Quantitative assessment of anterior talofibular ligament quality in chronic lateral ankle instability using magnetic resonance imaging T2* value.

OBJECTIVE: To determine T2* normal reference values for anterior talofibular ligament (ATFL) and to investigate the feasibility of the quantitative ATFL quality evaluation in chronic lateral ankle instability (CLAI) using T2* values. MATERIALS AND METHODS: This study enrolled 15 patients with CLAI and 30 healthy volunteers. The entire ATFL T2* values from the MRI T2* mapping were measured. The prediction equation (variables: age, height, and weight) in a multiple linear regression model was used to calculate the T2* normal reference value in the healthy group. T2* ratio was defined as the ratio of the actual T2* value of the patient's ATFL to the normal reference value for each patient. A Telos device was used to measure the talar tilt angle (TTA) from the stress radiograph. RESULTS: T2* values of ATFL in the healthy and CLAI groups were 10.82 ± 1.84 ms and 14.36 ± 4.30 ms, respectively, which are significantly higher in the CLAI group (P < 0.05). The prediction equation of the normal reference T2* value was [14.9 + 0.14 × age (years) - 4.7 × height (m) - 0.03 × weight (kg)] (R2 = 0.65, P < 0.0001). A significant positive correlation was found between the T2* ratio and TTA (r = 0.66, P = 0.007). CONCLUSION: MRI T2* values in patients with CLAI were higher than those in healthy participants, and the T2* ratio correlated with TTA, suggesting that T2* values are promising for quantitative assessment of ATFL quality preoperatively.

Isolation and Structure Determination of New Pyrones from Dictyostelium spp. Cellular Slime Molds Coincubated with Pseudomonas spp.

Cellular slime molds are excellent model organisms in the field of cell and developmental biology because of their simple developmental patterns. During our studies on the identification of bioactive molecules from secondary metabolites of cellular slime molds toward the development of novel pharmaceuticals, we revealed the structural diversity of secondary metabolites. Cellular slime molds grow by feeding on bacteria, such as Klebsiella aerogenes and Escherichia coli, without using medium components. Although changing the feeding bacteria is expected to affect dramatically the secondary metabolite production, the effect of the feeding bacteria on the production of secondary metabolites is not known. Herein, we report the isolation and structure elucidation of clavapyrone (1) from Dictyostelium clavatum, intermedipyrone (2) from D. magnum, and magnumiol (3) from D. intermedium. These compounds are not obtained from usual cultural conditions with Klebsiella aerogenes but obtained from coincubated conditions with Pseudomonas spp. The results demonstrate the diversity of the secondary metabolites of cellular slime molds and suggest that widening the range of feeding bacteria for cellular slime molds would increase their application potential in drug discovery.

Characteristics of Nonunion After Arthroscopic Ankle Arthrodesis: A Multicenter Retrospective Cohort Study.

Nonunion is a major complication of arthroscopic ankle arthrodesis. However, the characteristics and risk factors of nonunion are not well understood. This retrospective multicenter observational study aimed to clarify the characteristics of nonunion after arthroscopic ankle arthrodesis. We included 154 patients who underwent arthroscopic ankle arthrodesis at any 1 of 5 institutions. Patients were divided into 2 groups: union and nonunion, and the groups were compared. Age, sex, body mass index, diabetes, smoking, corticosteroid use, diagnosis, treatment information, treatment protocol, radiographic evaluation, and patient-reported outcomes were recorded and analyzed. On radiographs, bony union was observed in 142 ankles (91.0%) but not in 12 ankles (9.0%). Postoperative radiographic tibial bony gap (mm) was significantly larger in the nonunion group (medial = 1.98, center = 1.65, anterior = 2.21, middle = 1.72, posterior = 3.01) than in the union group (medial = 1.35, center = 1.13, anterior = 1.28, middle = 1.03, posterior = 2.03). Furthermore, the visual analog score (VAS) of pain and pain-related self-administered foot evaluation questionnaire (SAFE-Q) subscale score significantly worsened in the nonunion group (VAS = 3.83, SAFE-Q subscale score = 69.8) compared to that in the union group (VAS = 1.35, SAFE-Q subscale score = 76.6). A larger radiographic tibiotalar bony gap was observed in the nonunion group. Other measurement outcomes were not associated with nonunion. Additionally, patient-reported outcomes markedly worsened in the nonunion group.

