Balance of the prooxidant and antioxidant system is associated with mortality in critically ill patients.

It is well known that oxidative stress causes certain diseases and organ damage. However, roles of oxidative stress in the acute phase of critical patients remain to be elucidated. This study aimed to investigate the balance of oxidative and antioxidative system and to clarify the association between oxidative stress and mortality in critically ill patients. This cohort study enrolled 247 patients transported to our emergency department by ambulance. Blood was drawn on hospital arrival, and serum derivatives of reactive oxidant metabolites (dROMs, oxidative index) and biological antioxidant potential (BAP, antioxidative index) were measured. Modified ratio (MR) is also calculated as BAP/dROMs/7.51. There were 197 survivors and 50 non-survivors. In the non-survivors, dROMs were significantly lower (274 vs 311, p<0.01), BAP was significantly higher (2,853 vs 2,138, p<0.01), and MR was significantly higher (1.51 vs 0.92, p<0.01) compared to those in the survivors. The AUC of MR was similar to that for the APACHE II score. Contrary to our expectations, higher BAP and lower dROMs were observed on admission in non-survivors. This may suggest that the antioxidative system is more dominant in the acute phase of severe insults and that the balance toward a higher antioxidative system is associated with mortality.

Three-dimensional computed tomography confirmed that the meniscal root attachments and meniscofemoral ligaments are morphologically consistent.

PURPOSE: To clarify the characteristic features of the meniscal root attachments, meniscofemoral ligaments (MFLs), and related osseous landmarks on three-dimensional images using computed tomography. METHODS: Twenty-eight non-paired, formalin-fixed human cadaveric knees were evaluated in this study. The meniscal root attachments were identified and marked. Three-dimensional images were obtained after applying a contrast agent to the entire meniscal surfaces and MFLs, then the morphology of the meniscal root attachments and MFLs, and their positional relationships with osseous landmarks, were analyzed. RESULTS: Parsons' knob divided the medial meniscal anterior root attachment and lateral meniscal anterior root attachment on the anterior portion of the tibial plateau. The medial meniscal posterior root attachment was near the medial intercondylar tubercle. The lateral meniscal posterior root attachment (LMPRA) was closer to the lateral intercondylar tubercle. Both root attachments were near the posterior intercondylar fossa. The positional relationships between the meniscal root attachments and related osseous landmarks were consistent in all specimens. The MFLs originated from the lateral meniscus posterior horn, and the anterior MFL was closer to the LMPRA than the posterior MFL. The posterior MFL originated at approximately the midpoint between the LMPRA and the most posterior margin of the lateral meniscus. CONCLUSION: This study showed that the relationships between the characteristic features of the meniscal root attachments, MFLs, and related osseous landmarks were consistent. The clinical relevance of this study is that it improved understanding of the anatomy of the meniscal root attachments and MFLs.

How to Safely Prevent Venous Thromboembolism in Severe Trauma Patients.

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.

Morphology of the Insertions of the Superficial Medial Collateral Ligament and Posterior Oblique Ligament Using 3-Dimensional Computed Tomography: A Cadaveric Study.

PURPOSE: To describe the insertions of the superficial medial collateral ligament (sMCL) and posterior oblique ligament (POL) and their related osseous landmarks. METHODS: Insertions of the sMCL and POL were identified and marked in 22 unpaired human cadaveric knees. The surface area, location, positional relations, and morphology of the sMCL and POL insertions and related osseous structures were analyzed on 3-dimensional images. RESULTS: The femoral insertion of the POL was located 18.3 mm distal to the apex of the adductor tubercle (AT). The femoral insertion of the sMCL was located 21.1 mm distal to the AT and 9.2 mm anterior to the POL. The angle between the femoral axis and femoral insertion of the sMCL was 18.6°, and that between the femoral axis and the POL insertion was 5.1°. The anterior portions of the distal fibers of the POL were attached to the fascia cruris and semimembranosus tendon, whereas the posterior fibers were attached to the posteromedial side of the tibia directly. The tibial insertion of the POL was located just proximal and medial to the superior edge of the semimembranosus groove. The tibial insertion of the sMCL was attached firmly and widely to the tibial crest. The mean linear distances between the tibial insertion of the POL or sMCL and joint line were 5.8 and 49.6 mm, respectively. CONCLUSIONS: This study used 3-dimensional images to assess the insertions of the sMCL and POL and their related osseous landmarks. The AT was identified clearly as an osseous landmark of the femoral insertions of the sMCL and POL. The tibial crest and semimembranosus groove served as osseous landmarks of the tibial insertions of the sMCL and POL. CLINICAL RELEVANCE: By showing further details of the anatomy of the knee, the described findings can assist surgeons in anatomic reconstruction of the sMCL and POL.

