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Molian Tang,1,* Zhiqi Chen,1,* Jialu Wang,1 Anqi Song,1 I-Ting Wu,2 Renying Xu1,3 1Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Data & Research Cornerstone Whole Healthcare Organization (C-Who), Inc., Boise, Idaho, USA; 3Department of Nutrition, College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Renying Xu, Department of Clinical Nutrition, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China, Tel +86-021-68383335, Email 721001735@shsmu.edu.cnBackground: The impact of quarantine-induced changes in dietary behavior on weight gain remained unclear. This study aimed to evaluate the association between changes in dietary behavior and body weight during quarantine and to identify the risk factors of weight gain.Methods: This was a pilot observational cross-sectional study. All the potential participants were those who underwent body weight management program in one teaching hospital in China from 26th April 2021 to 31st March 2022. An online self-reported questionnaire was sent to collect information on sex, age, self-reported body weight before and after quarantine, dietary quality, meal time, food consumption, physical activities, and sleep quality. Weight gain was defined as an increase of 1 kilogram or more. The study has been performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee (KY2020-204). The participants were informed about the objectives of the study and electronic informed consent was obtained from each participant.Results: Finally, 79 participants (22.8% male and 77.2% female, aged 33.3 ± 7.1 years) was included in the analysis. During quarantine, the mean body weight gain was 0.8 (interquartile range: − 1.0~3.0) kg. The proportion of weight gain among the participants was 45.6%. Increased cooked white rice (OR=16.93; 95% CI: 2.66– 108.00), convenient food (OR=11.69; 95% CI: 2.00– 68.26), and snack consumption (OR=5.56; 95% CI: 1.08– 28.56), delayed dinner time (OR=6.64; 95% CI: 1.20– 36.74) and house working time less than 30 minutes (OR=12.80; 95% CI: 2.01– 81.44) were risk factors for body weight gain.Conclusion: During the quarantine, weight gain was observed even in participants who were previously on body weight management. Increased consumption of cooked white rice, convenient food, and snack, as well as delayed dinner time and reduced house working time (less than 30 minutes), were found to be associated with body weight gain.Keywords: body weight, physical activity, food consumption, quarantine

Introduction: Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes., Methods: We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model., Results: Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B vs. A (HR=2.21, p=0.041), BCLC stage C vs. B (HR=4.38, p=0.011), and elevated AFP levels (HR=5.02, p<0.001). Positive responders saw substantial survival benefits (HR=0.26, p=0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p=0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment., Conclusion: Conversion therapy with curative intent following HAIC or ICIs might enhances survival in patients with advanced or TACE-unsuitable intermediate-stage HCC., (S. Karger AG, Basel.)

Background: The supraspinatus is most frequently involved in rotator cuff tears, a common orthopaedic condition. However, the architecture of this muscle has been described only for the superficial, anterior, and posterior regions., Purpose: To determine the muscle architecture of the deep supraspinatus., Study Design: Descriptive laboratory study., Methods: Muscle architecture measurements were collected from 25 cadaveric supraspinatus specimens (13 intact [without tendon tears], 3 with partial-thickness tears, 9 with full-thickness tears). The muscle was divided into deep, superficial anterior, and superficial posterior regions. Pennation angle, raw and normalized fiber length, and sarcomere length and number were compared using repeated-measures analyses of variance., Results: First, mean architecture measurements were compared between regions using only the intact specimens (n = 13). The deep region had a lower mean pennation angle (3.3° ± 1.0°) compared with the posterior region (11.0° ± 3.9°; P < .0001), which in turn had a significantly higher pennation angle compared with the anterior region (7.6 ± 2.6°; P = .0005). Normalized fiber lengths in the deep region were 21.1% ( P = .0052) and 34.5% ( P < .0001) shorter than the posterior and anterior normalized fiber lengths, respectively. Sarcomere lengths in the deep region were longer (3.4 ± 0.2 μm) compared with the posterior (3.1 ± 0.2 μm; P = .0012) and anterior (3.2 ± 0.2 μm; P = .0390) regions. Sarcomere numbers also decreased in the deep region by 21.2% ( P = .0056) and 34.2% ( P < .0001) compared with the posterior and anterior regions, respectively., Conclusion: The deep supraspinatus had significantly lower pennation angles, shorter fiber lengths, and fewer but longer sarcomeres in series compared with other subregions within the muscle. These structural differences suggest a functionally unique "submuscle" within the supraspinatus., Clinical Relevance: Understanding the architecture of the supraspinatus muscle can provide insight into muscle function in health and disease. Specifically, this deep submuscle may play a different role in rotator cuff function than the rest of the muscle., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Financial support was received from the Wu Tsai Human Performance Alliance and the Joe and Clara Tsai Foundation. J.G.L. has received education payments from ImpactOrtho and SportsTek Medical, consulting fees from Vericel, nonconsulting fees from Vericel, investment payments from Anika Therapeutics, honoraria from Vericel, and hospitality payments from Medtronic. A.S. has received education payments from Arthrex, ImpactOrtho, and SportsTek Medical; consulting fees from Arthrex; and nonconsulting fees from Arthrex and ImpactOrtho. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

The major limitation of cancer treatment is multidrug resistance (MDR), which leads to the inactivation of chemotherapeutic drugs and greater than 90% mortality. To solve this ordeal, we applied ligand-based drug design and bioiosteric replacement strategy from an indazole to a pyrazole ring to discover compounds 27 and 43 with good potential for reversing drug resistance in combination with paclitaxel, and their reversal fold values were 53.2 and 51.0 at 5 μM, respectively, against an MDR cancer cell line (KBvin). Based on the PK profile results, we selected compound 43 with a longer half-life for mechanistic and animal experiments. Combination treatment with compound 43 and paclitaxel-induced apoptosis and enhanced subG1 by decreasing mitochondrial membrane potential in KBvin cells. In addition, 43 also inhibited P-gp function by interfering with ATPase activity. Meanwhile, cotreatment with compound 43 and paclitaxel significantly suppressed tumor growth (TGI = 55.5%) at a dose of 200 mg/kg (PO) in a xenograft model and showed no obvious liver or kidney toxicity by H&E staining. Overall, compound 43 may serve as a safe and effective oral resistance reversal chemotherapeutic agent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Multidrug resistance (MDR) remains the most difficult problem facing conventional chemotherapy for cancers. Astragalus membranaceus is a historically traditional Chinese medicine. One of its bioactive components, formononetin, exhibits antitumor effects on various cancers. However, the effects of formononetin on MDR cancers have not been evaluated. Therefore, we investigated the defense's effects of formononetin on MDR. We used rhodamine 123 and doxorubicin efflux assays to analyze the inhibition kinetics of P-glycoprotein (P-gp) mediated-efflux. Cell viability was detected by sulforhodamine B assay, and the synergistic effects of formononetin combined with chemotherapeutic agents were further calculated using CompuSyn software. Molecular docking was performed with iGEMDOCK. We discovered that formononetin considerably induced oxidative stress and the disruption of mitochondrial membrane potential in MDR cancer cells. Furthermore, formononetin inhibits the P-gp efflux function by ATPase stimulation and the uncompetitive inhibition of P-gp-mediated effluxes of rhodamine 123 and doxorubicin. The molecular docking model indicates that formononetin may bind to P-gp by strong hydrogen bonds at Arginine (Arg) 489 and Glutamine (Gln) 912. Formononetin exhibits significant synergistic effects with vincristine and doxorubicin toward MDR cancer cells, and it synergistically suppressed tumor growth in vivo with paclitaxel. These results suggest that formononetin should be seen as a potential candidate for the adjuvant therapy of MDR cancers.

