A lactate-induced response to hypoxia.

Organisms must be able to respond to low oxygen in a number of homeostatic and pathological contexts. Regulation of hypoxic responses via the hypoxia-inducible factor (HIF) is well established, but evidence indicates that other, HIF-independent mechanisms are also involved. Here, we report a hypoxic response that depends on the accumulation of lactate, a metabolite whose production increases in hypoxic conditions. We find that the NDRG3 protein is degraded in a PHD2/VHL-dependent manner in normoxia but is protected from destruction by binding to lactate that accumulates under hypoxia. The stabilized NDRG3 protein binds c-Raf to mediate hypoxia-induced activation of Raf-ERK pathway, promoting angiogenesis and cell growth. Inhibiting cellular lactate production abolishes the NDRG3-mediated hypoxia responses. Our study, therefore, elucidates the molecular basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases.

How is eyeball growth associated with optic nerve head shape and glaucoma? The Lamina cribrosa/Bruch's membrane opening offset theory.

The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma.

Comparison of current relative value unit-based prices and utility between common surgical procedures, including orthopedic surgeries, in South Korea.

BACKGROUND: The medical pricing system strongly influences physicians' job satisfaction and patient health outcomes. This study aimed to investigate the current relative value unit (RVU)-based pricing and utility of patients in commonly performed surgical procedures in South Korea. METHODS: Fifteen common surgical procedures were selected from OECD statistics, and three additional orthopedic procedures were examined. The current pricing of each surgical procedure was retrieved from the Korea National Health Insurance Service, and the corresponding utilities were obtained as quality-adjusted life year (QALY) gains from previous studies. The relationship between the current prices (RVUs) and the patients' utility (incremental QALY gains/year) was analyzed. Subgroup analysis was performed between fatal and non-fatal procedures and between orthopedic and non-orthopedic procedures. RESULTS: A significant negative correlation (r = - 0.558, p < 0.001) was observed between RVU and incremental QALY among all 18 procedures. The fatal subgroup had a significantly higher RVU than the non-fatal subgroup (p < 0.05), while the former had a significantly lower incremental QALY than the latter (p < 0.001). Orthopedic procedures showed higher incremental QALY values than non-orthopedic procedures, but they did not show higher prices (RVU). CONCLUSIONS: This paradoxical relationship between current prices and patient utility is attributed to the higher pricing of surgical procedures for fatal and urgent conditions. Orthopedic surgery has been found to be a cost-effective treatment strategy. These findings could contribute to a better understanding of the potential role of incremental QALY in pursuing value-based purchasing or reasonable modification of the current medical fee schedule.

Natural course of talar avascular necrosis during short-term follow-up and factors associated with Disease progression.

BACKGROUND: This retrospective cohort study aimed to investigate the natural history of talar avascular necrosis (AVN) during short-term outpatient follow-up and to identify the risk factors for progression to collapse and arthritic changes. METHODS: Thirty-four cases of talar AVN from 34 patients (15 males, 19 females) were included. The mean age of the patients was 48.9 years (SD 16.0 years) and the mean follow-up period was 39.5 months (SD 42.0 months). The patients were divided into two groups i.e., progression and non-progression groups. The progression group consisted of those who showed aggravation of the Ficat stage during the follow-up period or advanced arthritis of the ankle joint (Ficat stage 4) at presentation. Demographic data and information regarding BMI, medical comorbidities, trauma history, bilaterality, and location of the lesion (shoulder vs. non-shoulder lesions) were collected. Following the univariate analysis, a binary logistic regression analysis was performed. RESULTS: The location of the talar AVN was the only significant factor (p = 0.047) associated with disease progression. A total of 14.3% (2 of 14) of the central (non-shoulder) talar AVN lesions showed progression, while 50% (10 of 20) of shoulder lesions aggravated during follow-up. Age, sex, bilaterality, medical comorbidities, and trauma history were not associated with progressive talar collapse or subsequent arthritic changes in talar AVN. CONCLUSIONS: Conservative treatment should be considered for a central lesion of the talar AVN because it tends to remain stable without progression. A more comprehensive study with a larger study population is required to establish the surgical indications for talar AVN. LEVEL OF EVIDENCE: Prognostic level III.

Postoperative Stability in Displaced Ankle Fractures With Concomitant Ligamentous Injuries.

