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The purpose of our research is to develop functional additives that enhance mucosal absorption of biologics, such as peptide/protein and antibody drugs, to provide their non-to-poor invasive dosage forms self-managed by patients. Our previous in vivo and in vitro studies demonstrated that the intranasal absorption of biologics in mice was significantly improved when coadministered with oligoarginines anchored chemically to hyaluronic acid via a glycine spacer, presumably through syndecan-4-mediated macropinocytosis under activation by oligoarginines. The present mouse experiments first revealed that diglycine-L-tetraarginine-linked hyaluronic acid significantly enhanced the intranasal absorption of sulpiride, which is a poor-absorptive organic compound with a low molecular weight. However, similar enhancement was not observed for levofloxacin, which has a similarly low molecular weight but is a well-absorptive organic compound, probably because its absorption was mostly dominated by passive diffusion. The subsequent monkey experiments revealed that there was no species difference in the absorption-enhancing ability of diglycine-L-tetraarginine-linked hyaluronic acid for not only organic compounds but also biologics. This was presumably because the expression levels of endocytosis-associated membrane proteins on the nasal mucosa in monkeys were almost equivalent to those in mice, and poorly membrane-permeable/membrane-impermeable drugs were mainly absorbed via syndecan-4-mediated macropinocytosis, regardless of animal species. Drug concentrations in the brain assessed in mice and monkeys and those in the cerebral spinal fluids (CSFs) assessed in monkeys indicated that drugs would be delivered from the systemic circulation to the central nervous system by crossing the blood-brain and the blood-CSF barriers under coadministration with the hyaluronic acid derivative. In line with our original hypothesis, this new set of data supported that our oligoarginine-linked hyaluronic acid would locally perform on the mucosal surface and enhance the membrane permeation of drugs under its colocalization.
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Ácido Hialurónico , Animales , Ácido Hialurónico/química , Ratones , Masculino , Administración Intranasal , Mucosa Nasal/metabolismo , Mucosa Nasal/efectos de los fármacos , Macaca fascicularis , Absorción Nasal/efectos de los fármacos , Arginina/químicaRESUMEN
PURPOSE: To evaluate bone mineral density (BMD) and radiographic and clinical outcomes of patients with varus knee osteoarthritis treated with open wedge high tibial osteotomy (OWHTO). We hypothesised that medial condyle BMD would decrease and lateral condyle BMD would increase after OWHTO. METHODS: Overall, 51 patients (mean age: 65.3 years; female: 40, male: 11) treated with OWHTO were prospectively enrolled. Several angles using whole single-leg radiographs were measured preoperatively and up to 24 months postoperatively. Five square tibial regions of interest (ROI) located below the proximal tibia as T1-T5 from medial to lateral regions and two square femoral ROI as F1 and F2 from medial and lateral regions, respectively, were defined. M/L BMD ratio was used to define the medial-to-lateral condyle BMD ratio. Femoral condyle BMD (F1 and F2) around the knee, as well as lumbar spine, and ipsilateral and contralateral femoral neck BMD, were measured before OWHTO and 3, 6, 12 and 24 months after OWHTO using dual-energy X-ray absorptiometry. Furthermore, tibial condyle BMD (T1-T5) around the knee was measured before and 24 months after OWHTO. Clinical outcomes were evaluated using the Knee Society knee and function scores, the Knee Injury and Osteoarthritis Outcome Score, and the Lysholm score preoperatively and 24 months postoperatively. A power analysis was performed. RESULTS: F1 BMD decreased by 19.2% from before to 3 months postoperatively. F2 BMD did not change up to 24 months after OWHTO. Femoral M/L BMD ratio decreased by 22.2% 3 months after OWHTO. T1 BMD and tibial M/L BMD ratio decreased, whilst T3, T4 and T5 BMD increased 24 months after OWHTO. Mean hip-knee-ankle angle (HKA) and weight-bearing line ratio were corrected from - 6.8° to 4.5° and 14.7 to 60.7%, respectively, postoperatively. Lumbar spine BMD did not change up to 12 months postoperatively. Ipsilateral femoral neck BMD decreased up to 6 months after OWHTO. CONCLUSION: Medial femoral condyle BMD decreased rapidly within 3 months and continued to decrease up to 12 months, but lateral femoral condyle BMD did not change after OWHTO. BMD measurements around the knee condyle enabled the evaluation of the changes in stress distribution before and after OWHTO with accelerated rehabilitation. LEVEL OF EVIDENCE: II.
