Ultrasound Shear Wave Elastography for Noninvasive Diagnosis of Acute Compartment Syndrome Using a Novel In Vivo Turkey Model.

INTRODUCTION: Acute Compartment Syndrome (ACS) is a severe trauma caused by elevated intra-muscle-compartment pressure (ICP). The current standard method for diagnosis is to insert a needle into the muscle sterilely under anesthesia. However, to secure the environment is sometimes not easy and leads to delays in diagnosis. Recently, we have focused on shear wave ultrasound elastography (SWE) as an alternative, which can be done concisely in unclean environment and without anesthesia. We would like to report the usefulness of SWE for ACS diagnosis using 2-pedal walking turkey model recently developed in our lab. MATERIALS AND METHODS: A total of 32 1-year-old Bourbon turkeys were used. 5% solution of chicken albumin was infused continuously into the tibialis cranialis (TC) muscle using IV pump. The ICP was increased stepwise from 0 to 50 mmHg. During the rising of ICP, the correlation between values of SWE (kPa) and ICP (mmHg) was measured. After the ICP reached 50 mmHg, half of the turkeys were maintained at this pressure for 2 hours and the rest for 6 hours. After infusion, a fasciotomy was performed on the half turkey. Half of the turkeys were euthanized after 2 weeks and the rest after 6 weeks. SWE of TC muscle and walking gait data on turkeys using a portable walkway system were measured weekly until euthanasia. At euthanasia, isometric tetanic muscle force (ITF) tests to TC muscle and histological evaluations were performed. RESULTS: SWE value (kPa) was highly significantly correlated to the actual ICP (mmHg) (R2 = 0.91). Stance of ACS side leg were significantly extended, and swing of the control side shortened from the second to the third week after ACS in the 6 hours infusion-no-fasciotomy group (P < 0.05*). ITF was significantly reduced mainly in the 6 hours infusion group (P < 0.05*). Histological evaluation revealed that in the 6 hours infusion and 6 weeks survival group, both the muscle fiber and intercellular distances were significantly expanded (P < 0.05). CONCLUSION: SWE seems to be a substitute measure of ICP in diagnosing ACS. With regard to our in vivo ACS model using turkey, survival at 50 mmHg ICP for 6 hours and 6 weeks post ACS would be an appropriate situation.

Relationship Between the Changes of Tendon Elastic Moduli With Ultrasound Shear Wave Elastography and Mechanical Compression Test.

OBJECTIVE: The purpose of this study was to investigate the consistency of the changes in the elastic modulus measured with ultrasound shear wave elastography (SWE) with changes measured through mechanical testing using tendons that were artificially altered by chemical modifications. METHODS: Thirty-six canine flexor digitorum profundus tendons were used for this experiment. To mimic tendon mechanical property changes induced by tendinopathy conditions, tendons were treated with collagenase to soften the tissue by collagen digestion or with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) to stiffen the tissues through chemical crosslinking. Tendons were randomly assigned to one of three groups: immersion in phosphate-buffered saline (PBS) as a control group (n = 12), collagenase treatment (n = 12) or EDC treatment (n = 12). Immediately following SWE measurement of each tendon, mechanical compression testing was performed as a gold standard to validate the SWE measurement. Both tests were conducted before and after treatment. RESULTS: The compressive modulus and SWE shear modulus significantly decreased after collagenase treatment. Conversely, both moduli significantly increased after EDC treatment. There was no significant difference in either modulus before or after PBS treatment. As a result of a regression analysis with the percentage change of the compressive modulus as the dependent variable and SWE shear modulus as the independent variable, the best-fit regression was found to be an exponential function and the coefficient of determination was 0.687. CONCLUSION: The changes in the compressive moduli and SWE shear moduli in tendons induced by chemical treatments were correlated by approximately 70%.

The Medial Tibial Plateau Can Be Used as a Direct Anatomical Reference for the Posterior Tibial Slope in Medial Unicompartmental Knee Arthroplasty.