Background: High-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes., Methods: A retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173)., Results: Five patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071). The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%)., Conclusions: Esomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed., Competing Interests: Declaration of competing interest All authors declared there was no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Calcium silicate (CaSi) bone cement with antibacterial and osteogenic properties has attracted significant interest. However, there is a need to develop a variety of new premixed bone cement to meet the clinical requirements of fast setting time, ease of handling, and efficient antibacterial properties. In this study, different volume ratios of polyethylene glycol (PEG) and lactic acid liquids were added to calcium silicate, and the effects of varying liquid-to-powder ratios (L/P) were examined. This study assessed the physicochemical properties, cytotoxicity, and antibacterial activity against S. aureus and E. coli of this premixed cement. The results from the experiments indicated that lactic acid significantly reduced the setting time of the CaSi-based cement and enhanced its mechanical strength. Furthermore, the appropriate concentration of lactic acid and matching L/P ratio improved its washout resistance. The cell viability of all premixed cement was found to be over 80%. The premixed cement containing PEG and lactic acid exhibited superior antibacterial properties compared to the CaSi control. Based on its setting time, washout resistance, and antibacterial activity, a premixed cement with a liquid phase of 80% PEG and 20% lactic acid at an L/P ratio of 0.4 appeared promising for use in dental and orthopedic practice.

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, and it is mainly treated through lifestyle modifications. The very low-carbohydrate diet (VLCD) can help lose weight rapidly but the possible effects of extreme dietary patterns on lipid metabolism and inflammatory responses in individuals with NAFLD remain debatable. Moreover, VLCD protein content may affect its effectiveness in weight loss, steatosis, and inflammatory responses. Therefore, we investigated the effects of VLCDs with different protein contents in NAFLD rats and the mechanisms underlying these effects. After a 16-week inducing period, the rats received an isocaloric normal diet (NC group) or a VLCD with high or low protein content (NVLH vs. NVLL group, energy ratio:protein/carbohydrate/lipid=20/1/79 vs. 6/1/93) for the next 8 weeks experimental period. We noted that the body weight decreased in both the NVLH and NVLL groups; nevertheless, the NVLH group demonstrated improvements in ketosis. The NVLL group led to hepatic lipid accumulation, possibly by increasing very-low-density lipoprotein receptor (VLDLR) expression and elevating liver oxidative stress, subsequently activating the expression of Nrf2, and inflammation through the TLR4/TRIF/NLRP3 and TLR4/MyD88/NF-κB pathway. The NVLH was noted to prevent the changes in VLDLR and the TLR4-inflammasome pathway partially. The VLCD also reduced the diversity of gut microbiota and changed their composition. In conclusion, although low-protein VLCD consumption reduces BW, it may also lead to metabolic disorders and changes in microbiota composition; nevertheless, a VLCD with high protein content may partially alleviate these limitations., Competing Interests: Declaration of competing interest No author has any other financial conflicts of interest, and all authors adhered to the Committee on Publication Ethics guidelines on research and publication ethics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To effectively treat aggressive breast cancer by tumor-activated targetable photothermal chemotherapy, in this work, folate (FA)-modified hybrid polymeric nanoassemblies (HPNs) with a poly(ethylene glycol) (PEG)-detachable capability are developed as vehicles for tumor-targeted co-delivery of IR780, a lipophilic photothermal reagent, and zoledronic acid (ZA), a hydrophilic chemotherapy drug. Through hydrophobic interaction-induced co-assembly, IR780 molecules and ZA/poly(ethylenimine) (PEI) complexes were co-encapsulated into a poly(lactic- co -glycolic acid) (PLGA)-rich core stabilized by the amphiphilic FA-modified D-α-tocopheryl poly(ethylene glycol) succinate (FA-TPGS) and acidity-sensitive PEG-benzoic imine-octadecane (C18) (PEG- b -C18) conjugates. The developed FA-ZA/IR780@HPNs with high ZA and IR780 payloads not only showed excellent colloidal stability in a serum-containing milieu, but also promoted IR780-based photostability and photothermal conversion efficiency. Furthermore, for FA-ZA/IR780@HPNs under simulated physiological conditions, the premature leakage of IR780 and ZA molecules was remarkably declined. In a mimetic acidic tumor microenvironment, the uptake of FA-ZA/IR780@HPNs by FA receptor-overexpressed 4T1 breast cancer cells was remarkably promoted by PEG detachment combined with FA receptor-mediated endocytosis, thus effectively hindering migration of cancer cells and augmenting the anticancer efficacy of photothermal chemotherapy. Notably, the in vivo studies demonstrated that the FA-ZA/IR780@HPNs largely deposited at 4T1 tumor sites and profoundly suppressed tumor growth and metastasis without severe systemic toxicity upon near infrared (NIR)-triggered IR780-mediated hyperthermia integrated with ZA chemotherapy. This work presents a practical strategy to treat aggressive breast tumors with tumor-triggered targetable photothermal chemotherapy using FA-ZA/IR780@HPNs.

Background: Oncogenic multidrug resistance (MDR) is a tough question in cancer therapy. However, no effective medications targeting oncogenic MDR are currently available. Studies have demonstrated that mosloflavone exerts anti-inflammatory effects, yet, its potential to ameliorate MDR remains unclear., Purpose: This study aimed to access the capability and elucidate molecular mechanisms of mosloflavone as a MDR resensitizing candidate., Methods: We investigated the ability of mosloflavone to reverse oncogenic MDR and investigated its underlying mechanisms through cytotoxicity assay, cell cycle assay, apoptosis assay, and zebrafish xenograft model. The modulatory interplay between mosloflavone and P-gp was investigated through analysis of calcein-AM uptake, substrate efflux, ATPase assays, and molecular docking simulation., Results: Mosloflavone inhibited P-gp efflux function in an uncompetitive manner without altering ABCB1 gene expression. In addition, it stimulated P-gp ATPase activity by binding to an active site distinct from that of verapamil. Regarding MDR reversal potential, mosloflavone resensitized MDR cancer cells to chemotherapies by arresting cell cycle and triggering apoptosis, possibly by enhancing reactive oxygen species accumulation and reducing phospho-STAT3. Moreover, in the zebrafish xenograft model, mosloflavone significantly potentiated the antitumor effect of paclitaxel., Conclusion: Our findings underscore the potential of mosloflavone as a novel dual modulator of STAT3 and P-gp, indicating it is a promising candidate for overcoming MDR in cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Hybrid therapy is a recommended first-line anti- H. pylori treatment option in the American College of Gastroenterology guidelines, the Bangkok Consensus Report on H. pylori management, and the Taiwan H. pylori Consensus Report. However, the cure rates of eradication therapy in some countries are suboptimal, and the factors affecting the treatment efficacy of hybrid therapy remain unclear. The aim of this study is to identify the independent risk factors predicting eradication failure of hybrid therapy in the first-line treatment of H. pylori infection. A retrospective cohort study was conducted on 589 H. pylori -infected patients who received 14-day hybrid therapy between September 2008 and December 2021 in ten hospitals in Taiwan. The patients received a hybrid therapy containing a dual regimen with a proton pump inhibitor (PPI) plus amoxicillin for an initial 7 days and a quadruple regimen with a PPI plus amoxicillin, metronidazole and clarithromycin for a final 7 days. Post-treatment H. pylori status was assessed at least 4 weeks after completion of treatment. The relationships between eradication rate and 13 host and bacterial factors were investigated via univariate and multivariate analyses. In total, 589 patients infected with H. pylori infection were included in the study. The eradication rates of hybrid therapy were determined as 93.0% (95% confidence interval (CI): 90.9-95.1%), 94.4% (95% CI: 93.8-97.2%) and 95.5%% (95% CI: 93.8-97.2%) by intention-to-treat, modified intention-to-treat and per-protocol analyses, respectively. Univariate analysis showed that the eradication rate of clarithromycin-resistant strains was lower than that of clarithromcyin-susceptible strains (83.3% (45/54) vs. 97.6%% (280/287); p < 0.001). Subjects with poor drug adherence had a lower cure rate than those with good adherence (73.3% (11/15) vs. 95.5% (534/559); p = 0.005). Other factors such as smoking, alcohol drinking, coffee consumption, tea consumption and type of PPI were not significantly associated with cure rate. Multivariate analysis revealed that clarithromcyin resistance of H. pylori and poor drug adherence were independent risk factors related to eradication failure of hybrid therapy with odds ratios of 4.8 (95% CI: 1.5 to 16.1; p = 0.009) and 8.2 (95% CI: 1.5 to 43.5; p = 0.013), respectively. A 14-day hybrid therapy has a high eradication rate for H. pylori infection in Taiwan, while clarithromycin resistance of H. pylori and poor drug adherence are independent risk factors predicting eradication failure of hybrid therapy.

