Posterior Tibial Artery Blood Flow Velocity Is Increased in Patients with Plantar Heel Pain.

Background/Objectives: This study aimed to investigate the relationship between posterior tibial artery blood flow velocity and plantar heel pain (PHP). Methods: The PHP group comprised patients diagnosed with plantar fasciitis with plantar heel pain during gait, and the control group comprised healthy participants without plantar heel pain. The peak systolic velocity of the posterior tibial artery was measured using ultrasonography; it was measured three times on each side, and the mean value was calculated. Receiver operating characteristic curve analysis was performed to calculate the peak systolic velocity cutoff value for plantar heel pain. Results: 23 patients (age 58.0 ± 16.5 years; 13 males and 10 females) and 23 healthy participants (age 51.3 ± 17.3 years; 10 males and 13 females) formed the PHP and control groups, respectively. Peak systolic velocity on the affected side was significantly greater in the PHP group (44.1 ± 13.1 cm/s) than in the control group (32.7 ± 5.9 cm/s). No significant difference was observed between the left and right sides in the PHP (7.1 ± 9.8 cm/s) and control (3.7 ± 3.0 cm/s) groups. A cutoff value of 38.2 cm/s was observed on the affected side. Conclusions: We quantified the increase in posterior tibial artery blood flow velocity in patients with plantar heel pain. Peak systolic velocity measurements can aid in quantitatively evaluating these patients. This study was registered as a clinical trial (UMIN000046875) on 1 October 2021.

Safety and Effectiveness of Elotuzumab in Japanese Patients with Relapsed/Refractory Multiple Myeloma: A Post-marketing Surveillance Study.

Objective Elotuzumab plus lenalidomide and dexamethasone (ELd) was approved in Japan in 2016 for the treatment of relapsed/refractory multiple myeloma (RRMM). This post-marketing surveillance study evaluated the safety and effectiveness of ELd in RRMM patients during routine clinical practice in Japan. Methods Elotuzumab safety was assessed by evaluating adverse drug reactions (ADRs), and effectiveness was assessed primarily by the best overall response. Patients The study enrolled patients with RRMM who received ELd therapy between November 18, 2016, and June 18, 2017. The safety and effectiveness analysis sets included 831 and 755 patients, respectively. Results In the safety analysis set, patients received a median (range) of 12 (1-40) elotuzumab administrations over 108 (1-728) days of treatment. The relative dose intensity of elotuzumab was ≥90% in 74.1% of patients. ADRs and serious ADRs were reported in 41.2% and 15.2% of the patients, respectively. The most common ADR was infection (12.0%), followed by lymphocytopenia (10.1%), infusion reactions (7.5%), secondary malignancies (e.g. gastric cancer and pancreatic carcinoma), cataracts, and interstitial lung disease (0.2% each). While most patients with ADRs recovered, 71 discontinued treatment, and 14 deaths were reported. The presence of comorbidities, particularly cardiovascular disorders, significantly affected the safety. The overall response rate was 41.1%. Conclusion This all-case post-marketing surveillance study showed that ELd had an acceptable tolerability profile and promising clinical activity in Japanese patients with RRMM.

Relationship Between Anterior Knee Laxity and General Joint Laxity During the Menstrual Cycle.

BACKGROUND: Anterior cruciate ligament (ACL) injury has been reported to have a higher incidence in women than in men. PURPOSE/HYPOTHESIS: The purpose was to examine the relationship of anterior knee laxity (AKL), stiffness, and generalized joint laxity (GJL) with respect to the menstrual cycle. It was hypothesized that AKL and GJL would increase during the ovulation phase, when estrogen levels are high. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 15 female university students aged >20 years and with normal menstrual cycles were evaluated. AKL was measured as anterior tibial displacement of the femur after application of 44-, 89-, and 133-N loads to the tibia. Stiffness was calculated as Δ force/Δ displacement at loads between 44 and 89 N and between 89 and 133 N. The University of Tokyo joint laxity test was used for evaluation of GJL. The participants' menstrual cycle was divided into the early follicular, late follicular, ovulation, and luteal phases using the basal body temperature method and an ovulation kit; AKL and GJL were measured once during each phase. Participants were also stratified according to the presence or absence of genu recurvatum (GR). RESULTS: There was no significant difference in AKL, stiffness, or GJL among the menstrual phases. In the GR group, AKL values at 89 N and 133 N were significantly higher in the ovulation phase than in the early follicular phase (P = .025 and P =.018, respectively); there were no significant differences in AKL among the phases in the non-GR group. In addition, the GR group in the ovulation phase had significantly higher AKL values at 44 N, 89 N, and 133 N compared with the non-GR group (P = .013, P = .005, and P = .010, respectively). There were no significant differences in GJL among the phases in the GR or non-GR groups. CONCLUSION: Women with GR may have increased AKL in the ovulation phase when compared with the early follicular phase, which may be a risk factor for ACL injury. CLINICAL RELEVANCE: The results of this study suggest that the ovulation phase may be related to the greater incidence of ACL injuries in women.