Morphology of the fibular insertion of the posterolateral corner and biceps femoris tendon.

PURPOSE: To clarify the fibular head insertion of the fibular collateral ligament (FCL), popliteofibular ligament (PFL), and biceps femoris tendon and related osseous landmarks on three-dimensional (3-D) images. METHODS: Twenty-one non-paired, formalin-fixed human cadaveric knees were evaluated in this study. The fibular head insertions of the FCL, PFL and biceps femoris tendon were identified and marked. 3-D images were created, and the surface area, location, positional relationships, and morphology of the fibular insertions of the FCL, PFL, and biceps femoris tendon and related osseous structures were analysed. RESULTS: The fibular head had a unique pyramidal shape, and the relationships of the fibular insertion of the FCL, PFL, and biceps femoris tendon were consistent. The fibular head consists of three aspects: lateral aspect, posterior aspect, and proximal tibiofibular facet. The insertions of the FCL, PFL, and biceps femoris tendon were attached to the centre from the distal side of the lateral aspects of the fibular head, posterior aspect of the fibular styloid process, and lateral aspect surrounding the FCL, respectively. The mean surface areas of the FCL and PFL fibular insertions were 100.1 ± 29.5 and 18.5 ± 7.2 mm2, respectively. CONCLUSION: This study showed that the relationships between the characteristic features of the fibular head and insertions of the FCL, PFL, and biceps femoris tendon were consistent. The clinical relevance of this study is that it improves understanding of the anatomy of the insertions of the PLC and biceps femoris tendon.

Morphology of insertion sites on patellar side of medial patellofemoral ligament.

PURPOSE: The purpose of this study was to clarify the insertion sites on the patellar side of the medial patellofemoral ligament (MPFL). METHODS: A total of 35 nonpaired human cadaveric knees were used in this study. After identification of the MPFL, the insertion sites on the patellar side of the MPFL were marked. Three-dimensional images were created, and the location and morphology of these insertion sites were analysed. RESULTS: The morphology of the insertion sites on the patellar side of the MPFL was consistent. The proximal fibres of the MPFL were inserted to the deep fascia of the vastus medialis obliquus (VMO) and medial margin of the vastus intermedius (VI). The distal fibres of the MPFL were inserted to the medial margin of the patella directly. The insertion lengths of the VMO, VI, and patella were 26.7 ± 5.0, 28.5 ± 4.4, and 18.5 ± 4.4 mm, respectively. The rate of the vertical distance from the superior pole of the patella to the superior edge of the MPFL in relation to the total patellar height was 12 ± 4.4 %. At the distal edge, the rate was 58 ± 9.6 %. CONCLUSION: The insertion sites on the patellar side of the MPFL were consistent. The MPFL inserted into the VMO and VI was significantly longer than into the patella. The clinical relevance of this study is to improve understanding of the anatomy of the insertion sites on the patellar side of the MPFL and the pathophysiology of patellar dislocation.

Morphology of the femoral insertion site of the medial patellofemoral ligament.

PURPOSE: The purpose of this study was to identify the femoral insertion of the medial patellofemoral ligament (MPFL) and related osseous landmarks. METHODS: A total of 31 unpaired human cadaveric knees were studied. The MPFL was identified, and the site of its femoral insertion was marked. Three-dimensional images were created, and the location and morphology of the femoral insertion of the MPFL and related osseous structures were analyzed. RESULTS: The MPFL was identified in all knees. The femoral insertion of the MPFL was elliptical in shape, and the mean surface area was 56.5 ± 16.9 mm(2). The characteristic features of the femoral insertion of the MPFL could not be identified, but the adductor tubercle was clearly identified in all knees. The centre of the femoral insertion of the MPFL was 10.6 ± 2.5 mm distal to the apex of the adductor tubercle on the long axis of the femur, and the position of the insertion site was consistent in all knees. CONCLUSION: The adductor tubercle was clearly identified as an osseous landmark. The femoral insertion of the MPFL was approximately 10 mm distal to the adductor tubercle. These findings may improve understanding of the anatomy of the femoral insertion of the MPFL and may assist surgeons in performing anatomical reconstruction.