Ankle instability, which can be attributed to either the deltoid or lateral ligamentous complex, may be both a cause and a consequence of ankle fractures. This study aimed to assess postoperative ankle instability in patients with displaced ankle fractures. A total of 54 patients with displaced ankle fractures were included. Malleolar fractures were surgically reduced and fixated, and if necessary, the syndesmosis was stabilized. Concomitant deltoid injuries were left unrepaired. Ankle stress radiographs were taken approximately 25.4 months after surgery, with a standard deviation of 20.5 months. Radiographic measurements included the tibiotalar tilt angle (TT) on varus stress view, anterior translation of the talus (AT) on the anterior drawer view, and the medial clear space (MC) and tibiotalar tilt angle on the valgus stress view. These measurements were compared between the injured and the noninjured contralateral ankle for all patients as well as in a subgroup of 19 patients with concomitant deltoid and syndesmosis injuries. There were no significant differences in Varus TT (p = .675, p = .394), AT (p = .516, p = .967), Valgus MC (p = .190, p = 0.498), and Valgus TT (p = .173, p = .442) between the injured and noninjured ankles in the whole group of patients as well as in the subgroup of patients with concomitant deltoid and syndesmosis injuries. Patients with displaced ankle fractures exhibited radiographically stable ankles postoperatively. Syndesmosis fixation without deltoid ligament repair is a viable treatment option for achieving ankle stability postoperatively in fractures with both ligament injuries.

Radiographic Measurements Associated With Ankle Power Generation During Gait in Patients With Cerebral Palsy.

BACKGROUND: Pes planovalgus (PV) deformity accounts for lever arm dysfunction and compromises gait in patients with cerebral palsy (CP). However, the association between ankle power generation and radiographic indices is not yet understood. We aimed to investigate the association between ankle power and radiographic indices during gait in patients with CP concomitant with PV deformity. METHODS: Patients older than 14 years with ambulatory CP and PV deformity were included. All the patients underwent 3-dimensional gait analysis and weight-bearing foot radiography. Gait data were collected, including foot progression angle, tibial rotation, hip rotation, and ankle power generation. Radiographic measurements included anteroposterior (AP) talo-first metatarsal angle, lateral talo-first metatarsal angle, and hindfoot angle. A linear mixed-effects model was performed to identify significant radiographic indices associated with ankle power generation. RESULTS: Thirty-one limbs from 15 patients with spastic diplegia and 6 with spastic hemiplegia were included. Statistical analysis demonstrated that ankle power generation was significantly correlated with the CP type ( P =0.0068) and AP talo-1 st metatarsal angle ( P =0.0230). CONCLUSION: Ankle power generation was significantly associated with the AP talo-first metatarsal angle. Surgeons might need to pay attention to correcting forefoot abduction to restore ankle power when planning surgeries for pes PV deformities in patients with CP. LEVEL OF EVIDENCE: Prognostic Level III.

Intrasubject Radiographic Progression of Hallux Valgus Deformity in Patients With and Without Metatarsus Adductus: Bilateral Asymmetric Hallux Valgus Deformity.

This study was to analyze intrasubject radiographic progression of the hallux valgus deformity by comparing the mildly and severely affected sides in patients with bilateral asymmetric hallux valgus in the whole group as well as the metatarsus adductus and the nonmetatarsus adductus subgroups. A total of 186 patients with bilateral asymmetrical hallux valgus deformity with a difference of 5° or greater in the hallux valgus angle were included, and 11 radiographic measurements were analyzed. The radiographic differences between the mildly and severely affected sides were compared. Correlation between the changes in the hallux valgus angle and those in other measurements was analyzed, and multiple regression analyses were performed. The anteroposterior talo-second metatarsal angle showed no significant difference between the mildly and severely affected sides. Changes in the intermetatarsal angle and sesamoid rotation angle were significantly associated with the progression of hallux valgus angle in the whole group as well as the nonmetatarsus adductus subgroup. Change in the intermetatarsal angle (p = .006) was the significant factor associated with the progression of hallux valgus angle in the metatarsus adductus subgroup. The anteroposterior talo-second metatarsal angle might be useful in evaluating the overall foot shape in the hallux valgus deformity. Progression of the hallux valgus deformity might be pathophysiologically different between those with and without metatarsus adductus.

Relationship between Three-Dimensional Magnetic Resonance Imaging Eyeball Shape and Optic Nerve Head Morphology.

