexion angles of 75° and 90° (both Ps < .05) but not between 0°and 60° (all Ps > .2). For an anterior translation load, cutting the LM root in ACL-deficient knees significantly increased ATT only at 30° (P = .007). CONCLUSION: The LM posterior root was a significant stabilizer of the knee for ATT during a pivot-shift test at lower flexion angles and internal rotation at higher flexion angles. CLINICAL RELEVANCE: Increased knee anterior translation and rotatory instability due to posterior lateral meniscal root disruption may contribute to increased loads on an ACL reconstruction graft. It is recommended that lateral meniscal root tears be repaired at the same time as an ACL reconstruction to prevent possible ACL graft overload.