Oxygen-Propelled Dual-Modular Microneedles with Dopamine-Enhanced RNA Delivery for Regulating Each Stage of Diabetic Wounds.

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.

Surgical treatment for medium-sized cystic osteochondral lesions of the talus: Autologous osteoperiosteal transplantation provides better clinical outcomes than bone marrow stimulation when cysts are deeper than 6 mm.

PURPOSE: To compare clinical outcomes of autologous osteoperiosteal transplantation versus bone marrow stimulation (BMS) for medium-sized (100-150 mm2) cystic osteochondral lesions of the talus (OLTs) and assess the correlation between patient demographics and outcomes. It was hypothesised that autologous osteoperiosteal transplantation would provide better clinical outcomes than BMS for medium-sized cystic OLTs. METHODS: Patients who underwent autologous osteoperiosteal transplantation or BMS for medium-sized cystic OLTs between 2014 and 2019 were retrospectively evaluated. According to their characteristics, a 1:1 propensity-score matching was performed and 33 pairs of patients were matched. The visual analogue scale, American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot Ankle Outcome Score (FAOS) and Ankle Activity Score were collected preoperatively and at the last follow-up. In addition, a general linear model analysis was performed between patient demographics and clinical outcomes in two groups separately to detect potential risk factors. RESULTS: Finally, 28 patients in the grafted group and 27 patients in the BMS group completed the follow-up and were enrolled with a mean follow-up period of 63.5 ± 13.9 months. Both groups showed significant improvement in all patient-reported outcomes (p < 0.01). At the final follow-up, no significant differences between groups were found in all postoperative scores except FAOS Pain (p = 0.02). Correlation analysis showed a moderate correlation between cyst depth and the postoperative AOFAS score in the BMS group (r = -0.48, p = 0.01). Based on the regression line, the patients in the BMS group with a cyst deeper than 6 mm showed a lower AOFAS score than the mean score (88.7 ± 9.5) of the grafted group. CONCLUSION: Autologous osteoperiosteal transplantation and BMS are both safe and effective for medium-sized cystic OLTs. However, autologous osteoperiosteal transplantation is expected to provide better clinical outcomes than BMS when the cysts are deeper than 6 mm. LEVEL OF EVIDENCE: Level III.

Deciphering Autoimmune Diseases: Unveiling the Diagnostic, Therapeutic, and Prognostic Potential of Immune Repertoire Sequencing.

Autoimmune diseases (AIDs) are immune system disorders where the body exhibits an immune response to its own antigens, causing damage to its own tissues and organs. The pathogenesis of AIDs is incompletely understood. However, recent advances in immune repertoire sequencing (IR-seq) technology have opened-up a new avenue to study the IR. These studies have revealed the prevalence in IR alterations, potentially inducing AIDs by disrupting immune tolerance and thereby contributing to our comprehension of AIDs. IR-seq harbors significant potential for the clinical diagnosis, personalized treatment, and prognosis of AIDs. This article reviews the application and progress of IR-seq in diseases, such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes, to enhance our understanding of the pathogenesis of AIDs and offer valuable references for the diagnosis and treatment of AIDs.

Medial Cystic Osteochondral Lesions of the Talus Exhibited Lower Sports Levels, Higher Cyst Presence Rate, and Inferior Radiological Outcomes Compared With Lateral Lesions Following Arthroscopic Bone Marrow Stimulation.