Morphology of the femoral insertion of the lateral collateral ligament and popliteus tendon.

PURPOSE: To clarify the femoral insertion of the lateral collateral ligament (LCL) and popliteus tendon (PT) and related osseous landmarks on three-dimensional images. METHODS: Twenty-six non-paired, formalin-fixed human cadaveric knees were evaluated in this study. Femoral insertion of the LCL and PT was identified and marked. Three-dimensional images were created, and the surface area, location, positional relationships, and morphology of the femoral insertion of the LCL, PT, and related osseous structures were analysed. RESULTS: The mean surface areas of the LCL and PT femoral insertions were 55.8 ± 25.0 and 52.5 ± 24.2 mm(2), respectively. Variations in the positional relationships between the LCL and PT insertions (PT inserted parallel and posterior to the LCL insertion to the long axis of the femur) were observed. The lateral epicondyle and popliteal sulcus could be clearly identified as osseous landmarks on three-dimensional images in all knees. Most of the LCL was inserted postero-distal to the apex of the lateral epicondyle, and the PT was inserted at the anterior end of the popliteal sulcus in all knees. CONCLUSION: We observed variation in the positional relationship between the femoral insertion of the LCL and PT. However, the relationships between their insertions and osseous landmarks were consistent. The findings of this study contribute to the understanding of the PLC osseous anatomy and should assist surgeons in performing PLC surgery with a more anatomic perspective.

Morphology of the popliteomeniscal fascicles around the popliteal hiatus on three-dimensional images reconstructed from 7 T magnetic resonance imaging: A cadaveric study.

BACKGROUND: This study aimed to clarify the characteristic features of the anteroinferior and posterosuperior popliteomeniscal fascicles (aiPMF and psPMF, respectively) and popliteal hiatus using three-dimensional (3D) reconstructions of 7 T magnetic resonance imaging (MRI) arthrography. METHODS: Six knees from human cadavers fixed using the Thiel embalming method were examined using 7 T MRI arthrography. 3D Images of the structures around the popliteal hiatus were reconstructed. Morphologies of the psPMF, aiPMF, and popliteal hiatus were investigated and their positional relationships analyzed. RESULTS: The PMFs attached to the periphery of the lateral meniscus (LM) to form the popliteal hiatus. Each coursed in an oblique direction. The mean length of the psPMF and aiPMF attachments to the LM were 6.8 and 21.6 mm, respectively; mean popliteal hiatus length was 12.8 mm. These lengths corresponded to 7.5%, 24.3%, and 14.5% of the total length of the LM, respectively. The aiPMF was thick near the lateral aspect of the articular capsule and became thinner towards the posteromedial aspect of the LM. The psPMF was thick near the posterior aspect of the articular capsule and became thinner towards the posterolateral aspect of the LM. CONCLUSION: Morphological properties of the aiPMF, psPMF, their attachments to the LM, and the popliteal hiatus were consistent across the cadaver specimens examined. Each PMF was thin near the popliteal hiatus and became thicker towards its attachment to the articular capsule. These findings may be useful for anatomical repair for the LM hypermobility.

Characteristics and outcomes of out-of-hospital cardiac arrest in a hilly area: Utstein Registry data from the Nagasaki Medical Region, Japan.

Aim: To analyze characteristics and investigate prognostic indicators of out-of-hospital cardiac arrest (OHCA) in a hilly area in Japan. Methods: A retrospective population-based study was conducted using the Utstein Registry for 4280 OHCA patients in the Nagasaki Medical Region (NMR) registered over the 10-year period from 2011 to 2020. The main outcome measure was a favorable cerebral performance category (CPC 1-2). Sites at which OHCA occurred were classified into "sloped places (SPs)" (not easily accessible by emergency medical services [EMS] personnel due to slopes) and "accessible places (APs)" (EMS personnel could park an ambulance close to the site). The characteristics and prognosis based on CPC were compared between SPs and APs, and multivariable analysis was performed. Results: No significant improvement in prognosis occurred in the NMR from 2011 to 2020. Prognosis in SPs was significantly worse than that in APs. However, multivariable analysis did not identify SP as a prognostic indicator. The following factors were associated with survival and CPC 1-2: age group, witness status, first documented rhythm, bystander-initiated cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use, use of mechanical CPR (m-CPR) device or esophageal obturator airway (EOA), and year. Both m-CPR and EOA use were associated with a poor prognosis. Conclusion: In a hilly area, OHCA patients in SPs had a worse prognosis than those in APs, but SPs was not significantly associated with prognosis by multivariable analysis. Interventions to increase bystander-initiated CPR and AED use could potentially improve outcomes of OHCA in the NMR.