High reproducibility of a novel supported anterior drawer test for diagnosing ankle instability.

BACKGROUND: The manual traditional anterior drawer test (ADT) is essential for deciding the treatment for chronic ankle instability, but it has been shown to have a comparatively low reproducibility and accuracy, especially in less experienced hands. To clarify the inter-examiner reproducibility, we compared the actual distance of anterior translation between junior and senior examiners in ADT. We also evaluated the diagnostic abilities of traditional ADT, and a novel modified ADT (supported ADT). METHODS: Thirty ankles were included in this study, and ankle instability was defined using stress radiography. All subjects underwent two methods of manual ADT by junior and senior examiners, and ankle instability was judged in a blinded fashion. The anterior drawer distance was calculated from the lengthening measured using a capacitance-type sensor device. RESULTS: The degree of anterior translation determined by the junior examiner was significantly lower than that determined by the senior examiner when traditional ADT was performed (3.3 vs. 4.5 mm, P = 0.016), but there was no significant difference in anterior translation between the two examiners when supported ADT was performed (4.6 vs. 4.1 mm, P = 0.168). The inter-examiner reliability of supported ADT was higher than that of traditional ADT. For the junior examiner, the diagnostic accuracy of supported ADT was higher than that of traditional ADT (sensitivity, 0.40 vs. 0.80; specificity, 0.75 vs. 0.80). CONCLUSION: Supported ADT may have the advantage of being a simple manual test of ankle instability with less error between examiners.

Surgically treated reactive arthritis of the ankle after COVID-19 infection: A case report.

A 37-year-old man developed right ankle pain and swelling six days after being diagnosed with coronavirus disease (COVID-19). Despite conservative treatment, his ankle symptoms persisted. Magnetic resonance imaging and computed tomography showed synovial hypertrophy and bone erosion in the ankle. Following arthroscopic synovectomy, performed 69 days after the COVID-19 diagnosis, the pain improved significantly. The clinical course was consistent with that of reactive arthritis following severe acute respiratory syndrome coronavirus 2 infection. The pathological findings resembled rheumatoid nodules. The bone erosion may have originated from the inflammatory pathway, which resembles the mechanism of rheumatoid arthritis.

Effect of early mobilization in patients with stroke and severe disturbance of consciousness: Retrospective study.

OBJECTIVES: This study aimed to investigate the effectiveness and safety of early mobilization with a physiatrist and registered therapist Operating rehabilitation (PROr) for patients with stroke and severe disturbance of consciousness (DoC). MATERIALS AND METHODS: We retrospectively screened records from patients with stroke admitted to our hospital from January 2015 to June 2021. Eligible patients with severe DoC were classified into two groups: patients who received standard rehabilitation (control group) and patients who received PROr (PROr group). We studied longitudinal change in the level of consciousness using the Japan Coma Scale (JCS) during hospital stay and compared in-hospital mortality, the incidence of respiratory complication, and modified Rankin Scale of discharge between the two groups. RESULTS: Among the 2191 patients screened for inclusion, 16 patients were included in the PROr group, and 12 patients were included in the control group. Early mobilization was more promoted in the PROr group compared to the control group, but there were no significant differences in in-hospital mortality, the incidence of respiratory complication, or modified Rankin Scale at discharge between the two groups. In patients who survived during their hospital stay, JCS scores 2 weeks after the onset of stroke and JCS scores at discharge significantly improved from the start of rehabilitation in the PROr group, but not in the control group. CONCLUSIONS: Early mobilization provided with the PROr program appears to be a safe treatment and may contribute to the improvement of consciousness level for patients with acute stroke and severe DoC.

