Conquer coronary artery perforation with magic hands.

Coronary artery perforation (CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.

How robot-assisted gait training affects gait ability, balance and kinematic parameters after stroke: a systematic review and meta-analysis.

INTRODUCTION: Gait ability is often cited by stroke survivors. Robot-assisted gait training (RAGT) can help stroke patients with lower limb motor impairment regain motor coordination. EVIDENCE ACQUISITION: PubMed, Cochrane Library, Embase were systematically searched until September 2023, to identify randomized controlled trials presenting: stroke survivors as participants; RAGT as intervention; conventional rehabilitation as a comparator; gait assessment, through scales or quantitative parameters, as outcome measures. EVIDENCE SYNTHESIS: Twenty-seven publications involving 1167 patients met the inclusion criteria. Meta-analysis showed no significant differences in speed, cadence, spatial symmetry, and changes in joint mobility angles between the RAGT group and the control group. In addition, RAGT was associated with changes in affected side step length (SMD=0.02, 95% CI: 0.01, 0.03; P<0.0001), temporal symmetry (SMD=-0.38, 95% CI: -0.6, -0.16; P=0.0006], Six-Minute Walk Test (SMD=25.14, 95% CI: 10.19, 40.09; P=0.0010] and Functional Ambulation Categories (SMD=0.32, 95% CI: 0.01, 0.63; P=0.04). According to the PEDro scale, 19 (70.4%) studies were of high quality and eight were of moderate quality (29.6%). CONCLUSIONS: Taken together, the review synthesis showed that RAGT might have a potential role in the recovery of walking dysfunction after stroke. However, its superiority over conventional rehabilitation requires further research. Additionally, it may provide unexpected benefits that the effects of RAGT with different types or treatment protocols were further compared.

Noninvasive Stereotactic Radiotherapy for PADN in an Acute Canine Model of Pulmonary Arterial Hypertension.

This study assesses the feasibility, safety, and effectiveness of noninvasive stereotactic body radiotherapy (SBRT) as an approach for pulmonary artery denervation in canine models. SBRT with CyberKnife resulted in reduced mean pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance, and insignificantly increased cardiac output. In comparison to the control group, serum norepinephrine levels at 1 month and 6 months were significantly lower in the CyberKnife group. Computed tomography, pulmonary angiography, and histology analysis revealed that SBRT was associated with minimal collateral damage.

Editorial Commentary: Meniscal Allograft Transplantation Results in Both Pain Relief and Chondroprotection.

Meniscal allograft transplantation (MAT) effectively alleviates symptoms of the meniscus deficiency. Thus, MAT is a widely accepted and recommended treatment for individuals with unicompartmental pain due to meniscus deficiency. Long-term follow-up studies have indicated that MAT yields favorable clinical outcomes, demonstrating high survivorship and low rates of serious complications. In addition, the ability of MAT to function akin to the native meniscus and shield the knee cartilage from osteoarthritis has been a subject of ongoing investigation, and recent direct magnetic resonance imaging evidence shows long-term chondroprotection following MAT. Cartilage lesions worsen during the meniscus deficiency period. Consequently, delaying MAT until patients become more symptomatic may lead to poor outcomes and low graft survivorship due to concomitant cartilage lesions. These findings prompt a reevaluation of the purpose and timing of MAT decisions for meniscectomy patients, suggesting a more proactive approach to recommending MAT, particularly for patients at high risk of postmeniscectomy syndrome and osteoarthritis progression.

Comparing the EU and Chinese carbon trading market operations and their spillover effects.

A carbon trading market (CTM) policy for trading carbon dioxide emission rights as a commodity was created to reduce greenhouse gas emissions. CTMs operate differently in different countries and regions, and their interactions deserve an in-depth study. This study focused on the world's largest CTM, the European Union (EU), and the CTM of China, largest carbon-emitting country. First, we evaluate the liquidity and volatility of the two CTMs. Subsequently, the VAR model is used to explore the mean spillover effect between the two markets and the BEKK-GARCH model is used to explore the volatility spillover effect between the two markets. The study concludes that: (1) The liquidity of China's CTM is better than that of the EU's CTM. (2) Both the EU and Chinese CTMs are unstable, but the volatility of the Chinese CTM is lower than that of the EU CTM. (3) Price changes in the EU and Hubei CTMs have a mutual influence. (4) There are interactions between the market fluctuations of the EU CTM and the Shanghai CTM and those of the EU CTM and the Hubei CTM. The results of this study have implications for the construction and development of CTMs in the EU and China.