Multidrug resistance (MDR) is considered one of the significant chemotherapy failures of cancer patients and resulting in tumor recurrence and refractory cancer. The collateral sensitivity phenomenon is suggested as a potential alternative therapy for coring multidrug resistance in cancer. To achieve better effects and reduce toxicity, a polypharmacology strategy was applied. Arctigenin has been reported as a signal transducer and activator of transcription 3 (STAT3) inhibitor as an anticancer drug with low toxicity. However, the effective dosage of arctigenin was too high for re-sensitization in MDR cell lines. Therefore, we have designed and synthesized arctigenin derivatives and have evaluated their chemoreversal effects in KBvin and KB cells. The results conveyed that compounds 9, 10, and 12 displayed significant collateral sensitivity effects on MDR cancer cells, and the corresponding calculated RF values were 32, 174, and 133, respectively. In addition, compounds 9, 10, and 12 were identified to influence the activation of STAT3 and the function of P-glycoprotein in KBvin cells. Combining the active compounds (9, 10, and 12) with paclitaxel significantly inhibits MDR tumor growth in a zebrafish xenograft tumor model without toxicity. Thus, this study provided novel effective arctigenin derivatives and is considered a potential co-treatment with paclitaxel for treating MDR tumors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hsin-Yi Hung and Chin-Chuan Hung reports financial support was provided by Ministry of science of technology., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Helicobacter pylori (H. pylori) infection is the principal cause of chronic gastritis, gastric ulcers, duodenal ulcers, and gastric cancer. In clinical practice, diagnosis of H. pylori infection by a gastroenterologists' impression of endoscopic images is inaccurate and cannot be used for the management of gastrointestinal diseases. The aim of this study was to develop an artificial intelligence classification system for the diagnosis of H. pylori infection by pre-processing endoscopic images and machine learning methods. Endoscopic images of the gastric body and antrum from 302 patients receiving endoscopy with confirmation of H. pylori status by a rapid urease test at An Nan Hospital were obtained for the derivation and validation of an artificial intelligence classification system. The H. pylori status was interpreted as positive or negative by Convolutional Neural Network (CNN) and Concurrent Spatial and Channel Squeeze and Excitation (scSE) network, combined with different classification models for deep learning of gastric images. The comprehensive assessment for H. pylori status by scSE-CatBoost classification models for both body and antrum images from same patients achieved an accuracy of 0.90, sensitivity of 1.00, specificity of 0.81, positive predictive value of 0.82, negative predicted value of 1.00, and area under the curve of 0.88. The data suggest that an artificial intelligence classification model using scSE-CatBoost deep learning for gastric endoscopic images can distinguish H. pylori status with good performance and is useful for the survey or diagnosis of H. pylori infection in clinical practice., (© 2023. Springer Nature Limited.)

Introduction: Rotator cuff tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration, which is not improved upon with surgical repair, highlighting the need to better understand the underlying biology impairing more favorable outcomes. Methods: In this study, we collected supraspinatus muscle tissue from 6 month old female rabbits who had undergone unilateral tenotomy for 8 weeks at 1, 2, 4, or 8 weeks post-repair ( n = 4/group). RNA sequencing and enrichment analyses were performed to identify a transcriptional timeline of rotator cuff muscle adaptations and related morphological sequelae. Results: There were differentially expressed (DE) genes at 1 (819 up/210 down), 2 (776/120), and 4 (63/27) weeks post-repair, with none at 8 week post-repair. Of the time points with DE genes, there were 1092 unique DE genes and 442 shared genes, highlighting that there are changing processes in the muscle at each time point. Broadly, 1-week post-repair differentially expressed genes were significantly enriched in pathways of metabolism and energetic activity, binding, and regulation. Many were also significantly enriched at 2 weeks, with the addition of NIF/NF-kappaB signaling, transcription in response to hypoxia, and mRNA stability alongside many additional pathways. There was also a shift in transcriptional activity at 4 weeks post-repair with significantly enriched pathways for lipids, hormones, apoptosis, and cytokine activity, despite an overall decrease in the number of differentially expressed genes. At 8 weeks post-repair there were no DE genes when compared to control. These transcriptional profiles were correlated with the histological findings of increased fat, degeneration, and fibrosis. Specifically, correlated gene sets were enriched for fatty acid metabolism, TGF-B-related, and other pathways. Discussion: This study identifies the timeline of transcriptional changes in muscle after RC repair, which by itself, does not induce a growth/regenerative response as desired. Instead, it is predominately related to metabolism/energetics changes at 1 week post-repair, unclear or asynchronous transcriptional diversity at 2 weeks post-repair, increased adipogenesis at 4 weeks post-repair, and a low transcriptional steady state or a dysregulated stress response at 8 weeks post-repair., Competing Interests: Author AS was employed by Kaiser Permanente. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Vasquez-Bolanos, Gibbons, Ruoss, Wu, Esparza, Fithian, Lane, Singh, Nasamran, Fisch and Ward.)

Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells.

Background and Aim: Most consensuses recommend culture-guided therapy as third-line Helicobacter pylori treatment. This study aimed to investigate the efficacies of culture-guided therapy and empirical therapy with high-dose proton pump inhibitor (PPI) in the H. pylori third-line treatment., Methods: Between August 2012 and October 2021, H. pylori-infected patients with at least two failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose rabeprazole and/or bismuth. They were categorized into three groups: patients who had positive results of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth quadruple therapy, patients who had positive results of culture with one or two susceptible antibiotics were treated by culture-guided bismuth-containing therapy, and patients who had a negative result of culture were treated by an empirical therapy with high-dose rabeprazole plus amoxicillin, tetracycline and levofloxacin. A post-treatment assessment was conducted at week 8., Results: We recruited 126 patients. The eradication rates of culture-guided non-bismuth quadruple therapy (n = 50), culture-guided bismuth-containing therapy (n = 46) and empirical therapy (n = 30) were 84.0%, 87.0%, and 66.7% (95% confidence interval: 73.8-94.2%, 77.3-96.7%, and 49.8-83.6%), respectively. Overall, culture-guided therapy achieved a higher eradication rate than empirical therapy (85.4% vs 66.7%; 95% confidence interval, 0.4% to 37.0%, P = 0.022)., Conclusions: Culture-guided therapy with high-dose PPI achieves a higher eradication rate than empirical therapy with high-dose PPI in the third-line treatment of H. pylori infection. The eradication rate of rescue therapy with bismuth plus two susceptible antibiotics is not inferior to that with three susceptible antibiotics., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Diagnosis and treatment of posterior shoulder instability (PSI) has improved with advances in imaging and surgical technique. However, the relationship between PSI and osteoarthritis (OA) remains unclear., Purpose: To evaluate a population-based cohort to (1) determine the rate of symptomatic OA, (2) identify patient characteristic risk factors for OA, and (3) evaluate the effect of posterior capsulolabral repair on OA progression., Study Design: Case-control study; Level of evidence, 3., Methods: After review of 324 patient records, we included 115 patients (14 female, 101 male) diagnosed with PSI between January 1994 and July 2012 with an average follow-up of 12.5 years (range, 5-23 years). Medical records were reviewed for patient characteristics, injury characteristics, surgical details (if any), and radiographic progression of OA. Kaplan-Meier survival was used to estimate survival free of OA; characteristics associated with OA progression were determined via univariate Cox regression models, and associated 95% CIs and hazard ratios (HRs) are presented., Results: Overall, 14% (16/115) of patients had radiographic progression of symptomatic glenohumeral arthritis, with 5-year survival of 88.3% (95% CI, 79.7%-97.3%). Older age at the time of instability diagnosis was associated with arthritis progression (10-year unit HR, 1.95; 95% CI, 1.26-3.03). Patients who underwent surgery demonstrated increased radiographic progression of OA (HR, 4.03; 95% CI, 1.23-13.23). There was a trend of increased OA in patients treated with labral debridement compared with repair despite lower baseline levels of OA; however, this difference was not statistically significant ( P = .09)., Conclusion: Symptomatic glenohumeral arthritis is not seen routinely in patients with PSI. Although uncommon, an age of at least 30 years at the time of diagnosis and surgical intervention were identified as risk factors for developing symptomatic arthritis at long-term follow-up., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: The authors acknowledge support from the Foderaro-Quattrone Musculoskeletal-Orthopaedic Surgery Research Innovation Fund. This study was partially funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases for the Musculoskeletal Research Training Program (T32AR56950). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. J.L. has received support for education from Peerless Surgical and Sequoia Surgical; speaking fees from Arthrex; and hospitality payments from Biomet, Encore Medical, and Wright Medical. A.J.K. has received research support from Aesculap/B. Braun, Arthritis Foundation, Ceterix, Exactech, Gemini Medical, and Histogenics; consulting fees from Arthrex, DePuy, JRF Ortho, Musculoskeletal Transplant Foundation (MTF), and Vericel; and speaking fees from Arthrex and MTF and is a board or committee member for MTF. D.L.D. has received research support from Arthrex and hospitality payments from GE Healthcare and is a board or committee member for the NBA/GE Strategic Advisory Board. Her spouse receives royalties from and owns stock/stock options in Sonex Health and Tenex Health. C.L.C. has received education payments from Arthrex and hospitality payments from Arthrex and Zimmer Biomet. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Calcium silicate-based cement (CSC) has attracted much interest because of its favourable osteogenic effect that supports its clinical use. Although CSC has antibacterial activity, this activity still needs to be improved when used in an infected bone defect. Natural polyphenols have been considered antimicrobial reagents. To this end, three different types of polyphenols (gallic acid (GA), pyrogallol (PG) and tannic acid (TA)) with different concentrations as a liquid phase were mixed with bioactive calcium silicate to enhance the antibacterial activity of CSC. The setting time, antibacterial activity, and osteogenic activity of CSC were studied. Evaluation of antibacterial ability and reactive oxygen species (ROS) was performed using Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus aureus ( S. aureus ) bacteria, while a human osteoblast-like cell line (MG63) was used to examine osteogenic activity. The experimental results showed that the addition of polyphenols did not remarkably affect the phase composition and morphology of CSC, but changed the setting time and diametral tensile strength. At the same concentration of 1 wt%, the setting time of TA (21 min) was significantly shorter than that of PG (26 min) and GA (68 min), and was indistinguishable from the control cement (20 min). GA had a significantly higher antioxidant activity than PG and TA. As expected, higher concentrations of polyphenols had a more positive impact on ROS generation. More importantly, the incorporation of polyphenols greatly enhanced the antibacterial activity of CSC against E. coli and S. aureus , but had little effect on the in vitro osteogenic activity of MG63 cells and the cytotoxicity of L929 cells. It was concluded that among the three phenolic compounds, the optimal concentration of the liquid phase in the hybrid cement was 5 wt% TA in terms of setting time, strength, antibacterial activity and in vitro osteogenic activity.