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PURPOSE: To compare radiographic, clinical, and arthroscopic findings in patellofemoral (PF) osteoarthritis (OA) between open wedge high tibial osteotomy (OWHTO) and double-level osteotomy (DLO) with the same operative indication. METHODS: After adjustment for patient age, and coronal alignment, 36 knees with OWHTO alone and 36 knees with DLO were compared. Radiographic, clinical, and arthroscopic findings were documented before osteotomy. Arthroscopic findings were observed 1 year after osteotomy, and clinical and radiographic findings were observed 2 years after osteotomy. Patellar height was evaluated using the Insall-Salvati (IS) ratio, Carton-Deschamps (CD) index, and Blackburne-Peel (BP) index. Lateral patellar tilt and patellar shift were measured. A power analysis was performed. RESULTS: The postoperative CD and BP indices in the OWHTO group were lower than those in the DLO group (p < 0.001 and p = 0.001, respectively). The CD and BP indices in both groups significantly decreased postoperatively (all p < 0.001). Tilting angles in the OWHTO and DLO groups significantly decreased postoperatively (p < 0.001 and p = 0.002, respectively). There were no significant differences in American Knee Society scores, Kujala score, and the Knee Injury and Osteoarthritis Outcome Scores between both groups. The PF OA progression of the trochlear in the OWHTO group was higher than that in the DLO group (p = 0.002), and the PF OA progression of the patellar facet in the DLO group and anterior femoral condyle in both groups on the lateral side were higher than those on the medial side (p = 0.006, 0.032, and 0.041, respectively). CONCLUSIONS: DLO decreased the rate of low patellar height compared with OWHTO. DLO decreased the rate of PF OA progression in the trochlea compared with OWHTO. There were no significant differences in clinical outcomes in both groups. LEVEL OF EVIDENCE: Level III, case-control study.
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Enfermedades Óseas , Osteoartritis de la Rodilla , Articulación Patelofemoral , Humanos , Estudios de Casos y Controles , Articulación Patelofemoral/diagnóstico por imagen , Articulación Patelofemoral/cirugía , Estudios Retrospectivos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Tibia/cirugía , OsteotomíaRESUMEN
BACKGROUND: We evaluated the relationship between the weight-bearing line (WBL) ratio and anatomical femorotibial angle (FTA) by simulated open wedge high tibial osteotomy (OWHTO). This study evaluated the correlation between the ''Fujisawa point'' and FTA, and identified factors which caused deviations between the two measurement methods. We hypothesized that the Fujisawa point corresponded with 170° of the FTA. METHODS: Preoperative antero-posterior full-length lower limb radiographs of 82 patients were obtained for the OWHTO to place the WBL ratio at a target of 62.5% of the width of the tibial plateau (Fujisawa point). The coronal alignment was measured pre- and post-planning. The patients were divided into two groups by the post-planning FTA: a correspondence group (168.5°â¦FTAâ¦171.5°) and a non-correspondence group (FTA < 168.5°, 171.5° < FTA). The relationship between the Fujisawa point and the FTA was analyzed with multivariate regression analysis. RESULTS: The post-planning FTA was 169.8 ± 1.1° and within 170 ± 1.5° in 69 cases (84.1%) when the WBL ratio was 62.5%. The neck shaft angle was 128.1 ± 5.2° in the correspondence group, and 122.3 ± 6.3° in the non-correspondence group. The multivariate linear regression analysis revealed that the neck shaft angle was the only factor that predicted the correspondence of the Fujisawa point with the FTA at 170° (p = 0.006, odd 1.28). CONCLUSIONS: The post-planning FTA converged at 170° when the WBL ratio passed through the Fujisawa point and the neck shaft angle was the only predictor.