Relationship Between Plantar Callosity and Foot Deformity in Hallux Valgus Using Weightbearing Computed Tomography.

Plantar callosities under lesser metatarsals are often accompanied by the hallux valgus, and the cause of callosity is thought to be associated with the foot deformity, such as the metatarsal length discrepancy, the abnormal metatarsal head height, cavus, flat foot, and rheumatoid conditions. However, it is unclear which variable is most involved in the cause of callosity in hallux valgus deformity. To clarify the factors associated with the callosity with hallux valgus deformity, we conducted multiple image assessments based on weightbearing radiography and computed tomography. A retrospective review was performed based on the collection of clinical records from all patients with hallux valgus treated from 2010 to 2019 in our institution. We measured the hallux valgus angle, intermetatarsal angles, calcaneal pitch angles, talo-first metatarsal angles, metatarsal length, metatarsal head height, first metatarsal pronation angles, and sesamoid position with weightbearing radiography and computed tomography. We analyzed the relation between callosity formation and imaging assessments using univariate and multivariate logistic regression models. Fifty feet were retrospectively evaluated, and multiple logistic analyses by the stepwise method revealed that the first metatarsal-lateral-sesamoid distance was the only radiographical variable associated with callosity formation among all the tested variables (p < .001). As the grade of the callosity became more severe, the lateral shift of the lateral sesamoid increased. The position of the sesamoid bone appears to have a critical role in the assessment and choice of treatment protocols and further research needs to be conducted on the relationship with the position of sesamoid bone to elucidate the mechanism of callus formation.

Two New Terpenes Isolated from Dictyostelium Cellular Slime Molds.

We report a protoilludane-type sesquiterpene, mucoroidiol, and a geranylated bicyclogermacranol, firmibasiol, isolated from Dictyostelium cellular slime molds. The methanol extracts of the fruiting bodies of cellular slime molds were separated by chromatographic methods to give these compounds. Their structures have been established by several spectral means. Mucoroidiol and firmibasiol are the first examples of more modified and oxidized terpenoids isolated from cellular slime molds. Mucoroidiol showed moderate osteoclast-differentiation inhibitory activity despite demonstrating very weak cell-proliferation inhibitory activity. Therefore, cellular slime molds produce considerably diverse secondary metabolites, and they are promising sources of new natural product chemistry.

A pleckstrin homology-like domain is critical for F-actin binding and cofilin-phosphatase activity of Slingshot-1.

Slingshot-1 (SSH1) is a protein phosphatase that specifically dephosphorylates and activates cofilin, an F-actin-severing protein. SSH1 binds to and co-localizes with F-actin, and the cofilin-phosphatase activity of SSH1 is markedly increased by binding to F-actin. In this study, we performed a secondary structure analysis of SSH1, which predicted the existence of a pleckstrin homology (PH)-like domain in the N-terminal region of SSH1. SSH1 also contains a DEK-C domain in the N-terminal region. The N-terminal fragment of SSH1 bound to and co-localized with F-actin, but mutation at Arg-96 or a Leu-His-Lys (LHK) motif in the PH-like domain reduced this activity. Furthermore, mutation at Arg-96 abrogated the cofilin-phosphatase activity of SSH1 in the presence of F-actin. These results suggest that the N-terminal PH-like domain plays a critical role in F-actin binding and F-actin-mediated activation of the cofilin-phosphatase activity of SSH1.

Isolation, Synthesis, and Biological Activity of Chlorinated Alkylresorcinols from Dictyostelium Cellular Slime Molds.