Rotator cuff (RC) tears present a treatment challenge due to muscle atrophy and degeneration, fatty infiltration, and fibrosis. The purpose of this study was to generate a high time-resolution model of RC tear in rabbits and to characterize the progression of architectural and histological changes. Thirty-five female New Zealand White rabbits (age: 6 months) underwent left supraspinatus tenotomy. Five rabbits were used to evaluate immediate muscle architectural changes. The remaining 30 rabbits underwent right shoulder sham surgery and sacrifice at 1, 2, 4, 8, or 16 weeks. Histology was used to quantify muscle fiber cross-sectional area (CSA), muscle degeneration and regeneration, and fat localized to inter- versus intrafascicular regions. Muscle fiber CSA decreased by 26.5% compared to sham at 16 weeks (effect of treatment, p < 0.0001). Muscle degeneration increased after tenotomy (effect of treatment, p = 0.0006) without any change in regeneration. Collagen and fat content increased by 4 weeks and persisted through 16 weeks. Interfascicular fat was increased at all time points, but intrafascicular fat was increased only at 1, 4, and 16 weeks posttenotomy. Intrafascicular fat adjacent to degenerating muscle fibers increased as well (effect of treatment, p < 0.0001; effect of time, p = 0.0102). Statement of clinical relevance: Rabbit supraspinatus tenotomy recapitulates key features of the pathophysiology of human RC tears, including muscle atrophy and degeneration, lack of regeneration, fat accumulation, and fibrosis., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background and Objectives: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. People who inject drugs (PWIDs) constitute the majority of patients with HCV infection in the United States and Central Asia. There are several obstacles to treating HCV infection in PWIDs because PWIDs are often accompanied by concurrent infection, low compliance, substance abuse, and risky behavior. The aim of the study is to compare the efficacies of direct-acting antiviral (DAA) therapy for HCV infection in PWIDs and those without opioid injection. Materials and Methods: In this retrospective cohort study, we included 53 PWIDs with HCV infections treated on site in a methadone program and 106 age- and sex-matched patients with HCV infections who had no history of opioid injection (ratio of 1:2). All eligible subjects received anti-HCV treatment by DAA agents in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAA agents, and treatment outcomes. The primary outcome measure was sustained virological response (SVR). Results: PWIDs and non-drug users had different HCV genotype profiles (p = 0.013). The former had higher proportions of genotype 3 (18.9% vs. 7.5%) and genotype 6 (24.5% vs. 14.2%) than the latter. The two patient groups had comparable rates of complete drug refilling (100.0% vs. 91.1%) and frequency of loss to follow-up (3.8% vs. 0.9%). However, PWIDs had a lower SVR rate of DAA treatment than non-drug users (92.2% vs. 99.0%; p = 0.04). Further analysis showed that both human immunodeficiency virus (HIV) coinfection and history of PWID were risk factors associated with treatment failure. The subjects with coinfection with HIV had lower SVR rates than those without HIV infection (50.0% vs. 96.5%; p = 0.021). Conclusions: PWIDs with HCV infections have higher proportions of HCV genotype 3 and genotype 6 than non-drug users with infections. DAA therapy can achieve a high cure rate (>90%) for HCV infection in PWID, but its efficacy in PWID is lower than that in non-drug users.

The rabbit supraspinatus is a useful translational model for rotator cuff (RC) repair because it recapitulates muscle atrophy and fat accumulation observed in humans after a chronic tear (the "first hit"). However, a timeline of RC tissue response after repair, especially with regard to recent evidence of muscle degeneration and lack of regeneration, is currently unavailable. Thus, the purpose of this study was to characterize the progression of muscle and fat changes over time after the repair of a chronic RC tear in the rabbit model. Two rounds of experiments were conducted in 2017-2018 and 2019-2020 with N = 18 and 16 skeletally mature New Zealand White rabbits, respectively. Animals underwent left supraspinatus tenotomy with repair 8 weeks later. The unoperated right shoulder served as control. The rabbits were sacrificed at 1-, 2-, 4-, and 8-weeks post-repair for histological and biochemical analysis. Atrophy, measured by fiber cross-sectional area and muscle mass, was greatest around 2 weeks after repair. Active muscle degeneration peaked at the same time, involving 8% of slide areas. There was no significant regeneration at any timepoint. Fat accumulation and fibrosis were significantly increased across all time points compared to contralateral. Statement of Clinical Significance: These results demonstrate model reproducibility and a "second hit" phenomenon of repair-induced muscle atrophy and degeneration which partially recovers after a short time, while increased fat and fibrosis persist., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wu, Gibbons, Esparza, Vasquez-Bolanos, Hyman, Dorn, Singh, Lane, Fithian, Ruoss and Ward.)