PURPOSE: To determine if the 3-dimensional (3D) eyeball shape is associated with the positions of the central retinal vascular trunk (CRVT) and the externally oblique border (EOB) in the optic nerve head (ONH). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Fifty-six subjects (112 eyes) with a diagnosis of glaucoma or glaucoma suspect. METHODS: The eyeball shape on 3D magnetic resonance imaging (MRI) scans was classified according to the dimension of the longest diameter: axial dimension (prolate sphere), group 1; horizontal dimension (horizontally oblate sphere), group 2; and vertical dimension (vertically oblate sphere), group 3. The deviation of the CRVT, as a surrogate of lamina cribrosa (LC) shift, was measured from the center of the Bruch's membrane opening (BMO) demarcated by OCT imaging, with the horizontal midline as 0° and the superior location as a positive value. The angular location of the longest EOB was also measured. MAIN OUTCOME MEASURE: Positions of CRVT and EOB according to the 3D eyeball shape. RESULTS: Among 112 eyes, 54 (48%) had a prolate shape (group 1), 23 (21%) had a horizontally oblate shape (group 2), and 35 (31%) had a vertically oblate shape (group 3). The angular deviation of the CRVT differed among the groups: to the nasal side in group 1, to the temporal side in group 2, and along the vertical meridian in group 3. In cases of asymmetric eyeball shape, the CRVT was deviated toward the undergrown side from the overgrown side, regardless of grouping. The angular location of the longest EOB was in the direction opposite to the CRVT position (P < 0.001). A generalized estimating equation analysis revealed that the temporal location of the CRVT was associated with older age (P = 0.001), nasal location of the longest EOB (P < 0.001), and oblate shape of the eyeball (P < 0.001, group 2; P = 0.007, group 3). CONCLUSIONS: The position of the CRVT and EOB were associated with the 3D eyeball shape. Considering that infant ONH morphology is highly uniform, various modes of eyeball expansion during growth can result in diverse directionalities of offset between the LC and the BMO in adults.

Evaluation of factors affecting external tibial torsion in patients with cerebral palsy.

BACKGROUND: Gait deviation and associated torsional problems are common in patients with cerebral palsy (CP). Although femoral anteversion in CP has been extensively reviewed in previous studies, only a few studies have focused on tibial torsion. Therefore, this study aimed to evaluate tibial torsion in patients with CP and investigate the affecting factors. METHODS: Consecutive patients with cerebral palsy who underwent 3-dimensional computed tomography for the assessment of rotational profiles were reviewed. Femoral anteversion and tibial torsion were measured, and the demographic characteristics of the patients were recorded. A linear mixed model was implemented to overcome the retrospective nature of the study. RESULTS: After the implementation of inclusion and exclusion criteria, 472 patients were enrolled for this study. With age, external tibial torsion increased, while femoral anteversion decreased. The factors affecting external tibial torsion were increased femoral anteversion (p = 0.0057), increased age (p < 0.0001), higher Gross Motor Function Classification System (GMFCS) level (p < 0.0001), and involved/uninvolved limbs of hemiplegia (p = 0.0471/p = 0.0047). CONCLUSIONS: Older age, GMFCS level IV/V, hemiplegia, and increased femoral anteversion were the independent risk factors of increased external tibial torsion; therefore, performing an imaging study is recommended for assessing the extent of tibial torsion in patients with such characteristics.

Leg length discrepancy, overgrowth, and associated risk factors after a pediatric tibial shaft fracture.

