Standardized approach for accurate and reliable model development of ion-exchange chromatography based on parameter-by-parameter method and consideration of extra-column effects.

Developing an accurate and reliable model for chromatographic separation that meets regulatory requirements and ensures consistency in model development remains challenging. In order to address this challenge, a standardized approach was proposed in this study with ion-exchange chromatography (IEC). The approach includes the following steps: liquid flow identification, system and column-specific parameters determination and validation, multi-component system identification, protein amount validation, steric mass action parameters determination and evaluation, and validation of the calibrated model's generalization ability. The parameter-by-parameter (PbP) calibration method and the consideration of extra-column effects were integrated to enhance the accuracy of the developed models. The experiments designed for implementing the PbP method (five gradient experiments for model calibration and one stepwise experiment for model validation) not only streamline the experimental workload but also ensure the extrapolation abilities of the model. The effectiveness of the standardized approach is successfully validated through an application about the IEC separation of industrial antibody variants, and satisfactory results were observed with R2 ≈ 0.9 for the majority of calibration and validation experiments. The standardized approach proposed in this work contributes significantly to improve the accuracy and reliability of the developed IEC models. Models developed using this standardized approach are ready to be applied to a broader range of industrial separation systems, and are likely find further applications in model-assisted decision-making of process development.

Modified hindfoot alignment radiological evaluation and application in the assessment of flatfoot.

BACKGROUND: Alignment is indispensable for the foot and ankle function, especially in the hindfoot alignment. In the preoperative planning of patients with varus or valgus deformity, the precise measurement of the hindfoot alignment is important. A new method of photographing and measuring hindfoot alignment based on X-ray was proposed in this study, and it was applied in the assessment of flatfoot. METHODS: This study included 28 patients (40 feet) with flatfeet and 20 volunteers (40 feet) from January to December 2018. The hindfoot alignment shooting stand independently designed by our department was used to take hindfoot alignment X-rays at 10 degree, 15 degree, 20 degree, 25 degree, and 30 degree. We measured the modified tibio-hindfoot angle (THA) at the standard hindfoot aligment position (shooting at 20 degree) and evaluated consistency with the van Dijk method and the modified van Dijk method. In addition, we observed the visibility of the tibiotalar joint space from all imaging data at five projection angles and evaluated the consistency of the modified THA method at different projection angles. The angle of hindfoot valgus of flatfoot patients was measured using the modified THA method. RESULTS: The mean THA in the standard hindfoot aligment view in normal people was significantly different among the three evaluation methods (P < .001). The results from the modified THA method were significantly larger than those from the Van Dijk method (P < .001) and modified Van Dijk method (P < .001). There was no significant difference between the results of the modified THA method and the weightbearing CT (P = .605), and the intra- and intergroup consistency were the highest in the modified THA group. The tibiotalar space in the normal group was visible in all cases at 10 degree, 15 degree, and 20 degree; visible in some cases at 25 degree; and not visible in all cases at 30 degree. In the flatfoot group, the tibiotalar space was visible in all cases at 10 degree, visible in some cases at 15 degree and 20 degree, and not visible in all cases at 25 degree and 30 degree. In the normal group, the modified THA was 4.84 ± 1.81 degree at 10 degree, 4.96 ± 1.77 degree at 15 degree, and 4.94 ± 2.04 degree at 20 degree. No significant differences were found among the three groups (P = .616). In the flatfoot group, the modified THA of 18 feet, which was visible at 10 degree, 15 degree and 20 degree, was 13.58 ± 3.57 degree at 10 degree, 13.62 ± 3.83 degree at 15 degree and 13.38 ± 4.06 degree at 20 degree. There were no significant differences among the three groups (P = .425). CONCLUSIONS: The modified THA evaluation method is simple to use and has high inter- and intragroup consistency. It can be used to evaluate hindfoot alignment. For patients with flatfeet, the 10 degree position view and modified THA measurement can be used to evaluate hindfoot valgus.

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy.

Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF-α, IL-1ß, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1ß, IL-6, and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

[Comparison of efficacy of platelet-rich plasma and extracorporeal shock wave for the treatment of chronic insertional Achilles tendinopathy].