Cancer multi-drug resistance (MDR) caused by P-glycoprotein (P-gp) efflux is a critical unresolved clinical concern. The present study analyzed the effect of cinnamophilin on P-gp inhibition and MDR reversion. The effect of cinnamophilin on P-gp was investigated through drug efflux assay, ATPase assay, MDR1 shift assay, and molecular docking. The cancer MDR-reversing ability and mechanisms were analyzed through cytotoxicity and combination index (CI), cell cycle, and apoptosis experiments. P-gp efflux function was significantly inhibited by cinnamophilin without influencing the drug's expression or conformation. Cinnamophilin uncompetitively inhibited the efflux of doxorubicin and rhodamine 123 and exhibited a distinct binding behavior compared with verapamil, the P-gp standard inhibitor. The half maximal inhibitory concentration of cinnamophilin for doxorubicin and rhodamine 123 efflux was 12.47 and 11.59 μM, respectively. In regard to P-gp energy consumption, verapamil-stimulated ATPase activity was further enhanced by cinnamophilin at concentrations of 0.1, 1, 10, and 20 μM. In terms of MDR reversion, cinnamophilin demonstrated synergistic cytotoxic effects when combined with docetaxel, vincristine, or paclitaxel. The CI was < 0.7 in all experimental combination treatments. The present study showed that cinnamophilin possesses P-gp-modulating effects and cancer MDR resensitizing ability., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Chronic rotator cuff tears can cause severe functional deficits. Addressing the chronic fatty and fibrotic muscle changes is of high clinical interest; however, the architectural and physiological consequences of chronic tear and repair are poorly characterized. We present a detailed architectural and physiological analysis of chronic tear and repair (both over 8 and 16 wk) compared with age-matched control rabbit supraspinatus (SSP) muscles. Using female New Zealand White Rabbits ( n = 30, n = 6/group) under 2% isoflurane anesthesia, the SSP was surgically isolated and maximum isometric force was measured at four to six muscle lengths. Architectural analysis was performed, and maximum isometric stress was computed. Whole muscle length-tension curves were generated using architectural measurements to compare experimental physiology to theoretical predictions. Architectural measures are consistent with persistent radial and longitudinal atrophy over time in tenotomy that fails to recover after repair. Maximum isometric force was significantly decreased after 16 wk tenotomy and not significantly improved after repair. Peak isometric force reported here are greater than prior reports of rabbit SSP force after tenotomy. Peak stress was not significantly different between groups and consistent with prior literature of SSP stress. Muscle strain during contraction was significantly decreased after 8 wk of tenotomy and repair, indicating effects of tear and repair on muscle function. The experimental length-tension data were overlaid with predicted curves for each experimental group (generated from structural data), exposing the altered structure-function relationship for tenotomy and repair over time. Data presented here contribute to understanding the physiological implications of disease and repair in the rotator cuff. NEW & NOTEWORTHY We utilize an established method to measure the length-tension relationship for the rabbit supraspinatus in normal, torn, and repaired muscles. We then perform architectural analysis to evaluate structural changes after tear and repair. Although peak isometric force is lower in the tear and repair groups, there are no differences in peak stresses across groups. These findings indicate persistent structural changes (both radial and longitudinal atrophy) and physiological deficiencies (decreased peak force and uncoupling structure-function relationship) after tenotomy that do not significantly recover after repair.

Background/purpose: Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population., Methods: The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions., Results: The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population., Conclusion: The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Background: The Maastricht V/Florence Consensus Report recommends amoxicillin-fluoroquinolone triple or quadruple therapy as a second-line treatment for Helicobacter pylori infection. An important caveat of amoxicillin-fluoroquinolone rescue therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. The study aimed to investigate the efficacies of tetracycline-levofloxacin (TL) quadruple therapy and amoxicillin-levofloxacin (AL) quadruple therapy in the second-line treatment of H. pylori infection., Methods: Consecutive H. pylori-infected subjects after the failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (tetracycline 500 mg QID, levofloxacin 500 mg QD, esomeprazole 40 mg BID, and tripotassium dicitrato bismuthate 300 mg QID) or AL quadruple therapy (amoxicillin 500 mg QID, levofloxacin 500 mg QD, esomeprazole 40 mg BID, and tripotassium dicitrato bismuthate 300 mg QID) for 10 days. Post-treatment H. pylori status was assessed 6 weeks after the end of therapy., Results: The study was early terminated after an interim analysis. In the TL quadruple group, 50 out of 56 patients (89.3%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved only in 39 of 52 patients (69.6%) receiving AL quadruple therapy. Intention-to-treat analysis showed that TL quadruple therapy achieved a markedly higher eradication rate than AL quadruple therapy (95% confidence interval: 4.8% to 34.6%; p = 0.010). Further analysis revealed that TL quadruple therapy had a high eradication rate for both levofloxacin-susceptible and resistant strains (100% and 88.9%). In contrast, AL quadruple therapy yielded a high eradication for levofloxacin-susceptible strains (90.9%) but a poor eradication efficacy for levofloxacin-resistant strains (50.0%). The two therapies exhibited comparable frequencies of adverse events (37.5% vs 21.4%) and drug adherence (98.2% vs 94.6%)., Conclusions: Ten-day TL quadruple therapy is more effective than AL quadruple therapy in the second-line treatment of H. pylori infection in a population with high levofloxacin resistance., (© 2021 John Wiley & Sons Ltd.)

Multidrug resistance (MDR), for which the mechanisms are not yet fully clear, is one of the major obstacles to cancer treatment. In recent years, signal transducer and activator of transcription 3 (STAT3) were found to be one of the important MDR mechanism pathways. Based on the previous research, zhankuic acid A, B, and C were found to have collateral sensitivity effects on MDR cancer cells, and MDR inhibitory activity of zhankuic acid methyl ester was found to be better than that of its acid. Therefore, we executed a systematic examination of the structure-activity relationship of zhankuic acid methyl ester derivatives to collateral sensitivity in MDR cancer cells. The results showed that compound 12 is the best in terms of chemoreversal activity, where the reversal fold was 692, and the IC 50 value of paclitaxel combined with 10 μM compound 12 treatment was 1.69 nM in MDR KBvin cells. Among all the derivatives, methyl ester compounds were found to be better than their acids, and a detailed discussion of the structure-activity relationships of all of the derivatives is provided in this work. In addition, compounds 8 , 12, and 26 were shown to influence the activation of STAT3 in KBvin cells, accounting for part of their chemoreversal effects. Our results may provide a new combined therapy with paclitaxel to treat multidrug-resistant cancers and provide a new therapy option for patients.

Rotator cuff (RC) tears are prevalent in the population above the age of 60. The disease progression leads to muscle atrophy, fibrosis, and fatty infiltration in the chronic state, which is not improved with intervention or surgical repair. This highlights the need to better understand the underlying dysfunction in muscle after RC tendon tear. Contemporary studies aimed at understanding muscle pathobiology after RC tear have considered transcriptional data in mice, rats and sheep models at 2-3 time points (1 to 16 weeks post injury). However, none of these studies observed a transition or resurgence of gene expression after the initial acute time points. In this study, we collected rabbit supraspinatus muscle tissue with high temporal resolution (1, 2, 4, 8, and 16 weeks) post-tenotomy ( n = 6/group), to determine if unique, time-dependent transcriptional changes occur. RNA sequencing and analyses were performed to identify a transcriptional timeline of RC muscle changes and related morphological sequelae. At 1-week post-tenotomy, the greatest number of differentially expressed genes was observed (1,069 up/873 down) which decreases through 2 (170/133), 4 (86/41), and 8 weeks (16/18), followed by a resurgence and transition of expression at 16 weeks (1,421/293), a behavior which previously has not been captured or reported. Broadly, 1-week post-tenotomy is an acute time point with expected immune system responses, catabolism, and changes in energy metabolism, which continues into 2 weeks with less intensity and greater contribution from mitochondrial effects. Expression shifts at 4 weeks post-tenotomy to fatty acid oxidation, lipolysis, and general upregulation of adipogenesis related genes. The effects of previous weeks' transcriptional dysfunction present themselves at 8 weeks post-tenotomy with enriched DNA damage binding, aggresome activity, extracellular matrix-receptor changes, and significant expression of genes known to induce apoptosis. At 16 weeks post-tenotomy, there is a range of enriched pathways including extracellular matrix constituent binding, mitophagy, neuronal activity, immune response, and more, highlighting the chaotic nature of this time point and possibility of a chronic classification. Transcriptional activity correlated significantly with histological changes and were enriched for biologically relevant pathways such as lipid metabolism. These data provide platform for understanding the biological mechanisms of chronic muscle degeneration after RC tears., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vasquez-Bolanos, Gibbons, Ruoss, Wu, Vargas-Vila, Hyman, Esparza, Fithian, Lane, Singh, Nasamran, Fisch and Ward.)