A preliminary study exploring the change in ankle joint laxity and general joint laxity during the menstrual cycle in cis women.

BACKGROUND: The purpose of the present study was to examine the relationship between ankle joint laxity and general joint laxity (GJL) in relation to the menstrual cycle, which was divided into four phases based on basal body temperature and ovulation, assessed using an ovulation kit. METHODS: Participants were 14 female college students (21-22 years) with normal menstrual cycles (cis gender). Anterior drawer stress to a magnitude of 120 N was applied for all participants. Anterior talofibular ligament (ATFL) length was measured as the linear distance (mm) between its points of attachment on the lateral malleolus and talus using ultrasonography. Data on ATFL length from each subject were used to calculate each subject's normalized length change with anterior drawer stress (AD%). The University of Tokyo method was used for evaluation of GJL. AD% and GJL were measured once in each menstrual phase. RESULTS: There was no statistically significant difference between AD% in each phase. GJL score was significantly higher in the ovulation and luteal phases compared with the early follicular phase. AD% and GJL showed a positive correlation with each other in the ovulation phase. CONCLUSIONS: Although it is unclear whether estrogen receptors are present in the ATFL, the present study suggests that women with high GJL scores might be more sensitive to the effects of estrogen, resulting in ATFL length change in the ovulation phase.

The Effects of Differences in the Morphologies of the Ulnar Collateral Ligament and Common Tendon of the Flexor-Pronator Muscles on Elbow Valgus Braking Function: A Simulation Study.

The anterior bundle (AB) and posterior bundle (PB) of the ulnar collateral ligament and the anterior common tendon (ACT) and posterior common tendon (PCT) of the flexor-pronator muscles have an independent form and an unclear form. The purpose of this study was to clarify the effect of differences in the morphologies of the AB, PB, ACT, and PCT on the elbow valgus braking function. This investigation examined three elbows. In the classification method, the AB, PB, ACT, and PCT with independent forms constituted Group I; the AB, ACT, and PCT with independent forms and the PB with an unclear form constituted Group II; the AB, PB, ACT, and PCT with unclear forms constituted Group III. The strains were calculated by simulation during elbow flexion at valgus at 0° and 10°. At 0° valgus, Group I and Group II showed similar AB and PCT strain patterns, but Group III was different. At 10° valgus, most ligaments and tendons were taut with increasing valgus angle. The average strain patterns of all ligaments and tendons were similar for the groups. The AB, PB, ACT, and PCT may cooperate with each other to contribute to valgus braking.

The origin structure of each finger in the flexor digitorum superficialis muscle.

PURPOSE: The flexor digitorum superficialis muscle (FDS) is considered the most important of the forearm flexors for maintaining elbow valgus stability. However, the relationships between the origin structure of each finger of the FDS and the anterior oblique ligament (AOL) of the ulnar collateral ligament and the common tendon (CT) in the proximal part, and morphological features are unclear. The purpose of this study was to clarify the relationships between the origin structure of each finger of the FDS and the AOL and the CT, as well as to clarify the morphological features of the muscle belly of each finger of the FDS. METHODS: This study examined 20 elbows. The origin of each finger was examined. Muscle mass, muscle fiber bundle length, and the pennation angle of each finger were also measured. RESULTS: In all cases, the third and fourth digits originated from the radius, the anterior common tendon (ACT), and the posterior common tendon (PCT). The second and fifth digits (18 elbows) or an independent fifth digit (2 elbows) originated from the ACT, the PCT, the AOL, and other soft tissues of the elbow. Muscle mass and muscle fiber bundle length in the muscle belly of the third and fourth digits were significantly heavier and longer, respectively, than in the muscle belly of the second and fifth digits. CONCLUSION: Because the second and fifth digits or an independent fifth digit originated from the AOL, their contraction may cause tension in the AOL.