PURPOSE: To compare the patient-reported outcomes and radiologic outcomes of the patients with medial and lateral cystic osteochondral lesions of the talus (OLTs) following bone marrow stimulation (BMS). METHODS: Patients with cystic OLTs who underwent BMS between January 2016 and February 2021 were retrospectively analyzed, and the minimum follow-up time was more than 24 months. Patients were paired in a 1:1 ratio (medial cystic OLT [MC-OLT]/lateral cystic OLT [LC-OLT]) based on the OLT area within 30 mm2, follow-up within 1 year, age within 5 years, and ligament surgery (yes/no). The visual analog scale and Foot and Ankle Ability Measure (FAAM)-Activities of Daily Life and Sports scores were assessed preoperatively and postoperatively. The magnetic resonance observation of cartilage repair tissue scores and presence of cysts after BMS were also evaluated. Additionally, the receiver operating characteristic curve was performed. RESULTS: The matched patients were divided into the MC-OLT (n = 31, 43.35 ± 12.32 months) and LC-OLT groups (n = 31, 43.32 ± 14.88 months, P = .986). Thirty patients of each group achieved a power of 80% and an α = 0.05 in this study. The MC-OLT group showed significantly less improvement in FAAM-Activities of Daily Life and sports scores (P = .034, P < .001, respectively), lower magnetic resonance observation of cartilage repair tissue scores (80.80 ± 11.91 vs 86.00 ± 8.50, P = .010), and higher presence rate of cysts after BMS (45.16% vs 16.12%, P = .013). Regarding FAAM sports scores, the LC-OLT group had significantly more patients exceeding the minimal clinically important difference (80.64% vs 51.61%, P = .031). Furthermore, an OLT depth of 7.23 mm (sensitivity: 78.6%; specificity: 70.6%) might serve as a cutoff value for predicting the presence of cysts in medial cystic OLTs following BMS. CONCLUSIONS: Medial cystic OLTs exhibited markedly lower sports levels, higher cyst presence rate, and inferior radiologic outcomes following BMS than lateral counterparts. Additionally, an OLT depth of 7.23 mm could be the cutoff value for predicting the presence of cysts regarding medial cystic OLTs after BMS. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Do color enhancement algorithms improve the experience of color-deficient people? An empirical study based on smartphones.

Approximately 8% of the global population experiences color-vision deficiency. It is important to note that "color-vision deficiency" is distinct from "color blindness," as used in this article, which refers to the difficulty in distinguishing certain shades of color. This study explores color enhancement algorithms based on the neural mechanisms of color blindness and color deficiency. The algorithms are then applied to smartphones to improve the user experience (UX) of color-enhancing features in different top-selling smartphone brands with different operating systems (OS). A color-enhancing application program was developed for individuals with color-vision deficiency and compared to two other mature color-enhancing programs found in top-selling smartphones with different mainstream operating systems. The study included both objective and subjective evaluations. The research materials covered three aspects: daily life, information visualization, and videos. Additionally, this research study examines various levels of color enhancement through three dimensions of subjective evaluation: color contrast, color naturalness, and color preference. The results indicate that all color-enhancing features are beneficial for individuals with color-vision deficiencies due to their strong color contrast. The users' color preference is closely linked to color naturalness. The application program preserves the naturalness of colors better than the other two color-enhancing features. The subjective evaluations show similar trends across different operating systems, with differences arising from the use of different color-enhancing algorithms. Therefore, different algorithms may result in different sizes of the color gamut.

Effect of Cigarette Smoking on Postoperative Outcomes After Arthroscopic Bone Marrow Stimulation for Osteochondral Lesions of the Talus.

BACKGROUND: Bone marrow stimulation (BMS) is presently considered first-line surgical treatment for osteochondral lesions of the talus (OLTs); however, some patients still experience pain or dysfunction after surgery, and the reasons for success or failure remain somewhat unclear. This study aimed to investigate the effect of smoking on postoperative outcomes after arthroscopic BMS for OLTs. METHODS: Consecutive patients with OLTs who underwent BMS between January 2017 and January 2020 were included. Smokers were defined as patients who actively consumed cigarettes before surgery and postoperatively, whereas nonsmokers were patients who never smoked. Visual analog scale (VAS), American Orthopaedic Foot & Ankle Society ankle hindfoot score (AOFAS), Karlsson-Peterson, and Tegner scores were assessed preoperatively and at follow-up. Additionally, a general linear model (GLM) was performed, followed by the interaction analysis to explore the potential influence of smoking. RESULTS: The study enrolled 104 patients with a mean follow-up of 30.91 ± 7.03 months, including 28 smokers and 76 nonsmokers. There were no significant differences in patient age (35.2 ± 10.0 years vs 37.6 ± 9.7 years, P = .282) or OLT area (63.7 ± 38.7 mm2 vs 52.8 ± 37.0 mm2, P = .782). Both univariate analysis and GLM revealed that smoking was associated with worse postoperative pain levels, Karlsson-Peterson, and AOFAS scores (P < .05). The interaction analysis showed a significant interaction between smoking and OLT area for postoperative Karlsson-Peterson scores (general ankle function) (P = .031). Simple main effects analysis revealed that the negative effect of smoking on Tegner score significantly increased among patients >32 years old or with OLT area>50 mm2 (P < .05). CONCLUSION: Smoking was associated with worse clinical outcomes following BMS of OLTs. As the size of OLTs increased, the difference in general ankle function between smokers and nonsmokers also increased. Furthermore, smokers who were older than 32 years or had larger OLTs were less likely to resume participation in high-level activities.