There has been no consensus about how to determine the individual posterior tibial slope (PTS) intraoperatively. The purpose of this study was to investigate whether the tibial plateau could be used as a reference for reproducing individual PTS during medial unicompartmental knee arthroplasty (UKA). Preoperative computed tomography (CT) data from 48 lower limbs for medial UKA were imported into a three-dimensional planning software. Digitally reconstructed radiographs were created from the CT data as the lateral knee plain radiographs and the radiographic PTS angle was measured. Then, the PTS angles on the medial one-quarter and the center of the MTP (» and ½ MTP, respectively), and that on the medial tibial eminence (TE) were measured on the sagittal multiplanar reconstruction image. Finally, 20 lateral knee radiographs with an arthroscopic probe placed on the » and the ½ MTP were obtained intraoperatively, and the angle between the axis of the probe and the tangent line of the plateau was measured. The mean radiographic PTS angle was 7.9 ± 3.0 degrees (range: 1.7-13.6 degrees). The mean PTS angles on the » MTP, the ½ MTP, and the TE were 8.1 ± 3.0 degrees (1.2-13.4 degrees), 9.1 ± 3.0 degrees (1.4-14.7 degrees), and 9.9 ± 3.1 degrees (3.1-15.7 degrees), respectively. The PTS angles on the » MTP and the ½ MTP were strongly correlated with the radiographic PTS angle (r =0.87 and 0.80, respectively, p < 0.001). A statistically significant difference was observed between the mean angle of the radiographic PTS and the PTS on the TE (p < 0.01). The mean angle between the axis of the probe and the tangent line of the tibial plateau was -0.4 ± 0.9 degrees (-2.3-1.3 degrees) on the » MTP and -0.1 ± 0.7 degrees (-1.5-1.2 degrees) on the ½ MTP, respectively. An area from the medial one-quarter to the center of the MTP could be used as an anatomical reference for the individual PTS.

A direct referencing method of the tibial plateau for the posterior tibial slope in medial unicompartmental knee arthroplasty.

PURPOSE: There is no consensus on intraoperative references for the posterior tibial slope (PTS) in medial unicompartmental knee arthroplasty (UKA). An arthroscopic hook probe placed on the medial second quarter of the medial tibial plateau (MTP) in an anteroposterior direction may be used as a direct anatomical reference for the PTS. The purpose of this study is to investigate the availability and accuracy of this method. METHODS: Marginal osteophyte formation and subchondral depression of the MTP and angles between the bony MTP and the cartilage MTP were retrospectively evaluated using preoperative sagittal MRI of 73 knees undergoing medial UKA. In another 36 knees, intraoperative lateral knee radiographs with the probe placed on the MTP were prospectively taken in addition to the preoperative MRI. Then, angles between the bony MTP and the probe axis and angles between the preoperative bony MTP and the postoperative implant MTP were measured. RESULTS: Among 73 knees, one knee with grade 4 osteoarthritis had a posterior osteophyte higher than the most prominent point of the cartilage MTP. No subchondral depression affected the direct reference of the MTP. The mean angle between the bony MTP and the cartilage MTP was -0.8° ± 0.7° (-2.6°-1.0°, n = 72), excluding one knee with a "high" osteophyte. The mean angle between the bony MTP and the probe axis on the intraoperative radiograph was -0.6° ± 0.4° (-1.7-0.0, n = 36). The mean angle between the pre- and postoperative MTP was -0.5° ± 1.5° (-2.9°-1.8°). The root-mean-square (RMS) error of these two PTS angles was 1.6° with this method. CONCLUSION: Cartilage remnants, osteophyte formation and subchondral bone depression do not affect the direct referencing method in almost all knees for which medial UKA is indicated. When the posterior "high" osteophyte of the MTP is noted on preoperative radiography, preoperative MRI or CT scan is recommended to confirm no "high" osteophyte on the medial second quarter. The accuracy of this method seems equal to that of robotic-assisted surgery (the RMS error in previous reports, 1.6°-1.9°).