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Articulación de la Rodilla , Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Osteotomía/métodos , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Tibia/cirugía , Soporte de PesoRESUMEN
PURPOSE: To compare the radiographic, clinical, and arthroscopic outcomes of varus osteoarthritic knees treated with an open-wedge high tibial osteotomy (OWHTO) alone or with a double-level osteotomy (DLO). It was hypothesized that treatment with DLO would maintain the joint line obliquity (JLO) and acquire better arthroscopic and clinical outcomes after surgery than OWHTO alone. METHODS: Knees with predicted medial proximal tibial angle (MPTA) > 95° were treated with OWHTO alone or with DLO. Preoperatively, age, body mass index, and hip-knee-ankle angle (HKA) differed between the two groups. Therefore, after adjustment for those factors, 34 knees with OWHTO alone and 34 knees with DLO were compared. On whole-leg radiographs for a single leg, HKA, weightbearing line (WBL) ratio, lateral distal femoral angle (LDFA), MPTA, and JLO were measured before and 2 years after surgery. Clinical outcomes were evaluated by the Knee Society Score (KSS) knee, KSS function, Lysholm, and Knee injury and Osteoarthritis Outcome Score (KOOS) scores before and 2 years after surgery. Arthroscopic findings were obtained before and 1 year after surgery. Various factors were compared between the two groups. RESULTS: JLO increased significantly from 1.4° to 6.3° in the OWHTO group (p < 0.001) and changed from 1.0° to 1.3° in the DLO group (n.s.). Postoperative MPTA and JLO in the OWHTO group were significantly higher than those in the DLO group (both p < 0.001). There were no significant differences in the KSS knee, KSS function, and KOOS scores between the two groups. Postoperative Lysholm score in the DLO group was higher than that in the OWHTO group (p < 0.025). Femoral and tibial cartilage regeneration in the medial condyles and deterioration in the lateral condyles did not differ between the two groups on second-look arthroscopy. CONCLUSIONS: JLO was not significantly changed after surgery in the DLO group. DLO enabled the acquisition of physiological JLO compared with OWHTO alone. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.
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Osteoartritis de la Rodilla , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Osteotomía , Estudios Retrospectivos , Tibia/cirugíaRESUMEN
PURPOSE: The aim of this study was to investigate whether the tibial tuberosity-trochlear groove (TT-TG) distance and lateral patellar tilt, which induce patellofemoral osteoarthritis (OA), are related to the coronal deformity of the lower limb in varus knee OA. It was hypothesized that varus inclination of the tibia was negatively correlated with the TT-TG distance and lateral patellar tilt in Japanese female patients with moderate knee OA. METHODS: A total of 104 female patients (139 knees) scheduled to undergo knee osteotomy for varus knee OA were enrolled. The coronal lower limb alignment was measured on anteroposterior whole-leg radiographs. The TT-TG distance, patellar tilt angle, and the patellofemoral joint space were measured both medially and laterally on computed tomography images. The correlations between coronal lower limb alignment and the TT-TG distance or patellar tilt angle, and the correlations between the TT-TG distance or patellar tilt angle and patellofemoral joint space were evaluated. RESULTS: The medial proximal tibial angle was negatively correlated with the TT-TG distance (r = - 0.383, P < 0.01) and patellar tilt angle (r = - 0.34, P < 0.01). Lateral patellofemoral joint space was negatively correlated with the TT-TG distance (r = - 0.256, P = 0.002) and patellar tilt angle (r = - 0.205, P = 0.016). CONCLUSIONS: Varus inclination of the proximal tibia may induce lateralization of the tibial tuberosity and lateral patellar tilt. The tibial tuberosity lateralization and lateral patellar tilt may induce lateral patellofemoral OA in patients with varus knee OA. LEVEL OF EVIDENCE: III.
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Osteoartritis de la Rodilla/patología , Osteoartritis de la Rodilla/fisiopatología , Articulación Patelofemoral/patología , Articulación Patelofemoral/fisiopatología , Tibia/patología , Tibia/fisiopatología , Adulto , Anciano , Femenino , Humanos , Japón , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Osteotomía , Articulación Patelofemoral/diagnóstico por imagen , Articulación Patelofemoral/cirugía , Radiografía , Tibia/diagnóstico por imagen , Tibia/cirugía , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: This study investigated the relationship between femoral shaft bowing and the orientation of the surgical transepicondylar axis (TEA) in the coronal plane in varus knee osteoarthritis (OA). METHODS: A total of 82 knees scheduled to undergo total knee arthroplasty (TKA) for the treatment of varus knee OA were enrolled. The hip-knee-ankle angle (HKA) was measured preoperatively on anteroposterior whole-leg standing radiographs. The lateral angle between the TEA and the mechanical axis of the femur (MA-TEA) was measured in the coronal plane from preoperative computed tomography (CT) images. Femoral shaft bowing was measured on CT images. Pearson's correlation coefficient was used to examine the correlation of the MA-TEA with the HKA and femoral shaft bowing. RESULTS: The MA-TEA correlated negatively with the HKA (r = - 0.321, P < 0.01) and positively with femoral shaft bowing (r = 0.415, P < 0.01). CONCLUSIONS: The TEA changed to varus as femoral shaft bowing increased in patients with varus knee OA. This suggests that the TEA is not always the centre of the rotational axis of the femur after TKA. In addition, the TEA may not be useful as a consistent parameter in the coronal plane in patients with increasing femoral shaft bowing. LEVEL OF EVIDENCE: III.