Eight chlorinated alkylresorcinols, monochasiol A-H (1-8), were isolated from the fruiting bodies of Dictyostelium monochasioides. Compounds 1-8 were synthesized to confirm their structures and to obtain sufficient material for performing biological tests. Monochasiol A (1) selectively inhibited the concanavalin A-induced interleukin-2 production in Jurkat cells, a human T lymphocyte cell line. Monochasiols were biogenetically synthesized by the combination of biosynthetic enzymes relating to the principal polyketides, MPBD and DIF-1, produced by Dictyostelium discoideum.

Biological Activities of Novel Derivatives of Differentiation-Inducing Factor 3 from Dictyostelium discoideum.

Differentiation-inducing factor-3 (DIF-3; 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one), which is found in the cellular slime mold Dictyostelium discoideum, is a potential candidate compound for the development of new medicines; DIF-3 and its derivatives possess several beneficial biological activities, including anti-tumor, anti-Trypanosoma cruzi, and immunoregulatory effects. To assess the relationship between the biological activities of DIF-3 and its chemical structure, particularly in regard to its alkoxy group and the length of the alkyl chains at the acyl group, we synthesized two derivatives of DIF-3, 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)octan-1-one (DIF-3(+3)) and 1-(3-chloro-2,6-dihydroxy-4-butoxyphenyl)-hexan-1-one (Hex-DIF-3), and investigated their biological activities in vitro. At micro-molar levels, DIF-3(+3) and Hex-DIF-3 exhibited strong anti-proliferative effects in tumor cell cultures, but their anti-T. cruzi activities at 1 µM in vitro were not as strong as those of other known DIF derivatives. In addition, Hex-DIF-3 at 5 µM significantly suppressed mitogen-induced interleukin-2 production in vitro in Jurkat T cells. These results suggest that DIF-3(+3) and Hex-DIF-3 are promising leads for the development of anti-cancer and immunosuppressive agents.

Mogamulizumab, an anti-CCR4 antibody, targets human T-lymphotropic virus type 1-infected CD8+ and CD4+ T cells to treat associated myelopathy.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) can cause chronic spinal cord inflammation, known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since CD4(+)CCR4(+) T cells are the main HTLV-1 reservoir, we evaluated the defucosylated humanized anti-CCR4 antibody mogamulizumab as a treatment for HAM/TSP. METHODS: We assessed the effects of mogamulizumab on peripheral blood mononuclear cells from 11 patients with HAM/TSP. We also studied how CD8(+) T cells, namely CD8(+) CCR4(+) T cells and cytotoxic T lymphocytes, are involved in HTLV-1 infection and HAM/TSP pathogenesis and how they would be affected by mogamulizumab. RESULTS: Mogamulizumab effectively reduced the HTLV-1 proviral load (56.4% mean reduction at a minimum effective concentration of 0.01 µg/mL), spontaneous proliferation, and production of proinflammatory cytokines, including interferon γ (IFN-γ). Like CD4(+)CCR4(+) T cells, CD8(+)CCR4(+) T cells from patients with HAM/TSP exhibited high proviral loads and spontaneous IFN-γ production, unlike their CCR4(-) counterparts. CD8(+)CCR4(+) T cells from patients with HAM/TSP contained more IFN-γ-expressing cells and fewer interleukin 4-expressing cells than those from healthy donors. Notably, Tax-specific cytotoxic T lymphocytes that may help control the HTLV-1 infection were overwhelmingly CCR4(-). CONCLUSIONS: We determined that CD8(+)CCR4(+) T cells and CD4(+)CCR4(+) T cells are prime therapeutic targets for treating HAM/TSP and propose mogamulizumab as a new treatment.

Development of novel DIF-1 derivatives that selectively suppress innate immune responses.

The multiple pharmacological activities of differentiation-inducing factor-1 (DIF-1) of the cellular slime mold Dictyostelium discoideum led us to examine the use of DIF-1 as a 'drug template' to develop promising seed compounds for drug discovery. DIF-1 and its derivatives were synthesized and evaluated for their regulatory activities in innate immune responses. We found two new derivatives (4d and 5e) with highly selective inhibitory activities against production of the antimicrobial peptide attacin in Drosophila S2 cells and against production of interleukin-2 in Jurkat cells.