Referencing the substitute anteroposterior line of the tibia improves rotational alignment of the tibial component in medial unicompartmental knee arthroplasty.

BACKGROUND: There is no consensus regarding how best to determine the tibial rotational alignment in unicompartmental knee arthroplasty (UKA). The purpose of this study was to clarify whether using the substitute anteroposterior (sAP) line of the tibia, as has recently been proposed, can improve tibial rotation. METHODS: The study included 57 consecutive medial UKAs. From May 2015 to September 2016, 28 knees in 28 patients underwent UKA using the medial intercondylar ridge (MIR) line as the tibial anteroposterior (AP) reference (MIR group). From October 2016 to March 2018, 29 knees in 29 patients underwent UKA using the sAP line (sAP group). In both groups, the external rotation angle of the tibial component relative to a line perpendicular to the surgical epicondylar axis was measured using computed tomography-based three-dimensional preoperative planning software for TKA and UKA. RESULTS: The mean external rotation angles of the tibial component in the MIR and sAP groups were 5.2° ± 8.5° (range, -12.4° to 20.8°) and 0.7° ± 3.2° (range, -6.0° to 7.4°), respectively (unpaired t test, P = 0.014). The variation in the external rotation angle of the tibial component was significantly smaller in the sAP group than in the MIR group (F test, P < 0.0001), as was the number of the outliers with more than ±5° error (Fisher's exact test, P < 0.0001). CONCLUSIONS: The use of the sAP line as the AP reference could improve and stabilize the rotational orientation of the tibial component in UKA procedures.

Extra-articular synovial osteochondroma of the Hoffa's fat pad involving the patellar tendon: A case report and literature review.

Synovial osteochondroma (SO) is a relatively uncommon tumor affecting the synovial joints that is characterized by the development of hyaline cartilage from the synovial membrane. The basic pathophysiology of SO is thought to be the metaplastic change of the synovium to hyaline cartilage. Large extra- or para-articular lesions in the Hoffa's fat pad are relatively uncommon. A 56-year-old woman complained of knee pain associated with a large lesion on the anterior of the right knee. She also had restricted range of motion in the knee. Examination revealed an elastic hard 8x9-cm lesion involving the patellar tendon. Computed tomography and magnetic resonance imaging demonstrated a mosaic-intensity mass lesion in the inferior side of the Hoffa's fat pad as well as the patellar tendon. The patient underwent needle biopsy. Histological analysis revealed a solitary SO. There were no atypical features suggestive of malignancy and the mass was resected marginally. The patient had no recurrence or knee functional disorder 3 years postoperatively. There are no reports of SO involving the patellar tendon with restriction of range of motion. Removal of the mass lesion for management for SO, as in the present case, is unusual. To the best of our knowledge, this is the first case of extra-articular SO in the Hoffa's fat pad involving the patellar tendon causing a restriction of range of motion of the knee. Marginal surgical resection improved knee function.

Obliquity of tibial component after unicompartmental knee arthroplasty.

BACKGROUND: The native knee joint line is varus relative to the tibia and remains parallel to the floor during gait even with varus lower-limb alignment. We investigated the desired degree of frontal obliquity for positioning the tibial component during unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively analyzed full-leg, standing, hip to ankle digital radiographs from 107 osteoarthritic knees. We measured the hip-knee-ankle (HKA) angle, the tibial joint-line orientation angle (JLOA), which indicates the angle of the joint line (tibial component) relative to the floor, and the medial proximal tibial angle (MPTA), which is the angle of the joint line (tibial component) relative to the tibial mechanical axis, before and after UKA in the coronal plane. RESULTS: The preoperative HKA angle (mean 7.3°, standard deviation (SD) 3.0) was significantly higher than the postoperative HKA angle (mean 3.4°, SD 3.0, P < 0.0001). The preoperative MPTA (mean 4.8°, SD 2.1) did not significantly differ from the postoperative MPTA (mean 4.5°, SD 3.0, P = 0.47). The mean postoperative JLOA was parallel to the floor (JLOA; 0.2°, SD 3.6). CONCLUSION: When the tibial component is positioned along the natural joint slope restoring pre-disease alignment of the overall lower limb in the coronal plane, the tibial component was positioned parallel to the floor. When UKA is indicated for the medial osteoarthritis patient, the surgeon should install the tibial component four to five degrees varus to the tibial mechanical axis to maintain joint-line parallelism.