OBJECTIVE: To compare clinical efficacy of platelet-rich plasma (PRP) and extracorporeal shock wave in treating chronic insertional Achilles tendinopathy. METHODS: From February 2019 to August 2021, 42 patients with chronic insertional Achilles tendinopathy were selected and divided into PRP group(20 patients, 28 feet) and shock wave group (22 patients, 29 feet). In PRP group, there were 12 males and 8 females, aged 47.00(28.00, 50.75) years old, and the courses of disease ranged 7.00(6.00, 7.00) months;PRP injection was performed in the Achilles tendon stop area of the affected side. In shock wave group, there were 16 males and 6 females, aged 42.00(35.75, 47.25) years old;and the courses of disease was 7.00(6.00, 8.00) months;shock wave was performed in Achilles tendon stop area of the affected side and triceps surae area. Visual analogue scale (VAS) and Victorian Institute of Sport Assessment-Achilles (VISA-A) were applied to evaluate clnical effect before treatment, 1, 3 and 6 months after treatment, and satisfaction of patients was investigated. RESULTS: VAS and VISA-A score in both groups were significantly improved at 1, 3 and 6 months after treatment than before treatment (P<0.05), VAS and VISA-A score in PRP group at 6 months after treatment were significantly higher than those at 1 and 3 months after treatment, and VAS and VISA-A score in shock wave group were lower than those at 1 and 3 months after treatment (P<0.05). There was no significant difference in VAS and VISA-A score between two groups before treatment, 1 and 3 months after treatment(P>0.05), while VAS and VISA-A score in PRP group were better than those in shock wave group at 6 months after treatment(P<0.05), and the satisfaction survey in PRP group was better than that in shock wave group(P<0.05). CONCLUSION: PRP injection has a good clinical effect on chronic insertional Achilles tendinopathy with high patient satisfaction, and medium-and long-term effect of PRP injection for the treatment of chronic insertional Achilles tendinopathy is better than that of extracorporeal divergent shock wave.

Supramalleolar Osteotomy vs Arthrodesis for the Treatment of Takakura 3B Ankle Osteoarthritis.

BACKGROUND: To compare the clinical/functional outcomes of supramalleolar osteotomy (SMOT) and ankle arthrodesis (AA) for the treatment of modified Takakura stage 3B ankle osteoarthritis. METHODS: Outcomes of 28 SMOT patients and 30 AA patients were reviewed at an average of 50 and 51 months, respectively. The baseline characteristics of the 2 groups were similar. The preoperative tibial articular surface angle and talar tilt angle in the SMOT group were 82.6 and 10 degrees and in the AA group, 83.9 and 9.1 degrees, respectively. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, visual analog scale (VAS) score, 12-item Short-Form Health Survey (SF-12) mental component summary (MCS) and physical component summary (PCS) scores, range of motion (ROM), radiologic parameters, and complications were compared. RESULTS: The AOFAS, VAS, and SF-12 MCS and PCS scores improved significantly postoperatively in both groups (P < .001). The VAS and SF-12 PCS scores indicate marginally better improvement in the AA group (P < .05). The patient satisfaction value (P = .028) and the possibility of repeated surgery value (P = .012) were also significantly higher in the AA group. The early (P = .905) and late (P = .181) complications did not significantly differ between the 2 groups. The reoperation rate was significantly higher in the SMOT group (P = .038). CONCLUSION: Both SMOT and AA showed improvements in function, pain, alignment, and quality of life after surgery. Patients in the AA group reported better pain relief, had a lower reoperation rate, and better hindfoot alignment during a short- to mid-term follow-up time. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Closed reduction and posterior percutaneous internal fixation for simple displaced talar neck fracture: a retrospective comparative study.