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Artroplastia de Reemplazo de Rodilla/métodos , Fémur/cirugía , Genu Varum/cirugía , Osteoartritis de la Rodilla/cirugía , Anciano , Anciano de 80 o más Años , Articulación del Tobillo/diagnóstico por imagen , Femenino , Fémur/diagnóstico por imagen , Humanos , Rodilla/diagnóstico por imagen , Rodilla/cirugía , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Radiografía/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
INTRODUCTION: Preoperative supine joint line convergence angle (JLCA) correlates with postoperative standing JLCA. Here, we compared the radiographic and clinical outcomes of knees with preoperative JLCAs of ≥ 4° and < 4° in open-wedge high tibial osteotomy (OWHTO). We hypothesized that the postoperative coronal alignment in both groups would not be affected by a change in JLCA if this change could predict before surgery. MATERIALS AND METHODS: Eighty-four patients with medial knee osteoarthritis who underwent OWHTO were enrolled retrospectively. A weight-bearing line (WBL) ratio of 62% and a JCLA equivalent to the preoperative supine JLCA were anticipated in preoperative planning. These were intraoperatively set using an alignment rod and a radiolucent protractor under fluoroscopy. Soft tissue correction was defined as correction angle minus bone correction. The participants with preoperative JLCAs of < 4° (low-JLCA group) and ≥ 4° (high-JLCA group) were compared. RESULTS: No significant difference in the coronal alignment was found between the groups after OWHTO. No significant differences in correction angle or bone correction were found between the groups, but the soft tissue correction in the high-JLCA group was higher than that in the low-JLCA group after OWHTO (p = 0.013). CONCLUSIONS: When we controlled intraoperative JLCA, the postoperative coronal alignment was not affected by the change in JLCA and the differences in soft tissue correction between the low-JLCA and high-JLCA groups. However, overcorrection compared with the target coronal alignment remained in both groups. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Articulación de la Rodilla , Osteotomía/métodos , Tibia , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Radiografía , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Tibia/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: To investigate the relationship between femoral or tibial torsion and hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), or mechanical medial proximal tibial angle (mMPTA) in patients with medial knee osteoarthritis (OA). METHODS: A total of 75 knees were enrolled. Femoral and tibial torsions were measured by superimposing the axial planes of computed tomography images. The relationship between femoral or tibial torsion and HKA, mLDFA, or mMPTA on radiographs was examined. RESULTS: The mean femoral torsion was 12.2 ± 8.5° internally; femoral internal and external torsions were observed in 70 and 5 knees, respectively. The mean tibial external torsion was 18.0 ± 7.4° externally; tibial external torsion was observed in all 75 knees. Femoral internal and tibial external torsions increased with lower mMPTA (r = 0.33, P = 0.003; r = - 0.32, P = 0.005, respectively) but were not related to HKA or mLDFA. CONCLUSION: Femoral and tibial torsions were correlated with varus inclination of the proximal tibia in patients with medial knee OA.
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Fémur/diagnóstico por imagen , Extremidad Inferior/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Tibia/diagnóstico por imagen , Torsión Mecánica , Anciano , Fenómenos Biomecánicos , Femenino , Humanos , Japón/epidemiología , Articulación de la Rodilla/diagnóstico por imagen , Persona de Mediana Edad , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
INTRODUCTION: Using a navigation system in open-wedge high tibial osteotomy (OWHTO) has higher accuracy than using the conventional method. However, unintentional over- and under-correction still exist. This study aimed to compare various factors related to over- and under-correction and to assess their predictive factors in the preoperative radiographs. MATERIALS AND METHODS: This study involved 96 knees. The difference in the hip-knee-ankle angle (HKA) between the intraoperative navigation system and postoperative radiograph was termed navigation correction loss (NCL). Knees with absolute values of NCL (|NCL|) ⦠1.5° and |NCL| > 1.5° were categorised into acceptable (n = 46) and outlier (n = 50) groups, respectively. The differences in joint line convergence angle (JLCA) between varus and valgus radiographs, varus JLCA, valgus JLCA, standing JLCA and standing HKA were compared between the two groups. Clinical results were evaluated using the American Knee Society (AKS) scores. RESULTS: The mean intraoperative HKA in the navigation system was - 3.8 ± 1.8°, and that in the postoperative standing radiograph was - 4.2 ± 2.5° (p = 0.033). Preoperative varus, valgus and standing JLCA were higher in the outlier group (p = 0.018, p = 0.020 and p = 0.001, respectively). Logistic regression analyses for preoperative factors of |NCL| ⦠1.5° showed that standing JLCA was a determining factor, with an odds ratio of 1.334 (confidence interval was 1.087-1.637, p = 0.006). AKS score was higher in the acceptable group (p = 0.040) postoperatively. CONCLUSIONS: Higher preoperative standing JLCA was the predictive factor of |NCL| > 1.5°. This factor reduced the rates of under- and over-correction and resulted in better AKS score in OWHTO.