Activation of the renin-angiotensin system in mice aggravates mechanical loading-induced knee osteoarthritis.

Epidemiological studies have shown an association between hypertension and knee osteoarthritis (OA). The purpose of this study was to investigate whether activation of the renin-angiotensin system (RAS) can aggravate mechanical loading-induced knee OA in mice. Eight-week-old male Tsukuba hypertensive mice (THM) and C57BL/6 mice were divided into running and non-running groups. Mice in the running group were forced to run (25 m/min, 30 min/day, 5 days/week) on a treadmill. All mice in the four groups (n=10 in each group) were euthanized after 0, 2, 4, 6, or 8 weeks of running or natural breeding. Cartilage degeneration in the left knees was histologically evaluated using the modified Mankin score. Expression of Col X, MMP-13, angiotensin type 1 receptor (AT1R), and AT2R was examined immunohistochemically. To study the effects of stimulation of the AT1R in chondrocytes by mechanical loading and/or Angiotensin II (AngII) on transduction of intracellular signals, phosphorylation levels of JNK and Src were measured in bovine articular chondrocytes cultured in three-dimensional agarose scaffolds. After 4 weeks, the mean Mankin score for the lateral femoral condylar cartilage was significantly higher in the THM running group than in the C57BL/6 running group and non-running groups. AT1R and AT2R expression was not detected at 0 weeks in any group but was noted after 4 weeks in the THM running group. AT1R expression was also noted at 8 weeks in the C57BL/6 running group. The expression levels of AT1R, COL X, and MMP-13 in chondrocytes were significantly higher in the THM running group than in the control groups. Positive significant correlations were noted between the Mankin score and the rate of AT1R-immunopositive cells, between the rates of AT1R- and Col X-positive cells, and between the rates of AT1R- and AT2R-positive cells. The phosphorylation level of JNK was increased by cyclic compression loading or addition of AngII to the cultured chondrocytes and was reversed by pretreatment with an AT1R blocker. A synergistic effect on JNK phosphorylation was observed between compression loading and AngII addition. Transgene activation of renin and angiotensinogen aggravated mechanical load-induced knee OA in mice. These findings suggest that AT1R expression in chondrocytes is associated with early knee OA and plays a role in the progression of cartilage degeneration. The RAS may be a common molecular mechanism involved in the pathogenesis of hypertension and knee OA.

Cyclic compressive loading activates angiotensin II type 1 receptor in articular chondrocytes and stimulates hypertrophic differentiation through a G-protein-dependent pathway.

Angiotensin II type 1 receptor (AT1R) appears to have a mechanosensing function in a number of cell types. The purpose of this study was to examine whether AT1R expressed in articular chondrocytes is involved in osteoarthritis (OA) progression in vivo and whether cyclic compressive loading activates the AT1R and stimulates hypertrophic differentiation of chondrocytes in vitro. The relationships between the modified Mankin score for cartilage degeneration and the expression of AT1R and type X collagen (Col X) were studied in mouse knees with OA induced using the destabilization-of-medial-meniscus model. Cyclic compressive loads were applied to cultured bovine articular chondrocytes in three-dimensional agarose scaffolds. Expression of Col X and runt-related transcription factor 2 (Runx2) was analyzed using RT-PCR and western blotting. We dissected the downstream pathway for intracellular signal transductions of AT1R including G-protein-dependent and G-protein-independent pathways. Positive significant correlations between the Mankin score and the rate of AT1R-immunopositive cells and between the rates of AT1R and Col X expression were noted. The expression of Col X and Runx2 was increased by compressive loading but suppressed by addition of olmesartan, an Ang II receptor blocker, to the agarose scaffolds. Compressive loading upregulated the phosphorylation of c-Jun N-terminal kinase (JNK), Src, and STAT1, but olmesartan significantly suppressed only JNK phosphorylation. We conclude that AT1R expressed by articular chondrocytes may be involved in OA progression in vivo. Mechanical stress can activate AT1R and stimulate hypertrophic differentiation of chondrocytes through the G-protein-dependent pathway. AT1R has a mechanosensing function in chondrocytes and may be a new therapeutic target in OA.