Purpose: To compare rates of recurrent instability, revision surgery and functional outcomes following arthroscopic anterior capsulolabral repair for recurrent anterior instability using knot-tying versus knotless suture anchor techniques., Methods:  Patients who had undergone arthroscopic anterior labrum and capsular repair for recurrent anterior glenohumeral instability using knotless anchors were identified. Those with minimum 2-year follow-up were matched (1:2) to knot-tying anchor repair patients. Rates of failure and recurrent instability were compared, as well as Visual Analog Scale (VAS), Single Assessment Numeric Evaluation (SANE), Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), University of California Los Angeles (UCLA) and Rowe scores., Results: One hundred and two patients (89 males, 13 females) with a mean age of 24.3 ± 9.6 were included. Repair was performed with knotless anchors in 34 and knot-tying anchors in 68 shoulders. At mean follow-up of 4.8 ± 2.5 years, re-dislocation rates between groups were not significantly different (knotless anchor: 9% versus knot-tying group: 15%, n.s.), but the knot-tying group showed a higher re-subluxation rate (p = 0.039). 12 (18%) revisions were performed in the knot-tying group at a mean 2.9 years after surgery and 1 (3%) revision in the knotless anchors group at 1.4 years (n.s.). There was no difference in mean VAS with use (1.3 ± 1.9 versus 0.8 ± 1.5, n.s.), SANE scores (91.8 ± 12.7 versus 92.0 ± 11.0, n.s.), QuickDASH scores (4.1 ± 5.5 versus 3.0 ± 6.5, n.s.), UCLA Shoulder Score (32.5 ± 3.6 versus 33.2 ± 3.1, n.s.), or Rowe scores (90.5 ± 18.5 versus 92.2 ± 16.6, n.s.) between knotless and knot-tying groups, respectively. VAS at rest was higher in the knotless group (0.7 ± 1.5 vs 0.1 ± 0.4, p = 0.021)., Conclusions: Knotless anchors demonstrated similar rates of re-dislocation and revision surgery, and lower rates of recurrent subluxation, compared to knot-tying anchors. Patients achieved good-to-excellent functional outcomes. This supports the efficacy of knotless anchors as an alternative to knot-tying anchors for arthroscopic anterior labral repair of recurrent anterior shoulder dislocation., Level of Evidence: III.

The purpose of this study was to evaluate the physicochemical properties and the in vitro and in vivo osteogenesis of the newly developed calcium silicate containing 5 wt% gelatin (CSG) cement compared with calcium silicate (CS) and calcium sulfate hemihydrate (CSH) cements. In addition to the phase composition and microstructure, washout resistance, setting time, and diametral tensile strength of the bone cements were also performed. In vitro examination of cell growth, differentiation, and mineralization were performed with macrophage cell line (RAW 264.7), MG63 human osteoblast-like cells, and human mesenchymal stem cells (hMSCs). The mini-pig model with mandibular alveolar bone defect was used to assess the in vivo function of cement. Histological and histomorphometric assessments were performed at 6 and 12 weeks after implantation. The results indicated that the CS and CSG powders were mainly composed of poorly crystalline β-dicalcium silicate, and the irregular CSH powders had a highly crystalline phase. After setting, the product of CS and CSG was calcium-silicate-hydrate gel and CSH exhibited a plate-like gypsum crystal structure. The setting time of CS, CSG, and CSH was 19, 35, and 10 min, respectively. Gelatin effectively improved the washout resistance and diametral tensile strength of CS from 2.4 MPa to 3.4 MPa, while CSH had no washout resistance and its strength was 7.6 MPa. The osteogenic activity of MG63 and hMSC cells on the CSG cement surface was consistently shown to be significantly higher than that on the CSH cement surface. Interestingly, CS and CSG cements exhibited lower macrophage expression compared to CSH cements. Twelve week after implantation, the amount of new bone in the defect area of the CS group was slightly higher than that of the CSG and CSH groups. It is concluded that CSG cement had improved anti-washout performance, favorable osteogenesis in vitro and in vivo, which was beneficial for clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD)., Methods: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort., Results: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years)., Conclusion: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.

There is limited evidence guiding management of medial collateral ligament (MCL) avulsions or functional disruptions distal to the medial joint line. This study aims to determine outcomes of a series of patients with grade III distal MCL injuries managed with acute surgical repair. Patients with grade III, distal MCL injuries, with or without multiligament involvement were identified. Demographic, clinical examination, and midterm patient-reported outcomes (PRO) data were collected. Clinical follow-up included physical examination and ligamentous stress testing at a minimum of 6 months. PROs included Lysholm's knee scoring scale, Tegner's activity score, and subjective International Knee Documentation Committee (IKDC) scores at minimum of 2 years follow-up. Of the 24 eligible patients, outcomes data were available for 20 (83%). Of the 20 included patients, 16 had a concomitant anterior cruciate ligament (ACL) injury, 3 had ACL and posterior cruciate ligament (PCL) injuries, and 1 had an isolated MCL injury. Mean time from injury to surgery was 5 weeks. At mean clinical follow-up of 20.3 months, all patients showed valgus stability and satisfactory range of motion (ROM). Anteroposterior stability was normal in all but one patient who demonstrated a 2+ posterior drawer but with firm end points. At a mean follow-up of 5.7 years for PROs, mean Lysholm's score was 91.5 (standard deviation [SD] = 12.2), median Tegner's activity score was 7 (range, 4-9), and mean subjective IKDC score was 88.8 (SD: 9.9). The surgical repair of grade III distal MCL injuries delivered satisfactory clinical and functional outcomes. Future comparative studies with larger patient samples are needed., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Calcium silicate (CaSi) materials have been used for bone repair and generation due to their osteogenic properties. Tailoring the surface chemistry and structure of CaSi can enhance its clinical performance. There is no direct comparison between microscale and nanoscale CaSi particles. Therefore, this article aimed to compare and evaluate the surface chemistry, structure, and in vitro properties of microscale CaSi (μCaSi) and nanoscale CaSi (nCaSi) particles synthesized by the sol-gel method and precipitation method, respectively. As a result, the semi-crystalline μCaSi powders were assemblies of irregular microparticles containing a major β-dicalcium silicate phase, while the amorphous nCaSi powders consisted of spherical particles with a size of 100 nm. After soaking in a Tris-HCl solution, the amount of Si ions released from nCaSi was higher than that released from μCaSi, but there was no significant difference in Ca ion release between the two CaSi particles. Compared to microscale CaSi (μCaSi), nanoscale CaSi (nCaSi) significantly enhanced the growth and differentiation of human mesenchymal stem cells (hMSC) and inhibited the function of RAW 264.7 macrophages. In the case of antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), nanoscale nCaSi displayed a higher bacteriostatic ratio, a greater growth inhibition zone and more reactive oxygen species (ROS) production than microscale μCaSi. The conclusion is that nanoscale CaSi had greater antibacterial and osteogenic activity compared to microscale CaSi. Next generation CaSi-based materials with unique properties are emerging to meet specific clinical needs.