PURPOSE: Open reduction and internal fixation (ORIF) is the most commonly used surgical technique for talar neck fracture, but there are high risks for complications and poor functional outcomes. In this study, we reported the closed reduction and percutaneous internal fixation (CRPIF) technique of the bilateral approach of the Achilles tendon for simple displaced talar neck fracture, in comparison with ORIF. METHODS: Data of 15 patients in the CRPIF group and 22 in the ORIF group were included. The American Orthopaedic Foot and Ankle Society (AOFAS) score, Visual Analog Scale (VAS) score, 12-item Short-Form Survey (SF-12) score, range of motion (ROM), complications, and radiographic results were recorded and compared. RESULTS: The mean follow-up in the CRPIF group was 33.9 months. Complications included two cases of avascular necrosis (AVN) and two cases of osteoarthritis. All patients achieved bony union and recovered their pre-operative mobility. The mean follow-up in the ORIF group was 39 months. Complications included two cases of bony nonunion, nine AVN, and seven cases of osteoarthritis. Moreover, the mobility of the ORIF group was significantly lower than the CRPIF group post-operatively. The AOFAS score, VAS score, and SF-12 physical component score (PCS) for the CRPIF group were better improved than those for the ORIF group (ALL, P < 0.05). CONCLUSIONS: The CRPIF technique of the bilateral approach of the Achilles tendon was an effective method for the treatment of simple displaced talar neck fractures. Compared with the ORIF, the limited blood supply of the talus was protected, provide better functional outcomes and biomechanical fixation, and lower incidence of resurgery and complication in the CRPIF.

Triplane osteotomy combined with talar non-weight-bearing area autologous osteochondral transplantation for osteochondral lesions of the talus.

BACKGROUND: Traditional medial malleolar osteotomy combined with autologous osteochondral transplantation (AOT) is mostly used in the treatment of osteochondral lesions of the talus (OLTs), but with high osteotomy and donor site complications. We hypothesis a new triplane medial malleolar osteotomy combined with AOT from non-weight-bearing area of the talus could be a promising choice for OLTs. METHODS: We reviewed all the symptomatic OLTs patients who received AOT with triplane osteotomy of the medial malleolus between September 2015 and December 2017 in our department. According to the inclusion and exclusion criteria, 23 patients (23 ankles), including 14 males and 9 females, were included in the study. The mean age was 35.6 years. The mean size of the lesion area was 141.5 mm2. According Ferkel's classification, including 5 type I, 11 typeIIa and 7 typeIIb. The visual analog scale (VAS) for pain during walking and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used for the pre- and postoperative evaluations. In addition, the incorporation of the grafts was assessed by computed tomography (CT). RESULTS: All patients had a minimum follow-up of 22 months, with an average of 37.1 months. The mean time from osteotomy to full weight-bearing activity was 8.1 ± 2.3 weeks (range, 5-12 weeks). The mean VAS score improved from 5.6 ± 0.7 preoperatively to 0.7 ± 1.0 postoperatively (P < 0.01). The AOFAS ankle-hindfoot score improved significantly in all domains (P < 0.01). Twenty-one patients returned to sport at their previous level, and 2 returned at a lower level compared with preinjury (mean return to play, 7.4 months). According to CT, the medial malleolus recovered in all patients, and the graft was incorporated well. One patient suffered from flexor hallucis longus tendon discomfort due to internal fixation screw irritation posteromedial to the ankle. The general complication rate was 4.3% (1/23). CONCLUSIONS: These results indicate that AOT combined with medial malleolus triplane osteotomy maybe a viable option for OLTs. Patients could perform weight-bearing exercise and return to sport as early as possible, with a lower rate of complications at the osteotomy site and donor site. However, the large sample well-designed prospective comparative studies are still needed.

Fibular osteotomy is helpful for talar reduction in the treatment of varus ankle osteoarthritis with supramalleolar osteotomy.