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Extremidad Inferior , Osteotomía , Tibia , Humanos , Extremidad Inferior/diagnóstico por imagen , Extremidad Inferior/cirugía , Osteotomía/métodos , Osteotomía/estadística & datos numéricos , Radiografía , Tibia/diagnóstico por imagen , Tibia/cirugíaRESUMEN
The original version of this article unfortunately contained a mistake. The spelling of the Geert Pagenstert name was incorrect.
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INTRODUCTION: Few studies evaluated clinical benefits of pre-operative templating in total hip arthroplasty (THA). We investigated whether mismatch between planned and real implant sizes and medio-lateral offsets compromises THA outcomes. MATERIALS AND METHODS: We reviewed records of 184 primary THAs with pre-operative CT scans used for templating. Acetabular offset (AO), femoral offset (FO) and global offset (GO) were measured on pre-operative CT scans, during acetate templating, and post-operative antero-posterior radiographs. Multivariable analyses were performed to determine if Forgotten Joint Score (FJS) and Oxford Hip Score (OHS) at > 2 years were associated with differences between post-operative and planned parameters. RESULTS: The FJS and OHS were not influenced by mismatch of component sizes nor of FO and GO. The FJS was better when the post-operative AO was greater than planned (p = 0.050). The FJS differed among arthritic types (p = 0.015). Multivariable analyses confirmed that older patients had better OHS (beta - 0.16; p = 0.033) and FJS (beta 0.74; p = 0.002), medialized hips had worse FJS (beta - 20.1; p = 0.041) and hips with greater AO than planned had better FJS (beta 1.71; p = 0.024) CONCLUSIONS: Implanting a component of different size than planned did not compromise THA outcomes, but medialized hips had worse scores, and conservative acetabular reaming improved scores.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Cuidados Preoperatorios , Acetábulo/diagnóstico por imagen , Acetábulo/cirugía , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Fémur/diagnóstico por imagen , Fémur/cirugía , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/cirugía , Prótesis de Cadera/efectos adversos , Prótesis de Cadera/estadística & datos numéricos , Humanos , Cuidados Preoperatorios/efectos adversos , Cuidados Preoperatorios/métodos , Cuidados Preoperatorios/estadística & datos numéricos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
INTRODUCTION: Pre-operative templating for total hip arthroplasty (THA) remains inaccurate due to improper magnification and alignment. We aimed to describe an improved templating strategy using computed tomography (CT) to predict component sizes and offsets with greater accuracy. MATERIALS AND METHODS: We analysed 184 CT images acquired for pre-operative templating of primary THA. We aimed to restore native (pre-arthritic) femoral offset and limb length, by raising the head center to the level of the templated cup center cranio-caudally, but maintaining the pathologic (pre-operative) head center medio-laterally (except in medialized hips). Acetabular offset (AO) and femoral offset (FO) were measured on pre-operative CT scans, during acetate templating, and on post-operative true antero-posterior radiographs. RESULTS: The post-operative offsets were within ± 5 mm from templated estimates in 174 hips (91%) for AO, in 116 hips (61%) for FO, in 111 hips (58%) for GO, and in 134 hips (70%) for neck cut level. The post-operative hip architecture reproduced the templated hip architecture within ±5 mm in 77 hips (40%). The agreement between planned and post-operative parameters was moderate for stem size (0.57), cup size (0.62), AO (0.50), but fair for FO (0.45). The AO decreased in most arthritic types, notably in lateralized hips (6.6 mm), but remained unchanged in medialized hips. The FO increased in most arthritic types (1.8-3.1 mm) but remained unchanged in medialized and lateralized hips. CONCLUSIONS: We described a strategy for pre-operative templating in THA. Despite the accuracy of CT, the authors found significant variations between planned and post-operative reconstructions, which suggest that pre-operative templating should only be used as an approximate guide.