Morphology of the proximal tibiofibular joint and ligaments using three-dimensional computed tomography: A cadaveric study.

BACKGROUND: The aim of our study was to clarify the morphology of the proximal tibiofibular joint (PTFJ), insertion sites of the proximal tibiofibular ligaments (PTFLs), and related osseous landmarks on three-dimensional (3D) computed tomography (CT) images. METHODS: Cadaveric knees were evaluated by dissection and 3D CT imaging. The anterior PTFL (A-PTFL) and posterior PTFL (P-PTFL) were isolated, and their tibial and fibular insertion sites were identified. The morphology and location of insertion sites and their positional relationships with osseous structures were analyzed on 3D CT images. RESULTS: The A-PTFL comprised up to four bundles, and the P-PTFL comprised two bundles. The mean length of the A-PTFL and P-PTFL was 11.3 mm and 10.3 mm, respectively. On the tibial side of the PTFJ, bony prominences were present at the A-PTFL and P-PTFL insertion sites and were clearly identified as osseous landmarks in all knees. On the fibular side, the A-PTFL and P-PTFL insertion sites were at the edge of the triangular pyramid of the fibular head. The mean PTFJ area was 198.8 mm2, and the mean inclination angle between PTFJ and tibial plane was 38.4°. There was an inverse correlation between the PTFJ surface area and the inclination angle. CONCLUSION: The present study clearly identified PTFL insertion sites on the tibia and fibula and showed the relationships between these insertions and osseous landmarks. These data improve our understanding of the anatomy of PTFL insertions, which may assist surgeons in performing anatomical reconstruction.

Morphology of the quadriceps tendon and its patella insertion site on three-dimensional computed tomography and magnetic resonance imaging: A cadaveric study.

AIM: This study was conducted to clarify the morphological properties of the quadriceps tendon (QT) and its patella insertion site using three-dimensional computed tomography and magnetic resonance imaging. METHODS: Twenty-one right knees from human cadavers were evaluated using three-dimensional computed tomography and magnetic resonance imaging. The morphologies of the QT and its patella insertion site were evaluated, along with intra-tendon differences in length, width, and thickness. RESULTS: The QT insertion site on the patella was dome-shaped without characteristic bony features. The mean surface area of the insertion site was 502.5 ± 68.5 mm2 (range, 336.0-610.7). The QT was longest 2.0 mm lateral to the central width of the insertion and gradually became shorter toward both edges (mean length, 59.7 ± 8.3 mm). The QT was widest at the insertion site (mean width, 39.1 ± 5.3 mm) and gradually became narrower toward the proximal side. The QT was thickest 2.0 mm medial to the center (mean thickness, 11.4 ± 1.9 mm). CONCLUSION: The morphological properties of the QT and its insertion site were consistent. The characteristics of the QT graft depend on the harvested region.

Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation.

OBJECTIVE: Programmed cell death-1 (PD-1) is a member of the CD28 superfamily that delivers negative signals on interaction with its 2 ligands, PD-L1 and PD-L2. We studied the contribution of the PD-1 pathway to regulation of T cells that promote atherosclerotic lesion formation and inflammation. METHODS AND RESULTS: We show that compared with Ldlr-/- control mice, Pd1-/-Ldlr-/- mice developed larger lesions with more abundant CD4+ and CD8+ T cells and macrophages, accompanied by higher levels of serum tumor necrosis factor-α. Iliac lymph node T cells from Pd1-/-Ldlr-/- mice proliferated more to αCD3 or oxidized low-density lipoprotein stimulation compared with controls. CD8+ T cells from Pd1-/-Ldlr-/- mice displayed more cytotoxic activity compared with controls in vivo and in vitro. Administration of a blocking anti-PD-1 antibody increased lesional inflammation in hypercholesterolemic Ldlr-/- mice with more lesional T cells and more activated T cells in paraaortic lymph nodes. The changes in lesional T-cell content when PD-1 was absent or blocked were also observed in bone marrow chimeric Ldlr-/- mice lacking PD-L1 and PD-L2 on hematopoietic cells. CONCLUSIONS: PD-1 has an important role in downregulating proatherogenic T-cell responses, and blockade of this molecule for treatment of viral infections or cancer may increase risk of cardiovascular complications.