Unraveling susceptibility genes: A contemporary overview of autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITDs), including Graves' disease and Hashimoto's thyroiditis, are organ-specific autoimmune disorders characterized by conditions including goiter, autoimmune thyroiditis, hyperthyroidism, and hypothyroidism, which represent the most severe clinical manifestations of AITDs. The prevalence of autoimmune thyroid disorders is on the rise, influenced by increased environmental factors and changes in modern lifestyles. Understanding the pathophysiology of AITDs is crucial for identifying key factors that affect the disease's onset, progression, and recurrence, thereby laying a solid foundation for precise diagnosis and treatment. The development of AITDs involves a complex interplay of environmental influences, immune dysfunctions, and genetic predispositions. Genetic predispositions, in particular, are significant, with numerous genes identified as being linked to AITDs. This article focuses on examining the genes vulnerable to AITDs to deepen our understanding of the relevant genetic contributors, ultimately facilitating the development of effective prevention and treatment methods.

Both arthroscopic one-step Broström-Gould and Lasso-loop stitch techniques achieved favourable clinical outcomes for chronic lateral ankle instability.

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.

Clinical Outcomes and Return to Preinjury Sports After Anatomic Reconstruction With a Gracilis Autograft Versus the Modified Broström Procedure in Patients With Generalized Joint Laxity.

Background: Generalized joint laxity (GJL) is a risk factor for inferior outcomes after the modified Broström procedure for chronic lateral ankle instability, while anatomic reconstruction with tendons is more inclined to be recommended. However, whether anatomic reconstruction could achieve better results than the modified Broström procedure in patients with GJL is unknown. Purpose: To compare clinical outcomes and return to sports between anatomic reconstruction and the modified Broström procedure in patients with GJL. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with GJL (Beighton score ≥4) who underwent either the modified Broström procedure or anatomic reconstruction with gracilis autografts between 2017 and 2020 were reviewed. Included were 19 patients who underwent anatomic reconstruction (reconstruction group) and 49 patients who underwent the modified Broström procedure (MBP group). Clinical outcomes were compared using the Foot and Ankle Outcome Score (FAOS) and the Karlsson score. The rates of return to preinjury level in high-demand sports, sprain recurrence, and range of motion between the 2 groups were also compared. Results: The mean follow-up duration was 38.3 months in the reconstruction group and 43.7 months in the MBP group. The FAOS and Karlsson scores improved significantly after surgery in both groups (P < .001 for all), with the reconstruction group having significantly higher postoperative FAOS-Sports scores (87.9 ± 8.9 vs 80.5 ± 11.6; P = .015) and Karlsson scores (86.9 ± 6.1 vs 82 ± 8.4; P = .025) than the MBP group. The rate of return to preinjury high-demand sports was higher in the reconstruction group than in the MBP group (73.3% vs 38.9%; P = .034). The MBP group had a significantly higher rate of sprain recurrence (22.4% vs 0%; P = .027). More patients reported dorsiflexion restriction in the reconstruction group (n = 4; 21.1%) than in the MBP group (n = 1; 2%) (P = .019); nonetheless, there was no noticeable effect on daily life and sports. Conclusion: Better clinical outcomes, less sprain recurrence, and a higher rate of return to preinjury high-demand sports were found after anatomic reconstruction with free tendons compared with the modified Broström procedure in patients with GJL. Anatomic tendon reconstruction can be recommended for such patients, especially those participating in high-demand sports.

Return to Sport After Anatomic Lateral Ankle Stabilization Surgery for Chronic Ankle Instability: A Systematic Review and Meta-analysis.