Activation of cytosolic Slingshot-1 phosphatase by gelsolin-generated soluble actin filaments.

Slingshot-1 (SSH1) is a protein phosphatase that dephosphorylates and activates cofilin, an actin-severing and -disassembling protein. SSH1 is bound to and activated by F-actin, but not G-actin. SSH1 is accumulated in the F-actin-rich lamellipodium but is also diffusely distributed in the cytoplasm. It remains unknown whether SSH1 is activated by soluble (low-level polymerized) actin filaments in the cytoplasm. In this study, we show that SSH1 binds to gelsolin via actin filaments in the cytosolic fraction. Gelsolin promoted solubilization of actin filaments and SSH1 in cell-free assays and in cultured cells. SSH1 was activated by gelsolin-generated soluble actin filaments. Furthermore, gelsolin enhanced cofilin dephosphorylation in neuregulin-stimulated cells. Our results suggest that cytosolic SSH1 forms a complex with gelsolin via soluble actin filaments and is activated by gelsolin-generated soluble actin filaments and that gelsolin promotes stimulus-induced cofilin dephosphorylation through increasing soluble actin filaments, which support SSH1 activation in the cytoplasm.

Large-Scale Whole-Genome Analysis of HTLV-1-Associated Myelopathy Identified Hereditary Spastic Paraplegias.

Objectives: Distinguishing human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy from hereditary spastic paraplegia in patients infected with HTLV-1 is challenging due to overlapping clinical symptoms. The aim of this study was to explore the possibility that hereditary spastic paraplegia is inherently present in patients diagnosed with HTLV-1-associated myelopathy. Methods: We performed whole-genome sequencing on 315 unrelated patients registered in the HTLV-1-Associated Myelopathy patient registry "HAM-net," from 2013 to 2022 in Japan. CSF inflammatory biomarkers, including CXCL10, were measured. Results: We identified 5 patients with pathogenic variants in the genes RTN2, SPAST, VCP, and UBAP1, which are the known causes of hereditary spastic paraplegia. These patients had no family history of hereditary spastic paraplegia. The levels of CSF inflammatory biomarkers were lower than expected in these patients, compared with disease severity. Discussion: Genetic analysis is useful for the differentiation of hereditary spastic paraplegia patients from HTLV-1-associated myelopathy patients, especially for the patients with low levels of CSF inflammatory markers. Here we report the presence of hereditary spinal cord diseases in patients diagnosed with HTLV-1-associated myelopathy and provides evidence that genetic analysis would be helpful in the diagnostic workflow.

Dictyostelium Differentiation-inducing Factor Derivatives Reduce the Glycosylation of PD-L1 in MDA-MB-231 Human Breast Cancer Cells.

Objectives: Triple-negative breast cancer (TNBC) is a metastatic and intractable cancer with limited treatment options. Refractory cancer cells often express the immune checkpoint molecules programmed death-ligand 1 (PD-L1) and PD-L2, which inhibit the anticancer effects of T cells. Differentiation-inducing factors, originally found in Dictyostelium discoideum, and their derivatives possess strong antiproliferative activity, at least in part by reducing cyclin D1 expression in various cancer cells, but their effects on PD-L1/PD-L2 have not been examined. In this study, we investigate the effects of six DIF compounds (DIFs) on the expression of PD-L1/PD-L2 and cyclin D1/D3 in MDA-MB-231 cells, a model TNBC cell line. Methods: MDA-MB-231 cells were incubated for 5 or 15 h with or without DIFs, and the mRNA expression of cyclin D1, PD-L1, and PD-L2 were assessed by quantitative polymerase chain reaction (qPCR). Whereas, MDA-MD-231 cells were incubated for 12 or 24 h with or without DIFs, and the protein expression of cyclins D1 and D3, PD-L1, and PD-L2 were assessed by Western blotting. Results: As expected, some DIFs strongly reduced cyclin D1/D3 protein expression in MDA-MB-231 cells. Contrary to our expectation, DIFs had little effect on PD-L1 mRNA expression or increased it transiently. However, some DIFs partially reduced glycosylated PD-L1 and increased non-glycosylated PD-L1 in MDA-MB-231 cells. The level of PD-L2 was very low in these cells. Conclusions: Since PD-L1 glycosylation plays an important role in preventing T cells from attacking cancer cells, such DIFs may promote T cell attack on cancer cells in vivo.