PCL to graft impingement pressure after anatomical or non-anatomical single-bundle ACL reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) graft impingement against the posterior cruciate ligament (PCL) has been postulated, but not thoroughly investigated. PURPOSE: To evaluate PCL impingement pressure and biomechanical stability with different tibial and femoral tunnel positions in ACL reconstruction. METHODS: In 15 porcine knees, the impingement pressure between ACL and PCL was measured using pressure sensitive film before and after ACL single-bundle reconstruction. ACL reconstructions were performed in each knee with three different tibial and femoral tunnel position combinations: (1) tibial antero-medial (AM) tunnel to femoral AM tunnel (AM-AM), (2) tibial postero-lateral (PL) tunnel to femoral High-AM tunnel (PL-High-AM) and (3) tibial AM tunnel to femoral High-AM tunnel (AM-High-AM). Anterior tibial translation (ATT) was evaluated after each ACL reconstruction using robotic/universal force-moment sensor testing system. RESULTS: There was no significant difference of the impingement pressure between AM and AM, PL-High-AM reconstructed groups and intact ACL. Only AM-High-AM ACL reconstruction group showed significantly higher impingement pressure compared with intact ACL. With regard to ATT, AM-AM group had significantly higher stiffness than PL-High-AM group. CONCLUSION: Anatomical ACL reconstruction does not cause PCL impingement and it has biomechanical advantage in ATT when compared with non-anatomical ACL reconstructions in porcine knee. For the clinical relevance, in the anatomical ACL reconstruction, no ACL-PCL impingement is found.

In vitro and in vivo AM and PL tunnel positioning in anatomical double bundle anterior cruciate ligament reconstruction.

BACKGROUND: There have been few studies investigating the correct anatomical femoral and tibial tunnel placement in double bundle anterior cruciate ligament (ACL) reconstruction. OBJECTIVE: To compare anteromedial (AM) and posterolateral (PL) tunnel positions in anatomical double bundle ACL reconstruction in human cadaver and patient knees. MATERIALS AND METHODS: Fifteen fresh-frozen non-paired adult human knees and 27 patients (27 knees) were evaluated. In the cadaver knees, AM and PL bundles were identified by their difference in tension patterns. Their femoral centers were marked with a K-wire, and cut from the femoral insertion site. After this, each bundle was divided at the tibial side. The center of each bundle insertion was again marked with a K-wire, and 5-7-mm tunnels were drilled with transportal or outside-in technique. In patient knees, each tunnel was made according to the native ACL foot print and bony landmarks using transtibial technique (n = 5) and transportal technique (n = 22). Tunnel placement was evaluated using a C-arm X-ray device and 3D CT. For the femoral side assessment, Bernard and Hertel's technique was used. For the tibial side assessment, Amis and Jakob's technique was used. RESULTS: The femoral AM tunnel in the cadaver knees was placed in a significantly deeper position when compared to patient knees. There was no significant difference in the AM vertical placement or in the PL tunnel placement in the femur. No significant differences were observed in the tibial tunnel placements between cadaver and patient knees. CONCLUSION: In vivo positioning of the femoral AM bundle differed significantly from the in vitro positioning.

Analysis of characteristics required for gait evaluation of patients with knee osteoarthritis using a wireless accelerometer.