Morphological Features of the Ulnar Collateral Ligament of the Elbow and Common Tendon of Flexor-Pronator Muscles.

BACKGROUND: The anterior bundle (AB) of the ulnar collateral ligament is the most important structure for valgus stabilization of the elbow. However, anatomic relationships among the AB, posterior bundle (PB) of the ulnar collateral ligament, and common tendon (CT) of the flexor-pronator muscles have not been fully clarified. PURPOSE: To classify the AB, PB, and CT and to clarify their morphological features. STUDY DESIGN: Descriptive laboratory study. METHODS: This investigation examined 56 arms from 31 embalmed Japanese cadavers. The CT investigation examined 34 arms from 23 embalmed Japanese cadavers with CTs remaining. Type classification was performed by focusing on positional relationships with surrounding structures. Morphological features measured were length, width, thickness, and footprint for the AB and PB and attachment length, thickness, and footprint for the CT. RESULTS: The AB was classified as type I (44 elbows; 78.6%), can be separated as a single bundle, or type II (12 elbows; 21.4%), cannot be separated from the PB and joint capsule. The PB was classified as type I (28 elbows; 50.0%), can be separated as a single bundle; type IIa (6 elbows; 10.7%), posterior edge cannot be separated; type IIb (7 elbows; 12.5%), anterior edge cannot be separated; or type III (15 elbows; 26.8%), cannot be separated from the joint capsule. The CT was classified as type I (18 elbows; 52.9%), can be separated from the AB, or type II (16 elbows; 47.1%), cannot be separated from the AB. Significant differences in frequencies of AB, PB, and CT types were identified between men and women. Morphological features were measured only for type I of each structure, and reliability was almost perfect. CONCLUSION: These results suggest that the AB, PB, and CT each can be classified into an independent form and an unclear form. Presence of the unclear form was suggested as one factor contributing to morphological variation. CLINICAL RELEVANCE: This study may provide basic information for clarifying functional roles of the AB, PB, and CT.

Anatomic Characteristics of Tissues Attached to the Fifth Metatarsal Bone.

BACKGROUND: Two types of stress, bending stress and traction stress, have been reported to be involved in the mechanism of Jones fracture. However, little is known about the risk factors for traction stress. PURPOSE: To classify the attachment position of the peroneus brevis muscle (PB), peroneus tertius (PT), lateral band of the plantar aponeurosis (LB), and the long plantar ligament (LPL), focusing on the zone where a Jones fracture occurs (zone 2), and to compare the footprint area of each tissue type. STUDY DESIGN: Descriptive laboratory study. METHODS: This study examined 102 legs from 55 Japanese cadavers. Type classification was performed by focusing on the positional relationship between each tissue attachment and the zone where Jones fracture occurs (zone 2). The classifications were as follows: type I, attached proximal to the border between zones 1 and 2; type IIa, attached to the border between zones 1 and 2 with one attached part; and type IIb, attached across the border between zones 1 and 2 with two or more attached parts. The footprint areas of the PB, PT, LB, and LPL were compared between tissue types and within each attachment classification. RESULTS: The PB was recorded as type I in 41 feet (40.2%), type IIa in 56 feet (54.9%), and type IIb in 5 feet (4.9%); the PT was recorded as type IIa in 54 feet (60.0%) and type IIb in 36 feet (40.0%); and the LB was recorded as type I in 27 feet (26.5%) and type IIa in 75 feet (73.5%). The LPL did not attach to the fifth metatarsal bone. No significant difference was found in the footprint area between type I PB and type I LB. CONCLUSION: The results indicate that type I, which attaches proximal to zone 2, occurs with PB and LB, and there was no significant difference in the footprint area between them. These findings suggest that type I is involved in traction stress. In the future, biomechanical research based on the results of this study will be necessary. CLINICAL RELEVANCE: The results of this study provide basic research for investigating the mechanism of Jones fracture and the cause of delayed healing.