BACKGROUND: There have been debates on the necessity of fibular osteotomy (FO) in supramalleolar osteotomy (SMOT) for the treatment of varus ankle osteoarthritis. The purpose of the current study was to compare the clinical and radiological outcomes between SMOT with and without FO in the treatment of varus ankle osteoarthritis. METHODS: The SMOT group included 39 patients, and the SMOT with FO group included 24 patients. The basic information reached no significant difference between groups. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Ankle Osteoarthritis Scale (AOS), modified Takakura stage and range of motion (ROM) were used for the functional evaluation. The radiologic parameters were assessed at the last follow-up to compare the degree of talar reduction between the two groups. RESULTS: Both groups achieved significant improvements in AOFAS scores, modified Takakura stage, as well as AOS pain and functional scores (P < 0.001). The ROM of the ankle joint in the SMOT group was significantly decreased (P = 0.022). In both groups, all of the radiological parameters were significantly improved (P < 0.01). The tibiofibular clear space (TFCS) was significantly widened in the SMOT group (P < 0.001). No significant difference was found between the two groups according to the functional outcomes. However, the talar tilt angle (TT) and hindfoot alignment angle (HFA) in the SMOT with FO group were significantly smaller than those in the SMOT group (P < 0.05). The TFCS was significantly widened in the SMOT group (P = 0.001). The medial displacement of the talus (MDT) was better reduced in the SMOT with FO group (P = 0.006). CONCLUSION: SMOT is a promising procedure for functional improvement and malalignment correction in varus ankle osteoarthritis but reduces ankle range of motion. If SMOT is combined with FO, talar tilt and medial displacement will be better reduced.

Ilizarov Gradual Distraction Correction for Distal Tibial Severe Varus Deformity Resulting from Epiphyseal Fracture: Case Report and Literature Review.

We present a case of a 13-year-old female with severe varus deformity and limb discrepancy resulting from epiphyseal fracture. The preoperative tibial articular surface angle was 64.1°, and the affected tibia was 14 mm shorter than the contralateral tibia. She underwent a medial open osteotomy and fibular osteotomy with gradual distraction correction using Ilizarov fixator. The deformity was corrected at 3 months, and the external fixator was removed when bony union was achieved 6 months postoperatively. At 9 months after surgery, the patient could play basketball without feeling pain. At the last follow-up, namely 36 months after the operation, the American Orthopaedic Foot and Ankle Society hindfoot-ankle score was improved from 58 to 90, the patient was pain free, and the radiological measurements were nearly normal. Ilizarov fixator gradual distraction correction for distal tibial severe varus deformity is a safe and cost-effective method that can yield excellent radiological and clinical outcomes.

Supramalleolar osteotomy with medial distraction arthroplasty for ankle osteoarthritis with talar tilt.

BACKGROUND: An increased preoperative talar tilt (TT) angle was reported to be positively correlated with treatment failure after supramalleolar osteotomy (SMOT) for varus ankle osteoarthritis. Distraction arthroplasty was reported to have the ability to correct increased TT angles. The purpose of the current study was to compare the outcomes between SMOT with and without medial distraction arthroplasty (MDA) in the treatment of varus ankle osteoarthritis with increased TT angles. METHODS: We retrospectively reviewed the functional outcomes and radiological findings of 34 patients who underwent SMOT with or without MDA for varus ankle osteoarthritis with increased TT angles. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and Ankle Osteoarthritis Scale (AOS) scores were used for functional evaluation. The tibial anterior surface (TAS) angle, talar tilt (TT) angle, tibial medial malleolar (TMM) angle, talocrural (TC) angle, tibial lateral surface (TLS) angle, and hindfoot alignment (HFA) angle were evaluated preoperatively and at the time of the last follow-up. RESULTS: In the SMOT group, the AOFAS score and AOS pain and function scores were significantly improved (P < 0.01 for each) at a mean follow-up of 61 months. The TAS, TT, TC, TLS, and HFA angles were all significantly improved (P < 0.01 for each). Similarly, in the SMOT with MDA group, the AOFAS score, AOS pain and function scores, and the TAS, TT, TC, TLS, and HFA angles were all significantly improved postoperatively (P < 0.01 for each). When comparing the two groups, the postoperative TT angle was significantly smaller in the SMOT with MDA group (P = 0.023) than in the SMOT group. In addition, the failure rate of TT angle correction was significantly higher in the SMOT group (P = 0.016) than in the SMOT with MDA group. CONCLUSION: SMOT is a promising procedure for functional improvement and malalignment correction for varus ankle osteoarthritis, even in patients with increased talar tilt. If SMOT is combined with MDA, there can be an improvement in the correction of the increased talar tilt. LEVEL OF EVIDENCE: Level III, a retrospective comparative study.