The function of cruciate ligaments in bi-cruciate retaining Total knee arthroplasty with asymmetrical design.

BACKGROUND: Bi-cruciate retaining total knee arthroplasty with an asymmetrical design may improve knee function and clinical outcomes. This study aimed to compare the kinematics, anteroposterior laxity, and in situ forces of the anterior and posterior cruciate ligaments of knees subjected to this treatment with those of healthy knees. METHODS: Seven fresh-frozen cadaveric knees were tested using a robotic/universal force-moment sensor system. The kinematics during passive flexion-extension motion and anteroposterior laxity for native knee, treated knee, and treated knee with cruciate ligament transection states were investigated. The motions of the intact and treated knees during each test were repeated after anterior/posterior cruciate ligament transection to calculate the in situ force in the ligaments. FINDINGS: The screw-home movement of normal knees disappeared after treatment. The in situ force of the anterior cruciate ligament in treated knees was higher than that in intact knees at ˃15° during flexion and at 60° and 90° against an anterior force. The in situ force of the posterior cruciate ligament in treated knees was higher at 0°, 15°, and 30° during flexion and at all flexion angles against a posterior force. INTERPRETATION: The screw-home movement of normal knees decreased, and the in situ force of the anterior and posterior cruciate ligaments increased after treatment.

EZH1/2 dual inhibitors suppress HTLV-1-infected cell proliferation and hyperimmune response in HTLV-1-associated myelopathy.

Background: Human T-cell leukemia virus type 1 (HTLV-1) causes HTLV-1-associated myelopathy (HAM), adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated uveitis, and pulmonary diseases. Although both HAM and ATL show proliferation of infected cells, their pathogeneses are quite different. In particular, the pathogenesis of HAM is characterized by hyperimmune responses to HTLV-1-infected cells. Recently, we demonstrated the overexpression of histone methyltransferase EZH2 in ATL cells and the cytotoxic effects of EZH2 inhibitors and EZH1/2 dual inhibitors on these cells. However, these phenomena have never been studied in HAM. Furthermore, what effect these agents have on the hyperimmune response seen in HAM is completely unknown. Methods: In this study, we investigated histone methyltransferase expression levels in infected cell populations (CD4+ and CD4+CCR4+ cells) from patients with HAM using microarray and RT-qPCR analyses. Next, using an assay system that utilizes the spontaneous proliferation characteristic of peripheral blood mononuclear cells derived from patients with HAM (HAM-PBMCs), we investigated the effects of EZH2 selective inhibitors (GSK126 and tazemetostat) and EZH1/2 dual inhibitors (OR-S1 and valemetostat, also known as DS-3201), particularly on cell proliferation rate, cytokine production, and HTLV-1 proviral load. We also examined the effect of EZH1/2 inhibitors on the proliferation of HTLV-1-infected cell lines (HCT-4 and HCT-5) derived from patients with HAM. Results: We found elevated expression of EZH2 in CD4+ and CD4+CCR4+ cells from patients with HAM. EZH2 selective inhibitors and EZH1/2 inhibitors significantly inhibited spontaneous proliferation of HAM-PBMC in a concentration-dependent manner. The effect was greater with EZH1/2 inhibitors. EZH1/2 inhibitors also reduced the frequencies of Ki67+ CD4+ T cells and Ki67+ CD8+ T cells. Furthermore, they reduced HTLV-1 proviral loads and increased IL-10 levels in culture supernatants but did not alter IFN-γ and TNF-α levels. These agents also caused a concentration-dependent inhibition of the proliferation of HTLV-1-infected cell lines derived from patients with HAM and increased annexin-V(+)7-aminoactinomycin D(-) early apoptotic cells. Conclusion: This study showed that EZH1/2 inhibitors suppress HTLV-1-infected cell proliferation through apoptosis and the hyperimmune response in HAM. This indicates that EZH1/2 inhibitors may be effective in treating HAM.