Bone marrow edema (BME) can be a late finding in osteoarthritis or a sign of subchondral insufficiency. The purpose of this study was to describe the magnetic resonance imaging (MRI) finding we refer to as "osteomeniscal impact edema" (OMIE), or reactive BME adjacent to a displaced meniscus flap tear. In addition, this edema pattern is compared with a control group of medial meniscus posterior root tears (MMPRT) with subchondral insufficiency edema. MRI records from 2000 to 2017 were retrospectively reviewed for studies that showed the presence of a medial meniscus displaced flap tear and an adjacent area of BME. The selected MRIs were matched to an equal number of MMPRT MRI studies. All MRI studies were assessed for cartilage surface grade using the modified Outerbridge classification system and for the extent of accompanying structural abnormalities using the whole-organ magnetic resonance imaging score. Descriptive statistics and hypothesis testing were utilized to compare the MRI findings between groups. Twenty-two flap tear (OMIE group) patients with a mean age of 57 (SD: 15) and 22 root tear (MMPRT) group patients with a mean age of 61 (SD: 10) were included. MRIs in the OMIE group showed a distinctive pattern of focal, peripheral edema adjacent to the meniscus flap tear, compared with more diffuse, central edema in the MMPRT group. Quantitatively, MRIs of the MMPRT group showed significantly worse mean femoral Outerbridge scores (3.72 vs. 2.68, p  < 0.0001), more severe central (1.63 vs. 0.5, p  = 0.0007) and posterior (0.31 vs. 0.0, p  = 0.04) subchondral edema grades, and a higher incidence of tibial subchondral fractures (3 vs. 0, p  = 0.036). Meniscus flap tears may present with a distinct MRI pattern of focal, adjacent, peripheral edema, which we refer to as OMIE. Patients with meniscus flap tears showed significantly less arthritic change, lower subchondral edema grades, and a lower incidence of insufficiency fractures and subchondral collapse compared with the diffuse overload edema pattern found with root tears. The Level of Evidence for this study is III., Competing Interests: M. J. S. reports other from American Journal of Sports Medicine; grants, personal fees, non-financial support and other from Arthrex, Inc.; and grants from Styrker, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Calcium silicate cement has attracted much attention for bone defect repair and regeneration due to its osteogenic properties. Biomaterial-associated infections and washout have become a common clinical problem. In order to enhance the antibacterial and washout performance of calcium silicate cement to meet clinical needs, different types of chitosan, including chitosan polysaccharide (CTS), quaternary ammonium chitosan (QTS), and chitosan oligosaccharide (COS), as a liquid phase were added to the calcium silicate powder. The physicochemical properties, in vitro bioactivity, antibacterial efficacy, and osteogenic effects (MG63 cells) of the cement were evaluated. Antibacterial activity was conducted with Gram-negative Escherichia coli (E. coli) and a Gram-positive Staphylococcus aureus (S. aureus) bacteria. The amount of intracellular reactive oxygen species (ROS) produced in the bacteria cultured with the chitosan solution was also detected. The experimental results showed that the chitosan additive did not affect the crystalline phase of calcium silicate cement, but increased the setting time and strength of the cement in a concentration-dependent manner. Within the scope of this study, CTS and QTS solutions with a concentration of not <1 wt% improved the washout resistance of the control cement, while the COS solutions failed to strengthen the cement. When soaked in simulated body fluid (SBF) for 1 day, all cement samples formed apatite spherules. As the soaking time increased, the diametral tensile strength of all cements decreased and the porosity increased. The assays of MG63 cell function showed lower osteogenic activity of osteoblastic cells grown on the surfaces of the chitosan-incorporated cements in comparison with the control cement without chitosan. At the same 1% concentration, compared with QTS and COS cement, CTS cement had lower cell attachment, proliferation, differentiation, and mineralization. Conversely, the CTS cement resulted in the highest bacteriostasis ratio among the three hybrid cements against two bacteria. The ROS production followed the order of CTS > QTS > COS at the same 1% concentration. In conclusion, calcium silicate cement with 1% QTS may be a viable candidate for bone defect repair in view of anti-washout performance, setting time, antibacterial activity, and osteogenic activity shown in this study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To (1) define the rate of delayed surgery, between 1 and 10 years after injury, in a population-based study of patients with posterior shoulder instability (PSI), (2) evaluate predictive factors associated with delayed repair, and (3) identify differences between the nonoperative and operative groups at long-term follow-up., Methods: A population-based retrospectively reviewed study of all patients with PSI from January 1, 1994, to December 31, 2015, was performed. Inclusion required a clinical diagnosis of PSI combined with supporting imaging. Complete medical records were reviewed for 2,091 potential cases. Kaplan-Meier estimates were used to calculate survival. Landmark survival analysis was performed to identify predictors of conversion to surgery., Results: The study included 143 patients with PSI, 79 of whom were managed nonoperatively for at least 1 year after diagnosis. After the first year, survival free of surgery was 78.3% at 1 year, 63.1% at 5 years, and 51.5% at 10 years. There was a trend toward increased surgery in patients with a body mass index > 35 (P = .10; hazard ratio = 2.32; confidence interval, 0.8-6.8). Nonthrowing athletes (including contact/weight-lifting athletes) showed a trend toward an increased risk for surgery (P = .07). Patients who underwent surgery were significantly more likely to have progression in arthritis (P = .02; hazard ratio = 4.0; confidence interval, 1.2-13.2)., Conclusions: Nonoperative management was performed for at least 1 year in over half of patients diagnosed with PSI. Overall, long-term follow-up demonstrates that 46% of these patients converted to surgery between 1 and 10 years after initial diagnosis. Ultimately, 70% of patients diagnosed with PSI go on to surgical intervention. Patients who underwent surgery at any time point were at an increased risk of radiographic progression of arthritis at a minimum of 5 years of follow-up., Level of Evidence: Level III, cohort study., (Copyright © 2019 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background/purpose: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease affecting oral health. Evidence shows possible association between T1DM and periodontal diseases (PDs). We conducted a nationwide population-based study in Taiwan, with a 14-year follow-up to investigate the risk of PDs in T1DM patients., Methods: We used data from the National Health Insurance Research Database in Taiwan. The T1DM cohort was identified with newly diagnosed T1DM from 1998 to 2011. The non-T1DM cohort was frequency matched with the T1DM cohort. Participants comprised 4248 patients in the T1DM cohort and 16992 persons in the non-T1DM cohort., Results: The T1DM patients showed an increased risk of PDs compared to non-T1DM individuals [adjusted hazard ratio (aHR) = 1.45]. T1DM patients who visited the emergency room more than twice per year had a higher aHR of 13.0 for developing PDs. The aHR for PDs was 13.2 in the T1DM patients who had been hospitalized more than twice per year., Conclusion: T1DM patients are at higher risk of developing PDs than non-T1DM individuals. Our results further showed that the number of T1DM interventions; that is, annual emergency visits and hospitalizations were associated with increased the risk of developing PDs., (Copyright © 2018. Published by Elsevier B.V.)

Background: The incidence of posterior shoulder instability (PSI) in the general population is not well defined. This study aimed to define the population-based incidence of PSI and describe trends in incidence and surgery rates., Methods: The study population included 143 patients (16 females, 127 males) diagnosed with new-onset PSI between January 1, 1994, and December 31, 2015. Medical records were reviewed to extract patient data. Age- and sex-specific incidence rates were calculated and adjusted to the 2010 United States population. Poisson regression was performed to examine trends by timeline, sex, and age., Results: Age- and sex- adjusted annual incidence of PSI was 4.64 per 100,000 person-years, and posterior dislocation was 1.30 per 100,000 person-years. Peak PSI incidence for males and females was at 14 to 19 years (31.82 and 5.23 per 100,000 person-years). PSI incidence was higher in males than females (8.86 vs. 1.07 per 100,000 person-years, P < .001). The 5-year cumulative risk of surgery for patients with PSI was 53.1% between 1996 and 2002, 59.9% between 2003 and 2008, and 87.5% between 2009 and 2015. Patients with PSI between 2009 and 2015 had a significantly increased rate of surgery (hazard ratio, 2.2; 95% confidence interval, 1.4-3.6; P = .001) compared with those between 1996 and 2002., Conclusion: The age- and sex- adjusted incidence of PSI in the general population was 4.64 per 100,000 person-years. There is a significantly greater incidence of PSI in males than females, with both sexes peaking at 14 to 19 years and incidence rates remaining elevated throughout the third and fourth decades of life. The incidence of PSI remained stable over time; however, the rate of surgical intervention increased significantly, from 53.1% of patients between 1996 and 2002 to 87.5% of patients between 2009 and 2015., (Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Purpose: Various implant materials have been used in medial, opening-wedge high tibial osteotomy (HTO) including traditional metal and modern polyetheretherketone (PEEK) implants. The purpose of this study was to compare metal and PEEK implants and determine safety, varus deformity correction, as well as short- to mid-term hardware removal and arthroplasty rates., Methods: HTO performed with metal and PEEK implants were reviewed between 2000 and 2015 at two institutions with a minimum of 2 years follow-up. Postoperative complications, radiographic measures, and osteotomy union were compared between groups using Kruskal-Wallis and Fisher's exact testing. Survival free of hardware removal and arthroplasty was compared between groups using Kaplan-Meier testing. Risk factors for HTO conversion to arthroplasty were examined using Cox proportional hazards regression., Results: Ninety-five HTOs were performed in 90 patients (59 M, 31 F) using 50 metal and 45 PEEK implants. Mean follow-up was 4.2 years (range 2.0-16.5). Two metal and two PEEK HTO patients experienced nonunions, resulting in revision HTO at a mean of 1.0 years postoperatively (range 0.4-1.4 years). Both implant groups demonstrated similar, significant improvements in coronal deformity, with mean angulation improving from 6.0° and 5.4° varus preoperatively to 1.1° and 1.0° valgus postoperatively for the metal (p < 0.01) and PEEK groups (p < 0.01), respectively. 2- and 5-year hardware removal-free survival was 94% and 94% for PEEK, which was significantly superior to 80% and 73% observed for metal (p = 0.02). 2- and 5-year arthroplasty-free survival was similar for the metal (98% and 94%) and PEEK groups (100% and 78%) (n.s.). HTO performed for focal cartilage defects was observed to demonstrate decreased arthroplasty risk (HR 0.36, p = 0.03) when compared to HTO performed for osteoarthritis., Conclusions: Both metal and PEEK implants were found to be effective in obtaining and maintaining coronal varus deformity correction, with 88% overall arthroplasty-free survival at 5 years. Metal fixation demonstrated a higher rate of hardware removal while HTO performed for medial compartment osteoarthritis predicted conversation to arthroplasty., Level of Evidence: III.