A Deep Learning Model Enhances Clinicians' Diagnostic Accuracy to More Than 96% for Anterior Cruciate Ligament Ruptures on Magnetic Resonance Imaging.

PURPOSE: To develop a deep learning model to accurately detect anterior cruciate ligament (ACL) ruptures on magnetic resonance imaging (MRI) and to evaluate its effect on the diagnostic accuracy and efficiency of clinicians. METHODS: A training dataset was built from MRIs acquired from January 2017 to June 2021, including patients with knee symptoms, irrespective of ACL ruptures. An external validation dataset was built from MRIs acquired from January 2021 to June 2022, including patients who underwent knee arthroscopy or arthroplasty. Patients with fractures or prior knee surgeries were excluded in both datasets. Subsequently, a deep learning model was developed and validated using these datasets. Clinicians of varying expertise levels in sports medicine and radiology were recruited, and their capacities in diagnosing ACL injuries in terms of accuracy and diagnosing time were evaluated both with and without artificial intelligence (AI) assistance. RESULTS: A deep learning model was developed based on the training dataset of 22,767 MRIs from 5 centers and verified with external validation dataset of 4,086 MRIs from 6 centers. The model achieved an area under the receiver operating characteristic curve of 0.987 and a sensitivity and specificity of 95.1%. Thirty-eight clinicians from 25 centers were recruited to diagnose 3,800 MRIs. The AI assistance significantly improved the accuracy of all clinicians, exceeding 96%. Additionally, a notable reduction in diagnostic time was observed. The most significant improvements in accuracy and time efficiency were observed in the trainee groups, suggesting that AI support is particularly beneficial for clinicians with moderately limited diagnostic expertise. CONCLUSIONS: This deep learning model demonstrated expert-level diagnostic performance for ACL ruptures, serving as a valuable tool to assist clinicians of various specialties and experience levels in making accurate and efficient diagnoses. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

Artificial intelligence suppression as a strategy to mitigate artificial intelligence automation bias.

BACKGROUND: Incorporating artificial intelligence (AI) into clinics brings the risk of automation bias, which potentially misleads the clinician's decision-making. The purpose of this study was to propose a potential strategy to mitigate automation bias. METHODS: This was a laboratory study with a randomized cross-over design. The diagnosis of anterior cruciate ligament (ACL) rupture, a common injury, on magnetic resonance imaging (MRI) was used as an example. Forty clinicians were invited to diagnose 200 ACLs with and without AI assistance. The AI's correcting and misleading (automation bias) effects on the clinicians' decision-making processes were analyzed. An ordinal logistic regression model was employed to predict the correcting and misleading probabilities of the AI. We further proposed an AI suppression strategy that retracted AI diagnoses with a higher misleading probability and provided AI diagnoses with a higher correcting probability. RESULTS: The AI significantly increased clinicians' accuracy from 87.2%±13.1% to 96.4%±1.9% (P < .001). However, the clinicians' errors in the AI-assisted round were associated with automation bias, accounting for 45.5% of the total mistakes. The automation bias was found to affect clinicians of all levels of expertise. Using a logistic regression model, we identified an AI output zone with higher probability to generate misleading diagnoses. The proposed AI suppression strategy was estimated to decrease clinicians' automation bias by 41.7%. CONCLUSION: Although AI improved clinicians' diagnostic performance, automation bias was a serious problem that should be addressed in clinical practice. The proposed AI suppression strategy is a practical method for decreasing automation bias.

Medial meniscus posterior root tears and partial meniscectomy significantly increase stress in the knee joint during dynamic gait.