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Artroplastia de Reemplazo de Cadera/métodos , Articulación de la Cadera , Cuidados Preoperatorios/métodos , Acetábulo/diagnóstico por imagen , Acetábulo/patología , Acetábulo/cirugía , Fémur/diagnóstico por imagen , Fémur/patología , Fémur/cirugía , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/patología , Articulación de la Cadera/cirugía , Humanos , Tomografía Computarizada por Rayos XRESUMEN
Peptide and protein drugs, which are categorized as biologics, exhibit poor membrane permeability. This pharmacokinetic disadvantage has largely restricted the development of noninvasive dosage forms of biologics that deliver into systemic circulation. We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel absorption enhancer to overcome this challenge. Since our previous study revealed that biocompatible poly( N-vinylacetamide- co-acrylic acid) modified with d-octaarginine, a typical cell-penetrating peptide, enhanced in vitro permeation of biomolecules such as plasmid DNA and bovine serum albumin through cell membranes, the present study evaluated whether the polymers enhanced in vivo absorption of biologics applied on the mucosa. Mouse experiments demonstrated that d-octaarginine-linked polymers drastically enhanced nasal absorption of exendin-4, whose injection is clinically used. The mean bioavailability was 20% relative to subcutaneous administration, even though it fell short of 1% when exendin-4 alone was administered nasally. The absorption-enhancing function of the polymers was superior to that of sodium caprate and sodium N-(8-(2-hydroxybenzoyl)amino) caprylate, which have been used for humans as an absorption enhancer. In vitro experiments using several biologics with different characteristics revealed that biologics interacted with d-octaarginine-linked polymers and were taken up into cells when incubated with the polymers. The interaction and cellular uptake were enhanced as molecular weights of the biologics increased; however, their charge-dependent in vitro performance was not clearly observed. The current data suggested that biologics formulated with our polymers became an alternative to their conventional invasive parenteral formulations.
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Exenatida/administración & dosificación , Exenatida/farmacocinética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Oligopéptidos/metabolismo , Vehículos Farmacéuticos/metabolismo , Polímeros/metabolismo , Administración Intranasal , Animales , Línea Celular , Femenino , Ratones , Membrana Mucosa/metabolismo , Oligopéptidos/química , Vehículos Farmacéuticos/química , Polímeros/químicaRESUMEN
BACKGROUND: The carotid bulb has a high density of baroreceptors that play an important role in maintaining blood pressure. We hypothesized that atherosclerosis of the carotid bulb would reflect the severity of orthostatic hypotension more accurately than would atherosclerosis of other carotid artery segments. METHODS: This cross-sectional study included 198 non-diabetic adults. We measured the cardio-vascular ankle index as an index of arterial stiffness, intima-media thickness in each carotid artery segment (internal carotid artery, carotid bulb, distal and proximal portions, respectively, of the common carotid artery) as a measure of atherosclerosis, and heart rate variability as a measure of cardiac autonomic function. The sit-to-stand test was used to assess severity of orthostatic hypotension. RESULTS: Intima-media thickness of the carotid bulb was correlated with orthostatic systolic blood pressure change (r = -0.218, p = 0.002), cardio-ankle vascular index (r = 0.365, p < 0.001) and heart rate variability parameters. Multivariate regression analysis revealed that among all of the segments, only intima-media thickness of the carotid bulb was an independent predictor of orthostatic systolic blood pressure change (p = 0.022). CONCLUSION: Atherosclerosis of the carotid bulb was associated with severity of orthostatic hypotension, arterial stiffening and cardiac autonomic dysfunction than that of other carotid artery segments.