Anteroposterior Rotational References of the Tibia for Medial Unicompartmental Knee Arthroplasty in Japanese Patients.

BACKGROUND: In unicompartmental knee arthroplasty (UKA), there is no consensus regarding how to determine the anteroposterior (AP) reference of the tibia. A number of surgeons in Japan perform the sagittal saw cut using the medial intercondylar ridge (MIR) of the tibia according to surgical manuals. However, there is no theoretical basis for this practice. METHODS: Preoperative computed tomography data from 32 lower limbs of 31 Japanese patients who received UKA were used. First, the angles between the surgical epicondylar axis and the MIR and the substitute AP (sAP) line connecting the medial border of the patellar tendon at the articular surface level and the medial intercondylar tubercle were measured. Next, the mediolateral (ML)/AP ratio of the tibial cut surface was measured when cut parallel to the MIR and sAP line. Finally, the ML/AP ratio of the tibial component was investigated in 4 contemporary UKA implants. RESULTS: The MIR and sAP line were externally rotated 94.9° ± 4.1° and 90.4° ± 3.6° relative to the surgical epicondylar axis, respectively. Compared with a cut parallel to the MIR, the mean ML/AP ratio of the cut surface was significantly larger, and the ML/AP ratio was closer to the ML/AP ratio of the components for a cut parallel to the sAP line. CONCLUSION: Obtaining the tibial AP orientation is one of the key steps not only in total knee arthroplasty but also in UKA. The sagittal cut referencing the sAP line provides better AP rotation and fitting of the tibia in UKA than referencing the MIR.

The Development of a Novel Bone Filler, Titanium Wire Ball.

In designing bone fillers, hardness has heretofore not been a major concern. Fillers are typically very hard and thus often accelerate the collapse of the adjacent bones. We developed a novel, relatively soft bone filler, whose hardness is similar to the human cancellous bone. The structure is simple: a 0.14-mm-diameter pure titanium wire was rolled and folded with both ends buried in the central portion, resulting in a ball of 4-mm diameter with 83% internal void ratio, having 300-500 µm internal gaps. The balls are chemically washed in an acidic solution at the end of the manufacturing process. We call this new filling device titanium wire balls (TWBs). We implanted TWBs into the medial condyle of the right tibiae of twelve adult Japanese white rabbits, and histologically evaluated the results. Four weeks after implantation, the spaces in the TWBs were fully calcified; the TWBs, the calcified tissues in them and the cancellous bones surrounding them were all connected with each other. In conclusion, we developed a novel bone filler that has similar hardness to the human cancellous bone and an 83% internal void ratio, with 300-500 µm internal gaps. Four weeks after implantation, the spaces in TWBs were fully calcified and connected to the surrounding cancellous bones.

Activating types 1 and 2 angiotensin II receptors modulate the hypertrophic differentiation of chondrocytes.

A local tissue-specific renin-angiotensin system (local RAS) has been identified in many organs. However, no report has described the role of a local RAS in the hypertrophic differentiation of chondrocytes. To examine the role of a local RAS in the hypertrophic differentiation, we activated angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) separately in the cell line ATDC5, which involves differentiation from mesenchymal stem cells to hypertrophic chondrocytes. Activation of AT1R suppressed and activation of AT2R enhanced the expression of markers of hypertrophic differentiation, including type X collagen, matrix metalloproteinase 13 and runt-related transcription factor 2.