A new method for estimating three-dimensional movement of the patella using a surface mapping method and computed tomography.

INTRODUCTION: A previous study reported a method called the 2D-3D registration technique to examine three-dimensional movement of the patella. However, that method requires a biplane fluoroscopy system. In the present study, the aim was to establish a new method (CT-based surface mapping method) to estimate three-dimensional positions and angles of the patella with a motion capture system and CT. METHODS: In Study 1, the most appropriate parameters for the CT-based surface mapping method (i.e., target edge length, threshold of thickness of the soft tissue, and minimum distance between markers) were explored and determined. In Study 2, three-dimensional movement (i.e., positions and angles) of the patella using the CT-based surface mapping method and the most appropriate parameters were determined, and they were compared with the true positions and angles obtained by CT. RESULTS: The results of Study 1 showed that the most appropriate conditions were as follows: (1) target edge length, 3 mm; (2) threshold of thickness of the soft tissue, 0-20 mm; and (3) minimum distance between markers, 10 mm. The results of Study 2 showed that the errors of the positions and angles were less than approximately 10 mm and 10° at most, respectively (both supine and sitting positions). CONCLUSION: The CT-based surface mapping method may be useful for a future study to clarify differences in three-dimensional movements of the patella between patients with patellar tendinitis and healthy subjects.

Relationships between differences in the number of fiber bundles of the anterior talofibular ligament and differences in the angle of the calcaneofibular ligament and their effects on ankle-braking function.

PURPOSE: The aim was to clarify the relationships between differences in the number of fiber bundles of the anterior talofibular ligament (ATFL) and differences in the angle of the calcaneofibular ligament (CFL) with respect to the long axis of the fibula and their effects on ankle braking function. METHODS: The study sample included 110 Japanese cadavers. ATFLs were categorized as: Type I with one fiber bundle; Type II with two fiber bundles with incomplete separation and complete separation; and Type III with three fiber bundles. The CFLs were categorized according to the angles of the CFLs with respect to the long axis of the fibula and the number of fiber bundles. Six categories were established: CFL10° (angle of the CFL with respect to the long axis of the fibula from 10° to 19°); CFL20° (range 20°-29°); CFL30° (range 30°-39°); CFL40° (range 40°-49°); CFL50° (range 50°-59°); and CFL2 (CFLs with two crossing fiber bundles). RESULTS: ATFL was Type I in 34 legs (31%), Type II in 66 legs (60%), and Type III in 10 legs (9%). Five CFL categories were identified: CFL10° in 4 feet (3.7%); CFL20° in 23 feet (20.9%); CFL30° in 34 feet (30.9%); CFL40° in 33 feet (30%); CFL50° in 15 feet (13.6%); and CFL2 in one foot (0.9%). Type III contained mainly CFL40° and CFL50° (7 of 10 feet). CONCLUSIONS: ATFL and CFL appear to cooperate in the ankle joint braking function.

The relationships between the quadratus plantae and the flexor digitorum longus and the flexor hallucis longus.

PURPOSE: The purpose of this research was to clarify the relationships between quadratus plantae (QP) and flexor digitorum longus (FDL) and flexor hallucis longus (FHL) using large-scale specimens. METHODS: This study examined 116 legs from 62 Japanese cadavers. The QP was classified as: Type I, formed by the lateral and medial heads; Type II, the lateral head is absent; and Type III, the medial head is absent. The FHL branches to the lesser toes were classified as: Type A, connection from FHL to toe 2; Type B, connection from FHL to toes 2 and 3; Type C, connection from FHL to toes 2-4. Next, the relationships between QP and FHL and FDL were observed. RESULTS: Type I accounted for 87%, Type II for 10%, and Type III for 3%. Type A accounted for 33%, Type B for 53%, and Type C for 14%. Regarding the relationship between QP and FDL, regardless of the classification of the connections of the FHL tendon slip to the lesser toes, QP attachments to FDL branching to toes 2, 3, and 4 were seen in 47-59%. Furthermore, QP attachments to FDL branching to toes 2, 3, 4, and 5 were seen in 41-47%. CONCLUSIONS: QP appears to function strongly to counter the oblique pull of FDL and FHL and as a lesser digit plantar flexor.