BACKGROUND: Chronic lateral ankle instability that develops after ankle sprains has a severe, negative influence on the patient's lower extremity function. Anatomic repair or reconstruction of the lateral ankle ligament is an effective treatment for people with chronic lateral ankle instability who want to regain their preinjury levels of work and sport. PURPOSE: To determine the rate of return to sport (RTS) and related factors after anatomic lateral ankle stabilization (ALAS) surgery. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: Electronic databases including Medline, Embase, the Cochrane Library, and EBSCO Rehabilitation & Sports Medicine Source were searched from the earliest feasible entrance until August 2021. Articles reporting the number of patients who returned to sport after ALAS surgery and analyzing the relevant factors were included. The results were combined using proportion meta-analyses. RESULTS: A total of 25 publications were reviewed, with a total of 1384 participants. Results showed that 95% of patients (95% CI, 91%-99%) returned to any sport, 83% (95% CI, 73%-91%) returned to their preinjury level of sport, and 87% (95% CI, 71%-98%) returned to competitive sport after surgery. The mean time to RTS was 12.45 weeks (95% CI, 10.8-14.1 weeks). Each decade of age increased the likelihood of RTS failure by 6%, and increases in body mass index (BMI) of 5 kg/m2 raised the risk of RTS failure by 4%. The rate of RTS was higher in professional and competitive athletes (93%; 95% CI, 73%-100%) than in recreational athletes (83%; 95% CI, 76%-89%). Analysis showed no differences for arthroscopy versus open surgery, repair versus reconstruction, and early versus late weightbearing. CONCLUSION: In most cases, patients may return to some kind of sport after ALAS surgery, and some patients RTS at their preinjury level. The relative risk of RTS failure increases according to the magnitude of the increase in age and BMI. Elite athletes are more likely to return compared with nonelite athletes.

Avulsion fracture is associated with more pain after anatomic repair procedure for ATFL injury at the talar side.

PURPOSE: To evaluate the clinical outcomes of anatomic repair procedure for chronic anterior talofibular ligament (ATFL) injury at the talar side, and to compare the outcomes between patients with and without concomitant avulsion fractures. It was hypothesized that anatomic repair procedure could produce similarly satisfactory outcomes for those two groups. METHODS: Thirty-nine consecutive patients with chronic ATFL injuries at the talar side who underwent anatomic repair procedure at the department of sports medicine at Peking University Third Hospital between 2013 and 2018, were retrospectively evaluated. The pain visual analogue scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Tegner score, and Foot & Ankle Outcome Score (FAOS) were recorded as the primary outcomes. Time to return to sports (RTS), surgical satisfaction, deficiency of ankle range of motion (ROM), recurrent sprain, and postoperative complications were recorded as the secondary outcomes. Outcomes were compared between patients with (Group A, 16 cases) and without (Group B, 23 cases) concomitant avulsion fractures. RESULTS: The mean follow-up time was 79.4 ± 17.0 and 76.6 ± 18.5 months for Group A and B, respectively. VAS, AOFAS, Tegner, FAOS, and all subscale scores of FAOS were significantly improved in both groups at the final follow up. Patients in group A had inferior postoperative VAS, AOFAS, FAOS, and pain score of FAOS compared to group B (1.1 ± 1.1 vs. 0.4 ± 0.5, 89.1 ± 10.1 vs. 95.2 ± 5.2, 87.2 ± 7.2 vs. 91.5 ± 4.1, and 88.4 ± 11.3 vs. 96.7 ± 3.5, respectively).The mean time to RTS, rate of satisfaction and recurrent sprain had no significant differences between group A and B (6.1 ± 2.8, 93.8%, and 18.8% vs. 5.2 ± 2.2, 100.0%, and 13.0%, respectively), and the rate of ROM deficiency was significantly higher in group A (37.5 vs. 8.7%). Avulsion fracture was identified as an independent risk factor for inferior pain score of FAOS. CONCLUSION: Anatomic repair procedure for chronic ATFL injuries at the talar side produces favourable results for patients with and without avulsion fractures at 5 to 10 years follow-up, however, avulsion fracture is associated with more pain. LEVEL OF EVIDENCE: III.