PURPOSE: As a simple and invasive treatment, arthroscopic medial meniscal posterior horn resections (MMPHRs) can relieve the obstructive symptoms of medial meniscus posterior root tears (MMPRTs) but with the risk of aggravating biomechanical changes of the joint. The aim of this study was to analyze dynamic simulation of the knee joint after medial meniscus posterior root tear and posterior horn resection. METHODS: This study established static and dynamic models of MMPRTs and MMPHRs on the basis of the intact medial meniscus model (IMM). In the finite element analysis, the three models were subjected to 1000 N axial static load and the human walking gait load defined by the ISO14243-1 standard to evaluate the influence of MMPRTs and MMPHRs on knee joint mechanics during static standing and dynamic walking. RESULTS: In the static state, the load ratio of the medial and lateral compartments remained nearly constant (2:1), while in the dynamic state, the load ratio varied with the gait cycle. After MMPHRs, at 30% of the gait cycle, compared with the MMPRTs condition, the maximum von Mises stress of the lateral meniscus (LM) and the lateral tibial cartilage (LTC) were increased by 166.0% and 50.0%, respectively, while they changed by less than 5% during static analysis. The maximum von Mises stress of the medial meniscus (MM) decreased by 55.7%, and that of the medial femoral cartilage (MFC) increased by 53.5%. CONCLUSION: After MMPHRs, compared with MMPRTs, there was no significant stress increase in articular cartilage in static analysis, but there was a stress increase and concentration in both medial and lateral compartments in dynamic analysis, which may aggravate joint degeneration. Therefore, in clinical treatments, restoring the natural structure of MMPRTs is first recommended, especially for physically active patients.

Meniscal allograft transplantation in discoid meniscus patients achieves good clinical outcomes and superior chondroprotection compared to meniscectomy in the long term.

PURPOSE: To compare the long-term clinical and radiological results of meniscal allograft transplantation (MAT) for discoid lateral meniscus (DLM) patients with MAT for non-discoid lateral meniscus patients and meniscectomy (ME) for DLM patients and, thus, to determine whether DLM patients are suitable candidates for MAT. METHODS: Eight MAT cases in DLM patients were identified (discoid MAT group), six MAT cases in non-discoid lateral meniscus patients (non-discoid MAT group) and ten total meniscectomy cases in DLM patients (discoid ME group) were matched as controls. Subjective evaluations, postoperative radiography and magnetic resonance imaging (MRI) were conducted at 5 years and 10-14 years, respectively. Joint degeneration was evaluated by the Kellgren-Lawrance (KL) grade and joint space width (JSW). MRI with T2 mapping sequences was used to quantitatively evaluate degeneration of the joint cartilage and shrinkage of the allografts. Student's t test was used to compare quantitative variables and the Mann‒Whitney U test was used to compare categorical variables. RESULTS: There was no difference in Lysholm, IKDC, Tegner or VAS scores amongst the discoid MAT, non-discoid MAT and discoid ME groups at the final follow-up. No revision surgery was performed in any MAT patient. The JSW narrowing in the discoid MAT group was better than that in the discoid ME group (0.8 ± 0.4 mm vs. 2.1 ± 1.3 mm, p = 0.012) and worse than that in the non-discoid MAT group (0.1 ± 0.1 mm, p = 0.003). The KL progression of the discoid MAT group was less than that of the discoid ME group (1.3 ± 0.7 vs. 2.3 ± 0.9, p = 0.034). The discoid ME group had worse cartilage lesion progression than the discoid MAT and non-discoid MAT groups. The allograft width of the DLM patients shrank more than that of the non-discoid patients at the meniscus midbody (3.6 ± 0.9 mm vs. 6.2 ± 1.9 mm, p = 0.015). CONCLUSION: Compared to meniscectomy, MAT achieved similar long-term symptom relief and superior chondroprotection in discoid meniscus patients. Despite more graft shrinkage, the outcomes of MAT in discoid meniscus patients were comparable to those in non-discoid meniscus patients. Therefore, DLM patients may be suitable candidates for MAT procedures. LEVEL OF EVIDENCE: Level III.

Atrial myocyte-derived exosomal microRNA contributes to atrial fibrosis in atrial fibrillation.