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PURPOSE: To evaluate the effects of osteochondral autograft transplantation (OAT) mosaicplasty as a concomitant procedure with opening-wedge valgus high tibial osteotomy (HTO) for spontaneous osteonecrosis of the medial femoral condyle (MFC) on clinical outcomes and cartilage status in comparison with bone marrow stimulation (BMS) by drilling, and to assess the relation between lesion size and postoperative cartilage status. METHODS: Fifty-eight patients with spontaneous osteonecrosis of the MFC were treated with opening-wedge HTO and a concomitant procedure of BMS (28 patients) or OAT (30 patients). Clinical evaluation was carried out using the Knee Society Score at postoperative 2 years. Postoperative status of articular cartilage was assessed by arthroscopy according to the International Cartilage Repair Society (ICRS) grade at the time of plate removal. RESULTS: The Knee Society Score objective score and function score were improved at postoperative 2 years compared with preoperative value in both groups, but no significant difference was found between the 2 groups. According to the ICRS overall repair grade, cartilage status was rated as normal or nearly normal (ICRS overall score ≥8) in 41% of the BMS group and 90% of the OAT group. The results suggested that cartilage repair in OAT was significantly better than that in BMS (P = .0015). Furthermore, the BMS group revealed that repair with normal or nearly normal was observed in all less than 4 cm2 of lesion size, whereas the OAT group exhibited that repair with normal or nearly normal was independent of lesion size. CONCLUSIONS: This study suggested that OAT is superior to BMS as a concomitant procedure with opening-wedge valgus HTO for spontaneous osteonecrosis of the MFC in the success of cartilage repair. However, clinical outcomes were not significantly different between these 2 procedures. When treating the lesion larger than 4 cm2 by joint-preserving surgery, OAT mosaicplasty is recommended as a concomitant procedure with HTO. LEVEL OF EVIDENCE: Level III, therapeutic case-control study.
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Médula Ósea/cirugía , Cartílago Articular/cirugía , Fémur/cirugía , Articulación de la Rodilla/cirugía , Osteonecrosis/cirugía , Osteotomía/métodos , Anciano , Anciano de 80 o más Años , Artroscopía/métodos , Autoinjertos , Estudios de Casos y Controles , Terapia Combinada , Femenino , Fémur/patología , Humanos , Articulación de la Rodilla/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tibia/cirugía , Trasplante Autólogo , Resultado del TratamientoRESUMEN
PURPOSE: To assess whether the increased inclination of the tibial plateau on the coronal view after opening-wedge high tibial osteotomy affects radiographic coronal alignment, clinical outcomes, and cartilage findings. METHODS: After adjustment for the preoperative medial proximal tibial angle (MPTA), patients who underwent opening-wedge high tibial osteotomy were retrospectively divided into those with postoperative MPTA values of 95° or less (normal group) and greater than 95° (increased group), with each group containing 43 knees. The 2 groups were compared regarding their arthroscopic cartilage findings at 1 year postoperatively and radiographic coronal alignment and clinical outcomes at 2 years postoperatively. Cartilage regeneration in the medial condyles and cartilage deterioration in the lateral condyles were evaluated at the time of second-look arthroscopy. Clinical outcomes were evaluated by the American Knee Society knee and function scores, Lysholm knee scoring scale, and Knee Injury and Osteoarthritis Outcome Score (KOOS). RESULTS: The postoperative anatomic femorotibial angle in the increased group was lower than that in the normal group (P < .001), and the amount of overcorrection in the increased group was higher than that in the normal group (P < .001). The postoperative joint line obliquity in the increased group was higher than that in the normal group (P < .001). Cartilage regeneration in the medial condyles and deterioration in the lateral condyles did not differ significantly on the femoral and tibial sides between the groups. The postoperative American Knee Society knee score and KOOS sports and recreational function subscale score in the normal group were higher than those in the increased group (both P < .001). CONCLUSIONS: There were no significant differences in the changes in the appearance of the articular surfaces between the 2 groups at 1 year postoperatively. Patients with a postoperative MPTA greater than 95° had more valgus alignment and higher joint line obliquity and had a lower KOOS sports and recreational function subscale score than patients with a postoperative MPTA of 95° or less at 2 years postoperatively. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
Asunto(s)
Traumatismos de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Osteotomía , Tibia/cirugía , Anciano , Artroscopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Rango del Movimiento Articular , Estudios Retrospectivos , Segunda Cirugía , Tibia/diagnóstico por imagen , Resultado del TratamientoRESUMEN