A double mutant between fission yeast telomerase and RecQ helicase is sensitive to thiabendazole, an anti-microtubule drug.

In the fission yeast Schizosaccharomyces pombe, deletion of trt1(+) causes gradual telomere shortening, while deletion of pot1(+) causes rapid telomere loss. The double mutant between pot1 and RecQ helicase rqh1 is synthetically lethal. We found that the trt1 rqh1 double mutant was not synthetically lethal. The chromosome end fragments in both the trt1Δ rqh1Δ and the trt1Δ rqh1-hd (helicase dead) double mutants did not enter a pulsed-field electrophoresis gel. Both the trt1Δ rqh1Δ and the trt1Δ rqh1-hd double mutants were sensitive to the anti-microtubule drug thiabendazole. Moreover, the trt1Δ rqh1-hd double mutant displayed RPA foci on the chromosome bridge at high frequency in M phase cells. These phenotypes are very similar to that of the pot1Δ rqh1-hd double mutant, in which recombination intermediates accumulate at the chromosme ends in the M phase. These results suggest that the entangled chromosome ends, most likely recombination intermediates, are present in the M phase in the trt1Δ rqh1-hd double mutant.

Effect of Accelerated Rehabilitation on Early Return to Sport After Arthroscopic Ankle Lateral Ligament Repair.

Background: Although the minimal invasiveness of arthroscopic ankle lateral ligament repair (ALLR) means that an early return to sporting activities can be anticipated, studies have described postoperative cast immobilization and the avoidance of weightbearing for a certain period. Accelerated rehabilitation may be helpful for an early return to sport. Purpose: To investigate clinical outcomes of ALLR and accelerated rehabilitation with a minimum duration of postoperative ankle immobilization and proactive early weightbearing. Study Design: Case series; Level of evidence, 4. Methods: This study investigated 23 ankles of 22 patients (11 men, 11 women; mean age, 38.7 years) who underwent ALLR for chronic lateral ankle instability. Postoperative management included the avoidance of weightbearing until postoperative day 3, after which full weightbearing walking with a brace was permitted. The objective was to return to competitive sport 8 weeks after surgery. The following were evaluated: pre- and postoperative instability and pain symptoms, ankle range of motion, anterior drawer distance on stress radiograph, anterior translation measured with a capacitance-type strain sensor, the Ankle-Hindfoot Scale from the Japanese Society for Surgery of the Foot, and the SAFE-Q (Self-Administered Foot Evaluation Questionnaire). Results: Two male patients dropped out and were excluded from analysis. Postoperatively, instability and pain resolved or improved in all patients. There was no significant postoperative change in range of motion. There were significant pre- to postoperative improvements in talar tilt angle (from 12.2°-5.6°, P < .01), anterior drawer distance (8.2-4.4 mm, P < .01), and anterior translation (10.5-4.6 mm, P < .01) as well as the Ankle-Hindfoot Scale score (68.8-96.8, P < .01) and all subscales of the SAFE-Q (P ≤ .01 for all). Complete return to sport was achieved by 75% of the patients at 8 weeks postoperatively. Conclusion: When accelerated rehabilitation with proactive weightbearing exercises was implemented from postoperative day 3 without ankle immobilization after ALLR, there were significant improvements in objective assessments of ankle stability and clinical scores, and as many as 75% of the patients were able to make a complete return to sport within 8 weeks.