BACKGROUND: Atrial fibrosis plays a critical role in the development of atrial fibrillation (AF). Exosomes are a promising cell-free therapeutic approach for the treatment of AF. The purposes of this study were to explore the mechanisms by which exosomes derived from atrial myocytes regulate atrial remodeling and to determine whether their manipulation facilitates the therapeutic modulation of potential fibrotic abnormalities during AF. METHODS: We isolated exosomes from atrial myocytes and patient serum, and microRNA (miRNA) sequencing was used to analyze exosomal miRNAs in exosomes derived from atrial myocytes and patient serum. mRNA sequencing and bioinformatics analyses corroborated the key genes that were direct targets of miR-210-3p. RESULTS: The miRNA sequencing analysis identified that miR-210-3p expression was significantly increased in exosomes from tachypacing atrial myocytes and serum from patients with AF. In vitro, the miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis in atrial fibroblasts. Accordingly, miR-210-3p knock out (KO) reduced the incidence of AF and ameliorated atrial fibrosis induced by Ang II. The mRNA sequencing analysis and dual-luciferase reporter assay showed that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is a potential target gene of miR-210-3p. The functional analysis suggested that GPD1L regulated atrial fibrosis via the PI3K/AKT signaling pathway. In addition, silencing GPD1L in atrial fibroblasts induced cell proliferation, and these effects were reversed by a PI3K inhibitor (LY294002). CONCLUSIONS: Atrial myocyte-derived exosomal miR-210-3p promoted cell proliferation and collagen synthesis by inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may be a novel target to ameliorate atrial fibrosis in patients with AF.

An All-Inside Repair Technique for Unstable Type-IV Lateral Meniscal Posterior Root Tear.

Lateral meniscal posterior root tears are defined as tears of meniscus within 9 mm from the bony root attachment. Unrepaired root tears significantly compromise the biomechanical functions of the meniscus, resulting in early and accelerated osteoarthritis. Several authors have described various techniques to reattach the posterior root of the lateral meniscus, and decent short-term results have been observed. Although most previous techniques are capable of repairing radial root tears, difficulties are encountered when repairing oblique type IV tears. In this technique note, the author describes an efficient side-to-side repair technique using the FAST-FIX system, which is practical in repairing the type IV tears of the lateral meniscus. This technique includes certain sequence of the stitches and skills of controlling the root remnant, which makes it easy to penetrate the meniscus and to achieve anatomic repair.

The immediate meniscal allograft transplantation achieved better chondroprotection and less meniscus degeneration than the conventional delayed transplantation in the long-term.

PURPOSE: The purpose of this study was to compare the long-term clinical and radiological outcomes between the immediate and delayed meniscus allograft transplantation (MAT). METHODS: Nine menisci were transplanted immediately after total meniscectomy (immediate group, IM), and 10 menisci were delayed transplanted in patients with the median of 35 months (range 9-92 months) after total meniscectomy (delayed group, DE). Patient's subjective clinical outcomes including VAS, IKDC, Lysholm and Tegner scores as well as muscle strength measures were compared. Joint degeneration was evaluated by both radiographs to assess joint space width narrowing, Kellegren-Lawrence (KL) grade and MRI with T2 mapping sequences to quantitatively analyze both cartilage and meniscal allograft degeneration. RESULTS: The median follow-up time was 10.8 years (range 10-14 years). The IKDC (IM vs DE, 89.8 vs 80.9, n.s.) and Lysholm scores (IM vs DE, 87.7 vs 78.0, n.s.) were close in two groups, while the IM group showed slightly lower VAS (IM vs DE, 0.2 vs 1.5, p = 0.031), higher Tegner score (IM vs DE, 7 vs 3.5 p = 0.021) and better quadriceps muscle strength. The IM group had less joint space narrowing (IM vs DE, 0.35 mm vs 0.71 mm, n.s.), less KL grade progression (IM vs DE, 0.6 vs 1.7, p = 0.041) on radiographs and less chondral lesions development on MRIs (Cartilage Degeneration Index, IM vs DE, 252 vs 2038, p = 0.025). All meniscal grafts exhibited degeneration by showing grade 3 signal on MRI, and 4 (4/9) in the IM group and 8 (8/10) cases in the DE group. The T2 value of cartilage and meniscal allograft in the IM group was close to that of the healthy control and was significantly lower than that of the DE group. CONCLUSION: Compared to the conventional delayed MAT, the immediate MAT achieved better cartilage and meniscus protection in the long-term, while its superiority in patient-reported outcomes was limited. LEVEL OF EVIDENCE: IV.

Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome.

AIMS: Ageing is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF. METHODS AND RESULTS: Herein, by using a faecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NOD-like receptor protein (NLRP)-3 inflammasome, promoting the development of AF, which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then, we conducted cross-sectional clinical studies to explore the effect of ageing on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the ageing phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF. CONCLUSIONS: Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.

The Long-term Chondroprotective Effect of Meniscal Allograft Transplant: A 10- to 14-Year Follow-up Study.

BACKGROUND: The long-term chondroprotective effect of meniscal allograft transplant (MAT) and its superiority over meniscectomy have rarely been reported. HYPOTHESIS: MAT would reduce osteoarthritis (OA) progression when compared with the meniscus-deficient knee. Graft extrusion distance would strongly affect the chondroprotective effect of the MAT. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 17 knees receiving MAT were followed up as the MAT group. The MAT group was further divided into the nonextrusion subgroup (n = 9) and the extrusion subgroup (n = 8) according to 3-mm extrusion on the magnetic resonance imaging (MRI) coronal section. A further 26 consecutive patients receiving meniscectomy in the same period were followed up as the ME group. The healthy control group consisted of healthy contralateral legs chosen from the MAT and ME groups (n = 27). Joint space width (JSW) narrowing was measured on radiographs. Three-dimensional MRI with a T2 mapping sequence was used to quantitatively analyze cartilage degeneration and meniscal allograft extrusion in 5 directions (0°, 45°, 90°, 135°, and 180°). The cartilage degeneration index (CDI) was calculated according to the size and degree of the chondral lesions on MRI scans. The correlation between the CDI increase and the extrusion distance was analyzed. RESULTS: The mean follow-up time was 11.3 years (range, 10-14 years). The MAT group had moderate superiority in chondral protection with less JSW narrowing (0.58 ± 0.66 mm) and CDI increase (1132 ± 1589) compared with the ME group (JSW narrowing: 1.26 ± 1.13 mm, P = .025; CDI increase: 2182 ± 1958, P = .079). The JSW narrowing (0.71 ± 0.80 mm; P = .186) and CDI increase (2004 ± 1965; P = .830) of the extrusion subgroup were close to those of the ME group, demonstrating that a 3-mm extrusion led to complete loss of the meniscal chondroprotective effect. The nonextrusion group had significantly less JSW narrowing (0.48 ± 0.48 mm; P = .042) and CDI increase (358 ± 249; P = .011) than the ME group. The JSW narrowing of the healthy control group was 0.22 ± 0.27 mm. The cartilage T2 values of the extrusion subgroup were similar to those of the ME group, with more OA features, whereas the T2 values of the nonextrusion subgroup were closer to those of the healthy control group. The extrusion distance in the 90° direction (P = .002) and the follow-up time (P = .019) significantly affected the CDI increase in the multivariate regression model. The average extrusion distance in the 45°, 90°, and 135° directions better predicted chondroprotection compared with the other individual directions. CONCLUSION: MAT had moderate advantages in chondroprotection compared with meniscectomy in the long term. Graft extrusion distance strongly affected the chondroprotective effect of MAT. The chondroprotective effect of the nonextruded meniscal allograft was close to that of the native meniscus, whereas the allografts with an extrusion >3 mm completely lost their function after meniscectomy.

Functional Evaluation of Intermediate Coronary Lesions with Integrated Computed Tomography Angiography and Invasive Angiography in Patients with Stable Coronary Artery Disease.