INTRODUCTION: Rotational malpositioning of the tibial component can lead to poor functional outcome in TKA. Although various surgical techniques have been proposed, precise rotational placement of the tibial component was difficult to accomplish even with the use of a navigation system. The purpose of this study is to assess whether combined CT-based and image-free navigation systems replicate accurately the rotational alignment of tibial component that was preoperatively planned on CT, compared with the conventional method. MATERIALS AND METHODS: We compared the number of outliers for rotational alignment of the tibial component using combined CT-based and image-free navigation systems (navigated group) with those of conventional method (conventional group). Seventy-two TKAs were performed between May 2012 and December 2014. In the navigated group, the anteroposterior axis was prepared using CT-based navigation system and the tibial component was positioned under control of the navigation. In the conventional group, the tibial component was placed with reference to the Akagi line that was determined visually. Fisher's exact probability test was performed to evaluate the results. RESULTS: There was a significant difference between the two groups with regard to the number of outliers: 3 outliers in the navigated group compared with 12 outliers in the conventional group (P < 0.01). CONCLUSIONS: We concluded that combined CT-based and image-free navigation systems decreased the number of rotational outliers of tibial component, and was helpful for the replication of the accurate rotational alignment of the tibial component that was preoperatively planned.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/métodos , Cirugía Asistida por Computador , Tibia , Tomografía Computarizada por Rayos X , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/estadística & datos numéricos , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/cirugía , Periodo Posoperatorio , Tibia/diagnóstico por imagen , Tibia/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: This study documented the healing potential of degenerated articular cartilage after opening-wedge valgus high tibial osteotomy (HTO) in patients with osteoarthritis of the knee. It was hypothesized that regeneration of articular cartilage is affected by several factors, including preoperative cartilage degeneration grade, difference between the medial femoral condyle (MFC) and the medial tibial condyle (MTC), and postoperative knee alignment. METHODS: Medial opening-wedge valgus HTO was performed in 131 knees of 100 patients (mean age 66 ± 7.7 years). Initial arthroscopy was performed at the time of HTO, and a second-look arthroscopy was performed at the time of plate removal (20.8 ± 6.5 months after HTO). Status of articular cartilage was assessed according to the ICRS grade. Cartilage regeneration was also evaluated by the presence of newly formed cartilaginous tissue. All subjects were followed up postoperatively at 2 years for assessment of clinical and radiographic outcomes. RESULTS: The number of subjects in ICRS grade 1/2/3/4 was significantly altered from 0/11/53/67 preoperatively to 14/21/56/40 postoperatively in the MFC (P < 0.05) and 0/12/62/57 preoperatively to 9/24/64/34 postoperatively in the MTC (P < 0.05). Newly formed cartilaginous tissue was found in 71 % of MFCs and 51 % of MTCs. Incidence of cartilage regeneration was significantly higher in lower BMI cases, MFC, preoperatively advanced ICRS grade and overcorrected knees. Age, gender and clinical outcomes did not affect cartilage regeneration. CONCLUSION: Cartilage regeneration in degenerated articular cartilage is induced after opening-wedge valgus HTO, which is affected by BMI, the difference between the MFC and MTC, preoperative cartilage degeneration grade, and postoperative limb alignment. Therefore, patient selection by BMI rather than age, and surgical techniques maintaining valgus knee alignment should be considered for cartilage regeneration. LEVEL OF EVIDENCE: Level IV, therapeutic case series.
Asunto(s)
Cartílago Articular/cirugía , Articulación de la Rodilla/cirugía , Osteotomía/métodos , Tibia/cirugía , Anciano , Artroscopía , Femenino , Fémur/cirugía , Humanos , Masculino , Osteoartritis de la Rodilla/cirugía , Regeneración , Segunda Cirugía , Cicatrización de HeridasRESUMEN
PURPOSE: This study aimed to investigate the incidence of venous thromboembolism (VTE) after medial opening-wedge high tibial osteotomy (OWHTO) and evaluate the efficacy and safety of edoxaban for the prevention of VTE in patients undergoing OWHTO. METHODS: A total of 139 patients with osteoarthritis or osteonecrosis undergoing OWHTO were enrolled in this prospective, randomized study. Four patients were excluded because of preoperatively diagnosed VTE, and 135 patients were divided into two groups-an edoxaban group and a non-edoxaban group-and underwent computed tomography venography on day 7 to check for postoperative VTE. Blood samples were taken on the day before OWHTO and on postoperative days 1, 3, 7, and 14. RESULTS: Treatment with edoxaban reduced the incidence of VTE after OWHTO; however, there was no statistically significant difference between the two groups. No major bleeding was noted in the edoxaban group. There were significant differences in the D-dimer level, prothrombin time, fibrinogen level, and thrombin antithrombin complex levels between the groups. CONCLUSIONS: Edoxaban is an oral, once-daily, selective, direct factor Xa inhibitor that is safe and easy to handle. It may offer a new option for preventing VTE after OWHTO. LEVEL OF EVIDENCE: I.