BACKGROUND: This study was performed to investigate leg length discrepancy (LLD), overgrowth, and associated risk factors after pediatric tibial shaft fractures. MATERIALS AND METHODS: This study included 103 patients younger than 14 years of age (mean age 7.1 years; 75 boys, 28 girls) with unilateral tibial shaft fracture and a minimum follow-up of 24 months. LLD was calculated as the difference between the lengths of the injured and uninjured limbs. Overgrowth was calculated by adding the fracture site shortening from the LLD. Risk factors were assessed in patients with LLD < 1 cm and ≥ 1 cm and overgrowth < 1 cm and ≥ 1 cm. RESULTS: Casting and titanium elastic nailing (TEN) were performed on 64 and 39 patients, respectively. The mean LLD and overgrowth were 5.6 and 6.4 mm, respectively. There were significant differences in sex (p = 0.018), age (p = 0.041), fibular involvement (p = 0.005), injury mechanism (p = 0.006), and treatment methods (p < 0.001) between patients with LLDs < 1 cm and ≥ 1 cm. There were significant differences in sex (p = 0.029), fibular involvement (p = 0.002), injury mechanism (p = 0.008), and treatment methods (p < 0.001) between patients with overgrowth < 1 cm and ≥ 1 cm. Sex and treatment methods were risk factors associated with LLD ≥ 1 cm and overgrowth ≥ 1 cm following pediatric tibial shaft fracture. The boys had a 7.4-fold higher risk of LLD ≥ 1 cm and 5.4-fold higher risk of overgrowth ≥ 1 cm than the girls. Patients who underwent TEN had a 4.3-fold higher risk of LLD ≥ 1 cm and 4.8-fold higher risk of overgrowth ≥ 1 cm than those treated by casting. CONCLUSIONS: Patients undergoing TEN showed greater LLD and overgrowth than those undergoing casting, with boys showing greater LLD and overgrowth than girls. Surgeons should consider the possibility of LLD and overgrowth after pediatric tibial shaft fractures, especially when performing TEN for boys. LEVEL OF EVIDENCE: Level III.

Transcultural adaptation and validation of a Korean version of the Oxford Ankle Foot Questionnaire for children.

BACKGROUND: The purpose of this study was to translate and transculturally adapt the original English version of the Oxford Ankle Foot Questionnaire (OAFQ) into a Korean version, and to evaluate its psychometric properties. METHODS: A Korean OAFQ for children was developed according to established guidelines. To test validity, 169 consecutive patients with foot and ankle problems and their caregivers each completed the OAFQ. The children also completed a Korean version of the KIDSCREEN-52 health related quality of life questionnaire (KIDSCREEN-52 HRQOL). To validate the Korean version of the OAFQ, reliability (child-parent agreement and internal consistency), feasibility (floor and ceiling effects), and construct validity were evaluated, and factor analysis was performed. RESULTS: In terms of reliability, Cronbach's α values were > 0.7 in all subscales of the OAFQ (0.765 to 0.901). Child-parent agreement was confirmed by high intraclass correlation coefficients for all subscales (0.791 to 0.863). In terms of construct validity, there were moderate correlations between the subscales of the OAFQ and the subscales of the KIDSCREEN-52 HRQOL. Factor analysis revealed a three-component solution for both the child/adolescent and parent-proxy version, by combining the school and play, and footwear items into one subscale. In terms of feasibility, no floor effects were found for all subscales. However, ceiling effects were observed for the school and play, and emotional subscales for child/adolescent and parent-proxy versions. CONCLUSIONS: The OAFQ was successfully translated and transculturally adapted into the Korean language; the Korean version of the OAFQ represents a reliable and valid instrument for evaluating children's foot or ankle problems. However, factor analysis suggested the use of a three-subscale questionnaire.

Case report: what gives the myopic tilted disc an oval appearance?

BACKGROUND: Myopic tilted disc, observed as an oval disc, has been alleged to be a funduscopic en-face manifestation of excessive optic nerve head (ONH) sloping or tilting. Here, we report the case of a myopic child showing a developing oval disc in fundus photos during axial elongation, but without progressive tilting in spectral-domain optical coherence tomography (SD-OCT) images. CASE PRESENTATION: By merging B-scan SD-OCT images of the ONH and macula, the curvature of the posterior pole, including both the fovea and ONH, was reconstructed and compared before and after 2 years of axial elongation. Despite the marked increase of disc ovality, the posterior polar curvature was rarely changed. The preponderance of optic disc change was induced by the shift of the temporal disc margin in the nasal direction. This shifting alone imitated an increase of tilt angle but one that was still far smaller than the required degree of tilt for ONH-tilt-based disc ovality. To clarify, we calculated the required extent of axial elongation to obtain a substantial degree of ONH tilt when considering the adjacency of the fovea and the ONH. Without a focal increase of posterior polar curvature, which is to say posterior staphyloma, such change is not possible until the axial length increases extraordinarily. CONCLUSION: The most prominent change in the development of myopic tilted disc, which change gives it an oval appearance and imitates a tilt when measured, is actually not a tilt but rather a shift of the temporal disc margin.

Progression of planovalgus deformity in patients with cerebral palsy.