Background and objectives: The hemodynamic evaluation of coronary stenoses undergoes a transition from wire-based invasive measurements to image-based computational assessments. However, fractional flow reserve (FFR) values derived from coronary CT angiography (CCTA) and angiography-based quantitative flow ratio have certain limitations in accuracy and efficiency, preventing their widespread use in routine practice. Hence, we aimed to investigate the diagnostic performance of FFR derived from the integration of CCTA and invasive angiography (FFRCT-angio) with artificial intelligence assistance in patients with stable coronary artery disease (CAD). Methods: Forty stable CAD patients with 67 target vessels (50%-90% diameter stenosis) were included in this single-center retrospective study. All patients underwent CCTA followed by coronary angiography with FFR measurement within 30 days. Both CCTA and angiographic images were combined to generate a three-dimensional reconstruction of the coronary arteries using artificial intelligence. Subsequently, functional assessment was performed through a deep learning algorithm. FFR was used as the reference. Results: FFRCT-angio values were significantly correlated with FFR values (r = 0.81, P < 0.001, Spearman analysis). Per-vessel diagnostic accuracy of FFRCT-angio was 92.54%. Sensitivity and specificity in identifying ischemic lesions were 100% and 88.10%, respectively. Positive predictive value and negative predictive value were 83.33% and 100%, respectively. Moreover, the diagnostic performance of FFRCT-angio was satisfactory in different target vessels and different segment lesions. Conclusions: FFRCT-angio exhibits excellent diagnostic performance of identifying ischemic lesions in patients with stable CAD. Combining CCTA and angiographic imaging, FFRCT-angio may represent an effective and practical alternative to invasive FFR in selected patients.

Prognostic Factors to Determine Survivorship of Meniscal Allograft Transplant: A Systematic Review.

BACKGROUND: There is much room for improvement and optimization of meniscal allograft survivorship. PURPOSE: To understand prognostic factors for survivorship using evidence-based selection criteria in order to identify patients who would best benefit from meniscal allograft transplant (MAT). STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: We conducted this systematic review to analyze prognostic factors for survivorship of MAT. The Cochrane Central Register, PubMed publisher, Embase.com, and Web of Science databases were searched through August 8, 2019. Included studies entailed patients of any age who received MAT with a reported association between prognostic factors and survivorship of the allograft. Two reviewers independently screened all titles and abstracts for eligibility, extracted the data, assessed the risk of bias using the Newcastle-Ottawa Scale, and performed a best-evidence synthesis. RESULTS: The review included 18 studies with a total of 1920 patients. The mean follow-up time was 6.0 years (range, 2.1-11.2 years). A total of 20 prognostic factors were identified and shown to be associated with survivorship of MAT. Strong evidence was found that severe cartilage damage was associated with poor survivorship. Strong evidence was also found showing that sex, knee compartment, surgical side, concomitant anterior cruciate ligament (ACL) reconstruction, and concomitant osteotomy for malalignment had no effect on survivorship. Moderate evidence was found that body mass index (<36), tobacco use, and arthroscopic versus open procedure had no influence on survivorship. Conflicting evidence was found that older age and kissing cartilage lesions (lesions on both the femur and tibia vs on a single side) decreased survivorship. CONCLUSION: Severe cartilage damage decreases the survivorship of MAT. Concomitant ACL reconstruction and osteotomy showed no relationship to survivorship. Many determinants showed conflicting and limited evidence. Older age may be of interest and should be further studied.

Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis.