Differences in the strain applied to Achilles tendon fibers when the subtalar joint is overpronated: a simulation study.

PURPOSE: The purpose of this study was to investigate the strain applied to each of the tendon fiber bundles of the medial head of the gastrocnemius (MG), the lateral head of the gastrocnemius (LG), and the soleus muscle (Sol) that compose the Achilles tendon (AT) when the subtalar joint is pronated and supinated. METHODS: Three AT twist types (least, moderate, extreme) were investigated. Using the MicroScribe system, the AT and the talocrural and subtalar joints were digitized to reconstruct three-dimensional models. Using this system, subtalar joint rotations in the pronation (20°) and supination (20°) directions were simulated, and the degrees of strain (%) on each tendon were calculated. RESULTS: For all twist types, when the subtalar joint was pronated, MG, LG, and Sol stretched, and when supinated, MG, LG, and Sol shortened. In particular, the least and severe twist types had large degrees of strain of Sol when the subtalar joint was pronated, and furthermore, each tendon fiber composing Sol had different degrees of strain. CONCLUSIONS: The study results suggest that the degree of strain applied within the AT with subtalar joint pronation is not constant, and that, especially in least and extreme twist types, the risk of developing AT disorders may increase.

The effect of differences in the number of fiber bundles of the anterior tibial ligament on ankle braking function: a simulation study.

PURPOSE: The aim was to clarify the effect of differences in the number of fiber bundles of the anterior tibial ligament (ATFL) on ankle braking function. METHODS: The study sample included 81Japanese cadavers. ATFLs were categorized as: Type I with one fiber bundle; Type II with two fiber bundles that were completely separated; and Type III with three fiber bundles. Three-dimensional reconstructions of a single specimen from each category were then created. These were used to simulate and calculate ATFL strain during dorsiflexion (20°) and plantarflexion (30°) on the talocrural joint axis and inversion (20°) on the subtalar joint axis. RESULTS: Almost all types of superior fiber lines were stretched with dorsiflexion and plantarflexion. Regardless of Type, the inferior fiber line was shortened with plantarflexion and stretched with dorsiflexion. The inferior fiber bundle of Type III was shortened only at plantarflexion 30° and inversion 20°, but in all others it was stretched. CONCLUSIONS: The results suggest that Type III was weaker than Type I and Type II in terms of ankle plantarflexion and inversion braking function.

Morphological characteristics of the lateral talocalcaneal ligament: a large-scale anatomical study.

PURPOSE: The purpose of this study is to clarify the morphological characteristics of the lateral talocalcaneal ligament (LTCL). METHODS: This study examined 100 legs from 54 Japanese cadavers. The LTCL was classified into three types: Type I, the LTCL branches from the calcaneofibular ligament (CFL); Type II, the LTCL is independent of the CFL and runs parallel to the calcaneus; and Type III, the LTCL is absent. The morphological features measured were fiber bundle length, fiber bundle width, and fiber bundle thickness. RESULTS: The LTCL was classified as Type I in 18 feet (18%), Type II in 24 feet (24%), and Type III in 58 feet (58%). All LTCLs were associated with the anterior talofibular ligament at the talus. There was no significant difference in morphological characteristics by Type for each ligament. CONCLUSIONS: The LTCL was similar to the CFL in terms of fiber bundle width and fiber bundle thickness.

Design, synthesis and X-ray crystallographic study of new nonsecosteroidal vitamin D receptor ligands.

We designed and synthesized nonsecosteroidal vitamin D receptor (VDR) ligands that formed H-bonds with six amino acid residues (Tyr143, Ser233, Arg270, Ser274, His301 and His393) of the VDR ligand-binding domain. The ligand YR335 exhibited potent transcriptional activity, which was comparable to those of 1α,25-dihydroxyvitamin D(3) and YR301. The crystal structure of the complex formed between YR335 and the VDR ligand-binding domain was solved, which revealed that YR335 formed H-bonds with the six amino acid residues mentioned above.