Landscape of enhancer disruption and functional screen in melanoma cells.

BACKGROUND: The high mutation rate throughout the entire melanoma genome presents a major challenge in stratifying true driver events from the background mutations. Numerous recurrent non-coding alterations, such as those in enhancers, can shape tumor evolution, thereby emphasizing the importance in systematically deciphering enhancer disruptions in melanoma. RESULTS: Here, we leveraged 297 melanoma whole-genome sequencing samples to prioritize highly recurrent regions. By performing a genome-scale CRISPR interference (CRISPRi) screen on highly recurrent region-associated enhancers in melanoma cells, we identified 66 significant hits which could have tumor-suppressive roles. These functional enhancers show unique mutational patterns independent of classical significantly mutated genes in melanoma. Target gene analysis for the essential enhancers reveal many known and hidden mechanisms underlying melanoma growth. Utilizing extensive functional validation experiments, we demonstrate that a super enhancer element could modulate melanoma cell proliferation by targeting MEF2A, and another distal enhancer is able to sustain PTEN tumor-suppressive potential via long-range interactions. CONCLUSIONS: Our study establishes a catalogue of crucial enhancers and their target genes in melanoma growth and progression, and illuminates the identification of novel mechanisms of dysregulation for melanoma driver genes and new therapeutic targeting strategies.

Arthroscopic modified Broström procedure achieved similar favorable short term outcomes to open procedure for chronic lateral ankle instability cases with generalized joint laxity.

PURPOSE: To compare the short-term clinical outcomes of the open versus arthroscopic modified Broström procedure in generalized joint laxity (GJL) patients. METHODS: From January 2018 to January 2020, 64 consecutive patients with chronic lateral ankle instability (CLAI) and GJL (Beighton score ≥ 4) were prospectively enrolled into two groups: those who underwent the open modified Broström procedure (open group, n = 32) and those who underwent the arthroscopic modified Broström procedure (arthroscopic group, n = 32). Patients underwent an open or arthroscopic modified Broström procedure based on the time when they attended the clinic for consultation. All patients were followed-up at 3, 6, 12, and 24 months postoperatively. The clinical outcomes were evaluated using the visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Karlsson score, and the radiographic outcomes were assessed using stress radiography at 24 months postoperatively. The time to return to work and the failure rate were also evaluated and compared. RESULTS: Follow-up was completed for 31 patients in the open group and 30 patients in the arthroscopic group. No significant differences were found between the two groups in terms of demographic characteristics, Beighton score (6.2 ± 1.9 vs. 5.5 ± 1.4, n.s.), or duration of symptoms. There were no significant differences in the functional scores before surgery and at 6, 12 and 24 months postoperatively or in the mean anterior translation of the talus and talar tilt angle on stress radiography at 24 months postoperatively between the open and arthroscopic groups. Compared to the open group, the arthroscopic group showed a significantly earlier return to work (6.8 ± 2.1 vs. 8.1 ± 2.4 weeks, p = 0.006). There was no significant difference in terms of the failure rate between the open and arthroscopic groups (16.1% vs. 23.3%, n.s.). CONCLUSION: Arthroscopic modified Broström procedure achieved similar short-term outcomes to the open procedure for GJL patients. Arthroscopic modified Broström procedure showed an earlier return to work than the open modified Broström procedure and was an alternative to open surgery for CLAI patients with GJL. LEVEL OF EVIDENCE: III. CLINICAL TRIAL REGISTRATION: This study is a prospective study NCT05284188.

Favourable clinical, arthroscopic and radiographic outcomes after autologous osteoperiosteal transplantation for massive medial cystic osteochondral defects of the talus.