BACKGROUND: Knee osteoarthritis (KOA) is associated with reduced quality of life due to knee pain and gait disturbance. However, the evaluation of KOA is mainly based on images and patient-reported outcome measures (PROMs), which are said to be insufficient for functional evaluation. Recently, gait analysis using an accelerometer has been used for functional evaluation of KOA patients. Nevertheless, evaluation of the entire body motion is insufficient. The aim of this study was to clarify the gait characteristics of KOA patients using the distribution of scalar products and the interval time of heel contact during spontaneous walking and to compare them with healthy subjects. METHODS: Participants wore a three-axis accelerometer sensor on the third lumbar vertebra and walked for 6 min on a flat path at a free walking speed. The sum of a composite vector (CV) scalar product and a histogram for distribution were used for body motion evaluation. The CV consisted of a synthesis of acceleration data from three axes. In addition to the summation of the CV, a histogram can be created to evaluate in detail the magnitude of the waves. The amount of variation was measured in the left-right and front-back directions. Variability was evaluated from the distribution of heel contact duration between both feet measured from the vertical acceleration. RESULTS: KOA patients showed a smaller sum of CV that converged to small acceleration in the distribution when compared with healthy subjects. In the KOA group, the amount of variation in the forward and backward directions was greater than that in the forward direction. The variability of heel-ground interval time was greater in the KOA group than in healthy subjects. CONCLUSION: KOA patients walked with less overall body movement, with limited movable range of the knee joint and pain-avoiding motion. The gait of the KOA group was considered unstable, with long time intervals between peaks. The increase in the amount of forward variation was thought to be due to the effect of trunk forward bending during walking. The clinical relevance of this study is that it was possible to evaluate KOA patients' gait quantitatively and qualitatively.

Trauma induces expansion and activation of a memory-like Treg population.

CD4+ regulatory T cells (Tregs) are acutely activated by traumatic injury, which suggests that they may react to injury with similar kinetics as memory T cells. Here, we used a mouse burn trauma model to screen for memory-like T cell responses to injury by transferring T cells from sham or burn CD45.1 mice into CD45.2 mice and performing secondary injuries in recipient mice. Among all T cell subsets that were measured, only Tregs expanded in response to secondary injury. The expanded Tregs were a CD44high /CD62Llow subpopulation, markers indicative of memory T cells. CyTOF (cytometry by time-of-flight) mass cytometry was used to demonstrate that injury-expanded Tregs expressed higher levels of CD44, CTLA-4, ICOS, GITR, and Helios than Tregs from noninjured mice. Next, we tested whether a similar population of Tregs might react acutely to burn trauma. We observed that Tregs with a phenotype that matched the injury-expanded Tregs were activated by 6 h after injury. To test if Treg activation by trauma requires functional MHC class II, we measured trauma-induced Treg activation in MHC class II gene deficient (MHCII-/- ) mice or in mice that were given Fab fragment of anti-MHC class II antibody to block TCR activation. Injury-induced Treg activation occurred in normal mice but only partial activation was detected in MHCII-/- mice or in mice that were given Fab anti-MHCII antibody. These findings demonstrate that trauma activates a memory-like Treg subpopulation and that Treg activation by injury is partially dependent on TCR signaling by an MHC class II dependent mechanism.

The expression of repulsive guidance molecule a after traumatic brain injury: Time-course changes in gene expression in a murine model of controlled cortical impact.

INTRODUCTION: Repulsive guidance molecule a (RGMa) is a key protein that negatively regulates neuronal regeneration as its inhibition enhances axonal growth and promotes functional recovery in animal models of spinal cord injury. However, the role of RGMa in traumatic brain injury (TBI) remains elusive. This study aimed to clarify TBI-responsive RGMa expression in a murine model. METHODS: Adult male C57BL/6J mice were subjected to controlled cortical impact. Brains were extracted 6 hours and 1, 3, 7, 14 and 21 days after injury (n = 6 in each group). Changes in the messenger RNA (mRNA) expression of RGMa and its receptor, neogenin, were evaluated by quantitative polymerase chain reaction in the damaged area of the cortex and contralateral cortex, along with expression measurement of inflammation-related molecules. Neurological deficit was also assessed by the cylinder test. RESULTS: Neurological score was consistently lower in the TBI group compared to the sham group throughout the experimental period. The mRNA expressions of representative inflammatory cytokine TNF-α and chemokine receptor CCR2 were remarkably increased in the injured cortex on day 1 and gradually decreased over time, although remaining at higher values at least until day 14. The mRNA expressions of RGMa and neogenin were significantly suppressed in the damaged cortex until day 3. Interestingly, RGMa expression was suppressed most on day 1 and recovered over time. CONCLUSION: In the acute phase of TBI, gene expression of inflammatory cytokines significantly increased, and gene expressions of RGMa and neogenin significantly decreased in the inflammatory milieu of the damaged area. Despite the subsequent remission of inflammation, RGMa gene expression recovered to the normal level 1 week after TBI. Intrinsic regenerative response to acute brain injury might be hampered by the following recovery of RGMa expression, hinting at the possibility of functional RGMa inhibition as a new, effective maneuver against TBI.