BACKGROUND: Analyzing radiographic changes of pes planovalgus(PV) deformity of cerebral palsy(CP) patients according to age and influencing factors. METHODS: CP patients with PV deformity younger than 18 years old who had undergone more than a year of follow-up with at least two standing foot radiographs were included. Anteroposterior and lateral talo-first metatarsal(talo-1stMT), talo-second metatarsal(talo-2ndMT), and hallux valgus(HV) angles were measured on the radiographs. The rate of progression was adjusted by multiple factors using the linear mixed model, with the Gross Motor Function Classification System(GMFCS) level as the fixed effect and age and each subject as random effects. RESULTS: Overall, 194 patients were enrolled in this study, and 1272 standing foot radiographs were evaluated. The AP talo-2ndMT angle progressed by 0.59° (p < 0.0001) and 0.64° (p = 0.0007) in GMFCS level II and III patients, respectively; however, there was no significant change in GMFCS level I patients (p = 0.3269). HV was significantly affected by age in all three GMFCS groups; it increased by 0.48° (p < 0.0001), 0.66° (p < 0.0001), and 1.19° (p < 0.0001) for levels I, II, and III, respectively. The lateral talo-1stMT angle showed improvements in GMFCS level I and II patients (0.43°, p < 0.0001, and 0.61°, p < 0.0001, respectively). In GMFCS level III patients, there was no significant improvement in the lateral talo-1stMT angle (p = 0.0535). CONCLUSIONS: The GMFCS level was the single most important factor influencing the progression of radiographic indices in PV deformity in CP. The AP talo-1stMT and talo-2ndMT angles progressed in patients with GMFCS levels II and III. Physicians should take this result into consideration when planning the timing of the surgery. LEVEL OF EVIDENCE: Prognostic Level IV.

Discrepancy between true ankle dorsiflexion and gait kinematics and its association with severity of planovalgus foot deformity.

BACKGROUND: In planovalgus deformity with triceps contracture, a midfoot break happens, and ankle dorsiflexion (ADF) occurs at the mid-tarsal joint during gait. Results of standard 3D gait analysis may misinterpret the true ankle dorsiflexion because it recognizes the entire foot as a single rigid segment. We performed this study to investigate whether the severity of planovalgus deformity is associated with the discrepancy between the value of ADF evaluated by physical examination and 3-dimensional (3D) gait analysis. In addition, we aimed to identify the radiographic parameters associated with this discrepancy and their relationships. METHODS: Consecutive 40 patients with 65 limbs (mean age, 11.7 ± 5.5 years) with planovalgus foot deformity and triceps surae contracture were included. All patients underwent 3D gait analysis, and weightbearing anteroposterior (AP) and lateral (LAT) foot radiographs. ADF with knee extension was measured using a goniometer with the patient's foot in an inverted position. RESULTS: Twenty-one limbs underwent operation for planovalgus foot deformity, and 56 limbs underwent operation for equinus deformity. The difference between ADF on physical examination and ADF at initial contact on gait analysis was 17.5 ± 8.4°. Differences between ADF on physical examination and ADF at initial contact on gait analysis were significantly associated with the LAT talus-first metatarsal angle (p = 0.008) and calcaneal pitch angle (p = 0.006), but not associated with the AP talus-first metatarsal angle (p = 0.113), talonavicular coverage angle (p = 0.190), talocalcaneal angle (p = 0.946), and naviculocuboid overlap (p = 0.136). CONCLUSION: The discrepancy between ADF on physical examination and 3D gait analysis was associated with the severity of planovalgus deformity, which was evaluated on weightbearing LAT foot radiographs. Therefore, physicians should be cautious about interpreting results from 3D gait analysis and perform a careful physical examination to assess the degree of equinus deformity in patients with planovalgus foot deformity.

Aggravation of Ankle Varus Incongruency Following Total Knee Replacement Correcting ≥10° of Genu Varum Deformity: A Radiographic Assessment.