Periodontitis is an immune inflammatory disease that leads to progressive destruction of bone and connective tissue, accompanied by the dysfunction and even loss of periodontal ligament stem cells (PDLSCs). Pyroptosis mediated by gasdermin-D (GSDMD) participates in the pathogenesis of inflammatory diseases. However, whether pyroptosis mediates PDLSC loss, and inflammation triggered by pyroptosis is involved in the pathological progression of periodontitis remain unclear. Here, we found that PDLSCs suffered GSDMD-dependent pyroptosis to release interleukin-1ß (IL-1ß) during human periodontitis. Importantly, the increased IL-1ß level in gingival crevicular fluid was significantly correlated with periodontitis severity. The caspase-4/GSDMD-mediated pyroptosis caused by periodontal bacteria and cytoplasmic lipopolysaccharide (LPS) dominantly contributed to PDLSC loss. By releasing IL-1ß into the tissue microenvironment, pyroptotic PDLSCs inhibited osteoblastogenesis and promoted osteoclastogenesis, which exacerbated the pathological damage of periodontitis. Pharmacological inhibition of caspase-4 or IL-1ß antibody blockade in a rat periodontitis model lead to the significantly reduced loss of alveolar bone and periodontal ligament damage. Furthermore, Gsdmd deficiency alleviated periodontal inflammation and bone loss in mouse experimental periodontitis. These findings indicate that GSDMD-driven PDLSC pyroptosis and loss plays a pivotal role in the pathogenesis of periodontitis by increasing IL-1ß release, enhancing inflammation, and promoting osteoclastogenesis.

Nitrosonisoldipine is a selective inhibitor of inflammatory caspases and protects against pyroptosis and related septic shock.

Pyroptosis is a type of acute cell death that mainly occurs in immune cells. It is characterized with robust release of inflammatory cytokines and has emerged to play a critical role in the pathogenesis of sepsis-associated immune disorders. In this study, we screened for pyroptotic inhibitors with the ultimate goal to benefit sepsis treatments. Accidentally, we identified that nitrosonisoldipine (NTS), a photodegradation product of calcium channel inhibitor nisoldipine, inhibits noncanonical pyroptosis. Using murine immortalized BM-derived macrophage and human THP-1 cell line, we further discovered that NTS not only inhibits noncanonical pyroptosis mediated by caspase-11 or caspase-4 but also canonical pyroptosis mediated by caspase-1. Mechanistically, NTS directly inhibits the enzyme activities of these inflammatory caspases, and these inhibitory effects persist despite extensive washout of the drug. By contrast, apoptosis mediated by caspase-3/-7 was not affected by NTS. Mice pretreated with NTS intraperitoneally displayed improved survival rate and extended survival time in LPS- and polymicrobe-induced septic models, respectively. In conclusion, NTS is a selective inhibitor of inflammatory caspases that blocks both the noncanonical and canonical pyroptotic pathways. It is safe for intraperitoneal administration and might be used as a prototype to develop drugs for sepsis treatments.

Increased Susceptibility of Atrial Fibrillation Induced by Hyperuricemia in Rats: Mechanisms and Implications.

High levels of serum uric acid is closely associated with atrial fibrillation (AF); nonetheless, the detailed mechanisms remain unknown. Therefore, this work examined the intricate mechanisms of AF triggered by hyperuricemia and the impact of the uricosuric agent benzbromarone on atrial remodeling in hyperuricemic rats. After adjusting baseline serum uric acid levels, a total of 28 healthy male adult Sprague Dawley rats were randomly divided into 4 groups, namely, control (CTR), hyperuricemia (oxonic acid potassium salt, OXO) and benzbromarone (+ BBR), and OXO withdrawal groups. Primary rat cardiomyocytes were cultured with uric acid for 24 h to investigate the direct influence of uric acid on cardiomyocytes. Results revealed that AF vulnerability and AF duration were dramatically greater in hyperuricemic rats (OXO group), while the atrial effective refractory periods (AERPs) were significantly shorter. Meanwhile, BBR treatment and withdrawal of 2% OXO administration remarkably reduced AF inducibility and shortened AF duration. Moreover, abnormal morphology of atrial myocytes, atrial fibrosis, apoptosis, and substantial sympathetic nerve sprouting were observed in hyperuricemic rats. Apoptosis and fibrosis of atria were partly mediated by caspase-3, BAX, TGF-ß1, and α-smooth muscle actin. Uric acid significantly induced primary rat cardiomyocyte apoptosis and fibrosis in vitro. Also, we found that sympathetic nerve sprouting was markedly upregulated in the atria of hyperuricemia rats, and was restored by BRB or absence of OXO administration. In summary, our study confirmed that AF induced by hyperuricemic rats occurred primarily via induction of atrial remodeling, thereby providing a novel potential treatment approach for hyperuricemia-related AF.