Anatomic double-bundle anterior cruciate ligament reconstruction restores patellofemoral contact areas and pressures more closely than nonanatomic single-bundle reconstruction.

PURPOSE: To investigate the effects of anterior cruciate ligament (ACL) deficiency and nonanatomic single-bundle (SB) and anatomic double-bundle (DB) ACL reconstruction on the contact characteristics of the patellofemoral (PF) joint. METHODS: By use of a materials testing system, 7 fresh-frozen human cadaveric knees were tested. The following states were tested: ACL-intact knee, nonanatomic SB ACL reconstruction, anatomic DB ACL reconstruction, and ACL-deficient knee. Hamstring autografts were used. PF contact pressures and areas were measured with pressure-sensitive film at 30°, 60°, and 90° of knee flexion with a constant 100-N load on the quadriceps tendon. RESULTS: The total contact area of ACL-deficient and nonanatomic SB ACL-reconstructed knees (123.8 ± 63.9 and 149.6 ± 79.3 mm(2), respectively) significantly decreased when compared with those of the intact knee (206.1 ± 83.6 mm(2)) at 30° of knee flexion. The lateral-facet peak pressure of ACL-deficient and nonanatomic SB ACL-reconstructed knees (1.12 ± 0.52 and 1.22 ± 0.54 MPa, respectively) significantly decreased when compared with those of the intact knee (0.68 ± 0.38 MPa) at 90° of knee flexion. Anatomic DB ACL reconstruction restored the contact pressures and areas to values similar to those of the intact knee (no significant difference). CONCLUSIONS: ACL deficiency resulted in a significant decrease in the total and medial PF contact areas and in an increase in the lateral PF contact pressure. Anatomic DB ACL reconstruction more closely restored normal PF contact area and pressure than did nonanatomic SB ACL reconstruction. CLINICAL RELEVANCE: Our findings suggest that the changes in the PF contact area and pressures in ACL deficiency and after nonanatomic SB ACL reconstruction may be one of the causes of PF osteoarthritis or other related PF problems found at long-term follow-up. Anatomic DB ACL reconstruction may reduce the incidence of PF problems by closely restoring the contact area and pressure.

Evaluation of the tunnel placement in the anatomical double-bundle ACL reconstruction: a cadaver study.

The objective of this study was to investigate the accurate AM and PL tunnel positions in an anatomical double-bundle ACL reconstruction using human cadaver knees with an intact ACL. Fifteen fresh-frozen non-paired adult human knees with a median age of 60 were used. AM and PL bundles were identified by the difference in tension patterns. First, the center of femoral PL and AM bundles were marked with a K-wire and cut from the femoral insertion site. Next, each bundle was divided at the tibial side, and the center of each AM and PL tibial insertion was again marked with a K-wire. Tunnel placement was evaluated using a C-arm radiographic device. For the femoral side assessment, Bernard and Hertel's technique was used. For the tibial side assessment, Staubli's technique was used. After radiographic evaluations, all tibias' soft tissues were removed with a 10% NaOH solution, and tunnel placements were evaluated. In the radiographic evaluation, the center of the femoral AM tunnel was placed at 15% in a shallow-deep direction and at 26% in a high-low direction. The center of the PL bundle was found at 32% in a shallow-deep direction and 52% in a high-low direction. On the tibial side, the center of the AM tunnel was placed at 31% from the anterior edge of the tibia, and the PL tunnel at 50%. The ACL tibial footprint was placed close to the center of the tibia and was oriented sagittally. AM and PL tunnels can be placed in the ACL insertions without any coalition. The native ACL insertion site has morphological variety in both the femoral and tibial sides. This study showed, anatomically and radiologically, the AM and PL tunnel positions in an anatomical ACL reconstruction. We believe that this study will contribute to an accurate tunnel placement during ACL reconstruction surgery and provide reference data for postoperative radiographic evaluation.