BACKGROUND: This study aimed to investigate the change in ankle varus incongruencies following total knee replacement (TKR) in patients with preoperative genu varum deformity of ≥10°. METHODS: The study cohort was composed of patients who underwent TKR in a single institution for knee osteoarthritis with preoperative genu varum deformity of ≥10° and concomitant varus ankle incongruencies. Eight radiographic measurements were evaluated preoperatively and postoperatively: mechanical tibiofemoral angle, mechanical lateral distal femoral angle, medial proximal tibial angle, lateral distal tibial angle, tibial plafond inclination, talar inclination, tibiotalar tilt angle (TTTA), and tibia-mechanical axis angle. Of these, TTTA represented the quantitative degree of ankle joint incongruency. RESULTS: A total of 110 patients (male = 2; female = 108) were included in the analysis. The mean patient age was 68.9 (standard deviation [SD] 7.2) years at the time of TKR. All radiographic measurements showed significant changes postoperatively, representing the appropriate correction of genu varum deformity and restoration of the mechanical axis. Nineteen patients (17.3%) showed postoperative decrease in TTTA, 2 (1.8%) remained the same, and 89 (80.9%) showed increase. Overall, mean preoperative and postoperative TTTA were 3.3° (SD 2.2°) and 4.7° (SD 2.9°), respectively (P < .001), representing the aggravation of varus ankle incongruencies. CONCLUSION: Varus ankle incongruencies showed aggravation following TKR despite correction of genu varum deformity and restoration of the mechanical axis. This could be an important cause of postoperative increase or development of ankle pain following TKR. Therefore, patients with preoperative varus ankle incongruencies need to be warned of possible aggravation of ankle symptoms and be evaluated before TKR. LEVEL OF EVIDENCE: Prognostic level III.

Radiographic changes of the mid-tarsal joint after calcaneal lengthening for planovalgus foot deformity.

BACKGROUND: This study evaluate the radiographic changes in the mid-tarsal joint, including the calcaneocuboid and talonavicular (TN) joints after calcaneal lengthening for planovalgus deformity in children. METHODS: This study included 38 patients (68 feet) who underwent calcaneal lengthening for planovalgus deformity. Radiographic osteoarthritic changes at the CC or TN joint were defined as modified Kellgren-Lawrence grade of ≥1. RESULTS: Among the 68 feet, 31 feet (45.6%) showed radiographic osteoarthritic changes at the CC joint and 20 (29.4%) showed changes at the TN joint. Risk of radiographic osteoarthritic changes at the CC joint was associated with increased age at surgery (OR = 1.2, p = 0.038). Risk of radiographic osteoarthritic changes at the TN joint was associated with increased age at surgery (OR = 2.2; p = 0.002), preoperative AP talus-1st metatarsal angle (OR = 1.1; p = 0.044), and degree of CC subluxation (OR = 2.1; p = 0.007). CONCLUSIONS: Surgeons should consider the risk factors in the surgical correction of planovalgus deformity to prevent mid-tarsal arthritis.

Pharmacokinetic and pharmacodynamic study of lenograstim for hematopoietic stem cell mobilization: a prospective randomized study for optimal apheresis.

BACKGROUND: This study evaluated the correlation between the pharmacokinetics and pharmacodynamics of granulocyte colony-stimulating factor (lenograstim) and the impact of initiation time of apheresis on stem cell mobilization in patients with multiple myeloma. STUDY DESIGN AND METHODS: Twenty-four patients with multiple myeloma were randomized into one of the two groups (early vs. late). Lenograstim at 10 µg/kg/day once daily was injected for at least 4 consecutive days. Apheresis was initiated 2 hours after the fourth dose of lenograstim in the early collection group and 16 hours after the fourth dose of lenograstim in the late collection group. Blood sampling for pharmacokinetics was performed within 30 minutes before, and 1, 2, 6, and 24 hours after the fourth dose of lenograstim. RESULTS: Overall, the two groups (early vs. late, n = 10 vs. 14) exhibited similar baseline characteristics including age, sex, subtype of myeloma, stage distribution, and myeloma-associated symptoms. No correlation was found between plasma lenograstim concentration and peripheral blood (PB) CD34+ cell counts or hematopoietic progenitor cells. In the late collection group, the median number of apheresis procedures for minimal collection was significantly lower (early vs. late: 2 vs. 1; p = 0.04) and there was a higher number of total collected PB CD34+ cells in a single session of apheresis (1.4 vs. 3.1; p = 0.06). There were no differences in median overall PB stem cell collection efficiency. CONCLUSION: Late collection positively impacted the number of apheresis procedures for minimal collection, with numerically improved PB stem cell collection efficiency at first apheresis in patients with multiple myeloma.