PURPOSE: The purpose of this study was to retrospectively evaluate the clinical, arthroscopic and radiological outcomes of autologous osteoperiosteal transplantation for massive cystic osteochondral defects of the talus. METHODS: Cases of autologous osteoperiosteal transplantation for medial massive cystic defects of the talus between 2014 and 2018 were reviewed. The visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, Foot and Ankle Outcome Score (FAOS), and Ankle Activity Scale (AAS) were assessed preoperatively and postoperatively. The Magnetic Resonance Observation of Cartilage Tissue (MOCART) system and the International Cartilage Repair Society (ICRS) score were evaluated after surgery. The ability to return to daily activity and sport, as well as complications, were recorded. RESULTS: Twenty-one patients were available for follow-up, with a mean follow-up of 60.1 ± 11.7 months. All subscales of preoperative FAOS had significant (P < 0.001) improvement at the final follow-up. The mean AOFAS and VAS scores significantly (P < 0.001) improved from 52.4 ± 12.4 preoperatively to 90.9 ± 5.2 at the last follow-up and from 7.9 ± 0.8 to 1.5 ± 0.9, respectively. The mean AAS decreased from 6.0 ± 1.4 preinjury to 1.4 ± 0.9 postinjury and then increased to 4.6 ± 1.4 at the final follow-up (P < 0.001). All 21 patients resumed daily activities after a mean of 3.1 ± 1.0 months. Fifteen patients (71.4%) returned to sports after a mean of 12.9 ± 4.1 months. All patients underwent follow-up MRI with a mean MOCART score of 68.6 ± 5.9. Eleven patients underwent second-look arthroscopy, and the average ICRS was 9.4 ± 0.8. No donor site morbidity was found in any patient during the follow-up. CONCLUSION: Autologous osteoperiosteal transplantation provided favourable clinical, arthroscopic and radiographic outcomes in patients with massive cystic osteochondral defects of the talus during a minimum 3-year follow-up. LEVEL OF EVIDENCE: IV.

Concomitant Subchondral Bone Cysts Negatively Affect Clinical Outcomes Following Arthroscopic Bone Marrow Stimulation for Osteochondral Lesions of the Talus.

PURPOSE: To study the effects of concomitant subchondral bone cysts (SBCs) on prognosis after arthroscopic bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLTs) less than 100 mm2 and to further assess the correlation between cystic OLT area, depth, or volume and postoperative outcomes. METHODS: We retrospectively analyzed consecutive patients with OLTs (<100 mm2) who received BMS between April 2017 and May 2020 with a minimum follow-up of 24 months. Lesion area, depth, and volume were collected on preoperative magnetic resonance imaging. Visual analog scale (VAS), American Orthopedic Foot and Ankle Society, Karlsson-Peterson, Tegner, Foot and Ankle Ability Measure (FAAM)-Activities of Daily Life and Sports scores were assessed before surgery and at the latest follow-up. Additionally, a general linear model (GLM) and a Pearson correlation analysis (PCA) were performed to investigate the effects of concomitant cysts on postoperative results. RESULTS: Eighty-two patients with a mean follow-up of 39.22 ± 12.53 months were divided into non-cyst (n = 45; 39.91 ± 13.03 months) and cyst (n = 37; 38.37 ± 12.02 months) groups. There was no significant difference in the OLT area between the non-cyst and cyst groups (46.98 ± 19.95 mm2 vs 56.08 ± 22.92 mm2; P = .093), but the cyst group showed significantly greater depth (6.06 ± 1.99 mm vs 3.96 ± 1.44 mm; P = .000) and volume (248.26 ± 156.81 mm3 vs 134.58 ± 89.68 mm3; P = .002). The non-cyst group showed significantly more improvement in VAS pain, Karlsson-Peterson, Tegner, and FAAM scores than the cyst group (P < .05). The GLM indicated that SBCs negatively affected VAS pain and Tegner scores (P < .05). For OLTs with cysts, the PCA showed that an area of 90.91 mm2, depth of 7.56 mm, and volume of 428.13 mm3 were potential cutoff values associated with poor outcomes. CONCLUSIONS: The concomitant SBCs negatively affected the prognosis of OLTs after BMS. For OLTs with cysts, an area of 90.91 mm2, depth of 7.56 mm, and volume of 428.13 mm3 were the potential cutoff values associated with poor outcomes after BMS. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Effect of Arthroscopically Confirmed Syndesmotic Widening on Outcome Following Isolated Broström Operation for Chronic Lateral Ankle Instability.