Effects of soft tissue surgery on transverse kinematics in patients with cerebral palsy.

BACKGROUND: Gait disturbances, including flexed knee gait, stiff knee gait, and tip-toeing gait, are common in patients with cerebral palsy (CP). There has been no reports regarding kinematic changes in the transverse plane after soft tissue surgeries, such as distal hamstring lengthening (DHL), rectus femoris transfer (RFT), and tendo-Achilles lengthening (TAL). This study aimed to evaluate changes in the transverse plane after soft tissue surgery in patients with CP by assessing the effects of the DHL, RFT, and TAL. METHODS: The study enrolled 156 consecutive patients (mean age, 8.4 years; range, 4.4 to 20.9), representing 213 operated limbs, who underwent soft tissue surgery including DHL with semitendinosus transfer, RFT, and TAL. All patients were assessed by preoperative and 1-year postoperative three-dimensional gait analysis. Changes in transverse plane kinematics after soft tissue surgery and affecting factors were analyzed. RESULTS: Sagittal kinematics including knee flexion at initial contact, ankle dorsiflexion at initial contact, and mean ankle dorsiflexion in the stance phase were significantly improved after single event multilevel surgery (all p < 0.001). Transverse kinematics, including mean tibial rotation and foot progression angle, were significantly improved to a more external angle after soft tissue surgeries (- 2.9°, p = 0.004 and - 9.5°, p < 0.001). The mean hip rotation was significantly improved to a more external angle by RFT (- 4.7°, p = 0.010) and the foot progression angle was significantly improved to a more external angle by TAL (- 3.9°, p = 0.028). CONCLUSIONS: This study found that the transverse kinematics were improved to a more external angle after soft tissue surgery in patients with CP. Therefore, clinicians should consider that soft tissue surgery can affect the transverse plane kinematics in patients with CP. To confirm our findings, further research regarding the natural history of femoral and tibial torsion in children with CP is needed.

Foot and Ankle Radiographic Parameters in Korean Adults Vary by Sex and Age.

Although many radiographic measurements of the foot and ankle have been used, reference values for normal functional groups are rarely reported. These can change according to sex and age; therefore, this study aimed to: (1) determine reference values for radiographic foot and ankle angles in an asymptomatic healthy Korean population, and (2) compare differences in the measurements according to sex and age. A total of 200 healthy volunteers were recruited, including 100 young adults (50 males, 50 females) aged 20 to 35 years, and 100 older adults (50 males, 50 females) aged 60 to 69 years. Weightbearing ankle anteroposterior views, talar tilt, and tibiotalar angles were measured. On the weightbearing foot anteroposterior views, the hallux valgus, hallux interphalangeal, and talo-first metatarsal angles were measured. On the weightbearing lateral foot views, the calcaneal pitch, lateral talo-calcaneal, lateral talo-first metatarsal, and lateral calcaneo-first metatarsal angles were measured. Values were stratified by sex and age, and statistically compared. The hallux valgus, calcaneal pitch, and lateral calcaneo-first metatarsal angles were affected by both sex and age; the hallux interphalangeal angle was affected by age and the lateral talo-first metatarsal angle by sex. We presented reference values for foot and ankle radiographic measurements in a healthy Korean population; several radiographic indices varied significantly by sex or age, which were grossly similar to previous studies based on white race. The study data can serve as a basis for evaluation of foot and ankle disorders.

Natural progression of radiographic indices in juvenile hallux valgus deformity.

BACKGROUND: This study aimed to estimate the annual change in radiographic indices for juvenile hallux valgus (JHV) and to analyze the factors that influence deformity progression. METHODS: Patients aged <15 years who had JHV and were followed up for at least 1 year were included. Hallux valgus angle (HVA), hallux interphalangeal angle, intermetatarsal angle, metatarsus adductus angle, distal metatarsal articular angle, anteroposterior talo-first metatarsal angle, and lateral talo-first metatarsal angle were evaluated. The progression rate of HVA was adjusted by multiple factors by using a linear mixed model. RESULTS: A total of 133 feet were included. The HVA and distal metatarsal articular angle both increased by 0.8° per year (p<0.001 and p=0.003, respectively). HVA increased by 1.5° per year (p<0.001) at under the age of 10, and the HVA progression in the older patients was not statistically significant. CONCLUSIONS: JHV deformity could progress with aging. Most deformity progression could occur before the age of 10 years.