BACKGROUND: Tibiofibular syndesmosis (TFS) widening sometimes is not evident on radiography but can be found under arthroscopy in chronic lateral ankle instability (CLAI). This study aimed to evaluate the effect of TFS widening severity on clinical outcomes and return to activities after isolated Broström operation in CLAI patients and to propose an indication for its surgical intervention. METHODS: A total of 118 CLAI patients undergoing diagnostic ankle arthroscopy and open Broström-Gould operation were included. Based on the middle width of TFS measured under arthroscopy, patients were divided into the TFS-2 group (≤2 mm, n = 44), the TFS-3 group (2-4 mm, n = 42), and the TFS-4 group (≥4 mm, n = 32). The time to return to recreational sport and work, Tegner activity score, and proportion of returning to preinjury sports at the final follow-up were evaluated and compared. Other subjective evaluations included the American Orthopaedic Foot & Ankle Society score, visual analog scale, and Karlsson-Peterson score. RESULTS: Among the 3 groups, the TFS-4 group demonstrated the longest mean time to return to work and recreational sports, with the lowest proportion returning to preinjury sports. The TFS-4 group showed a significantly higher rate of sprain recurrence (12.5%) than the other 2 groups (P =.021). All the other subjective scores significantly improved after the operation without differences among the 3 groups. CONCLUSION: Concomitant severe syndesmotic widening adversely affects the return to activities after Broström operation in CLAI cases. The CLAI patients with a middle TFS width ≥4 mm were associated with delayed return to work and sports, a lower proportion of returning to preinjury sports, and more sprain recurrence, which might require further surgical intervention for syndesmosis in addition to Broström surgery. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Acute Distal Rupture of the Calcaneus-Fibular Ligament Near the Calcaneus Insertion: Magnetic Resonance Imaging for Diagnostic Value and Comparison to Surgical Findings-A Retrospective Case Series Study.

Distal rupture of the calcaneus-fibular ligament (CFL) was unique and important, because it is crucial to diagnose this type of injury before surgical intervention. In the present study, we collected several imaging characteristics based on MRI and tried to determine whether those clues can be used to diagnose distal rupture of CFL specifically and sensitively. Several imaging characteristics based on MRI were collected and used to diagnose and determine the location of CFL injury. All these clues on preoperative MRI were verified by operative findings and postoperative roentgenography. The interobserver agreement for the quality of the MRI images had a p value of .6 (McNemar test) and a Cohen's kappa of 65.2% (confidence interval, 50.5%-79.9%), and the agreement of the 2 observers was categorized as substantial. The sensitivity and specificity of distal rupture of CFL between 2 observers were 76.3%, 91.4% and 72.2%, 85.55%, respectively. The sensitivity and specificity of MRI clues were calculated as follows: hyperintense signal changes (86.1%, 38.6%), peroneal sheath fluid (63.9%, 74.7%), wave or laxity of the ligament (80.6%, 51.8%), fluid exudation around the ligament (80.6%, 51.8%), bone marrow edema on the calcaneus insertion (2.8%, 91.6%), avulsion fracture of the calcaneus (0%, 96.4%), incongruency or disruption of the ligament (69.4%, 77.1%), and exudation on the subtalar joint (52.8%, 71.1%). Preoperative MRI scans are a useful tool to diagnose distal injury of the CFL.

An autoimmune pleiotropic SNP modulates IRF5 alternative promoter usage through ZBTB3-mediated chromatin looping.

Genetic sharing is extensively observed for autoimmune diseases, but the causal variants and their underlying molecular mechanisms remain largely unknown. Through systematic investigation of autoimmune disease pleiotropic loci, we found most of these shared genetic effects are transmitted from regulatory code. We used an evidence-based strategy to functionally prioritize causal pleiotropic variants and identify their target genes. A top-ranked pleiotropic variant, rs4728142, yielded many lines of evidence as being causal. Mechanistically, the rs4728142-containing region interacts with the IRF5 alternative promoter in an allele-specific manner and orchestrates its upstream enhancer to regulate IRF5 alternative promoter usage through chromatin looping. A putative structural regulator, ZBTB3, mediates the allele-specific loop to promote IRF5-short transcript expression at the rs4728142 risk allele, resulting in IRF5 overactivation and M1 macrophage polarization. Together, our findings establish a causal mechanism between the regulatory variant and fine-scale molecular phenotype underlying the dysfunction of pleiotropic genes in human autoimmunity.