Background: Surgical reconstruction of the anterior cruciate ligament (ACL) is one of the most common orthopaedic procedures, with an estimated 100,000 to 175,000 procedures performed annually. Recently, the all-inside reconstruction technique has come into favor and is theorized to be superior to the complete tibial tunnel technique., Purpose: To compare clinical and patient-reported outcomes (PROs) for hamstring autograft ACL reconstruction (ACLR) performed with an all-inside versus a complete tibial tunnel technique., Study Design: Cohort study; Level of evidence, 3., Methods: Patients who underwent hamstring autograft ACLR via either an all-inside approach (femoral and tibial sockets) or a complete tibial tunnel approach (femoral socket and full-length, transtibial tunnel) at a single institution between July 2011 and July 2015 were reviewed. Demographic information, preoperative comorbidities, surgical details, physical examination findings, and follow-up outcomes were extracted from the medical record. Physical examination data included pivot-shift, Lachman, and range of motion examinations, whereas PROs included the Tegner activity scale, Lysholm score, and International Knee Documentation Committee (IKDC) score at a minimum of 2 years after surgery. Return to sport and risk factors for failure were analyzed., Results: A total of 82 patients (mean ± SD age, 25.8 ± 10.2 years) who underwent all-inside reconstruction (median PRO follow-up, 30.1 months; range, 24.7-72.9 months) and 54 patients (mean ± SD age, 21.1 ± 7.3 years) who underwent complete tibial tunnel reconstruction (median PRO follow-up, 25.8 months; range, 23.9-74.5 months) met the inclusion criteria. PRO scores at latest follow-up were comparable between the all-inside versus the complete tibial tunnel groups (Lysholm score, 93.8 vs 94.4, P = .621; IKDC score, 93.5 vs 93.3, P = .497; Tegner activity score, 6.4 vs 6.8, P = .048). Complications (including graft failure) were experienced by 20% of patients in the all-inside group compared with 24% in the complete tibial tunnel group ( P = .530). Graft failure before the final follow-up was experienced by 10% of patients in the all-inside group compared with 19% in the complete tibial tunnel group ( P = .200). Mean return to sport was 12.5 months in the all-inside group versus 9.9 months in the complete tibial tunnel group ( P = .028)., Conclusion: All-inside and complete tibial tunnel hamstring autograft ACLR resulted in excellent physical examination findings and PROs at minimum 2-year follow-up. Both techniques successfully restored knee stability and patient function., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: B.A.L. receives royalties from Arthrex; is a paid consultant for Arthrex and Smith & Nephew; and receives research support from Arthrex, Biomet, Smith & Nephew, and Stryker. D.L.D. receives research support from Arthrex and is a member of the NBA/GE Strategic Advisory Board, and her spouse has stock/stock options in and receives royalties from Tenex Health and Sonex Health. C.L.C. has received educational support from Arthrex and Zimmer Biomet and hospitality payments from Arthrex. A.J.K. receives research support from Aesculap/B. Braun and the Arthritis Foundation; receives royalties from Arthrex; and is a paid consultant for Arthrex, Vericel, DePuy Orthopaedics, and the Musculoskeletal Transplant Foundation. M.J.S. receives royalties from Arthrex, is a paid consultant for Arthrex, receives research support from Stryker, and has received hospitality payments from Gemini Medical. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Objective: Distal femoral varus osteotomy (DFVO) is an effective treatment for unloading valgus knee malalignment; however, there is limited evidence on the ability for patients to return to athletics following this procedure. The purpose of this study is to report the functional outcomes and rate of return to sport for athletes that underwent DFVO., Design: A consecutive series of athletes that had undergone DFVO were retrospectively reviewed. Radiographs were assessed to determine preoperative and postoperative alignment. Institutional registries were used to collect preoperative and postoperative Marx Activity Scale, International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form scores, and return to sport., Results: Thirteen patients (8 males, 5 females) with a mean age of 24 years (range 17-35 years) and a mean follow-up of 43 months (range 24-74 months) were included in the study. Six patients underwent medial closing wedge DFVO versus 7 patients who underwent lateral opening wedge DFVO. Nine of 13 had concomitant chondral, meniscal, or ligamentous procedures performed. The mean alignment correction was 8° (range 5°-13°). All patients were able to successfully return to sport at a mean of 11 months (range 9-13 months). Furthermore, all 13 patients demonstrated an improvement in both Marx Activity Scale (4-11; P < 0.01) and IKDC scores (53-89; P < 0.01) after surgery., Conclusions: Correction of valgus knee malalignment through DFVO-either medial closing wedge or lateral opening wedge-can reliably result in improvement in function and return to sport. Concomitant chondral, meniscal, and ligamentous pathology should be addressed.

Injury to the posterolateral corner (PLC) of the knee can lead to both varus and rotational instability. Multiple PLC reconstruction techniques have been described, including one-tailed graft (fibula-based constructs) or two-tailed graft (combined fibula- and tibia-based constructs). The purpose of our study was to evaluate the clinical outcomes of anatomical two-tailed graft reconstruction of the PLC in the setting of multiligament knee injuries (MKLIs) with grade III varus instability. Patients were identified through a prospective MLKI database between 2004 and 2013. Patients who received fibular collateral ligament and PLC reconstructions using a two-tailed graft and had a minimum follow-up of 2 years were included. Patients were assessed for clinical laxity grade, range of motion, and functional outcomes using Lysholm and International Knee Documentation Committee (IKDC) scores. Twenty patients (16 male, 4 female) with a mean age of 30.7 (range: 16-52) and a mean follow-up of 52.2 months (range: 24-93 months) were included. Knee dislocation (KD) grades included: 4 KD-1, 10 KD 3-L, 5 KD-4, and 1 KD-5. No patients had isolated PLC injuries. Mean IKDC and Lysholm score were 73.1 ± 25.8 and 78 ± 26, respectively. Mean range of motion was -1.1 to 122.8. In full extension, two patients (10%) had grade 1 laxity to varus stress. In 30 degrees of knee flexion, five (25%) patients had grade 1 laxity, and two (10%) had grade 2 laxity. Anatomical two-tailed PLC reconstruction can reliably restore varus stability when performed on patients with MLKIs and type C posterolateral instability with hyperextension external rotation recurvatum deformity. Satisfactory functional outcome scores were achieved in the majority of patients. This study supports the use of an anatomical two-tailed PLC reconstruction in the multiligament injured knee. The level of evidence is IV, case series., Competing Interests: Michael J. Stuart: American Journal of Sports Medicine: Editorial or governing board; Arthrex, Inc: IP royalties, paid consultant; Stryker: Research support. Bruce A. Levy: Arthrex, Inc: IP royalties, paid consultant, research support; Arthroscopy, Journal of Arthroscopic and Related Research, Journal of Knee Surgery, Knee Surgery, Sports Traumatology: Editorial or governing board; Biomet: Research support; CORR: Editorial or governing board; Smith & Nephew: Paid consultant, Research support; Stryker: Research support. Aaron J. Krych: Aesculap/B.Braun: Research support; American Journal of Sports Medicine: Editorial or governing board; Arthrex, Inc: IP royalties, paid consultant; Arthritis Foundation: Research support; Ceterix: Research support; Histogenics: Research support; International Cartilage Repair Society: Board or committee member; International Society of Arthroscopy, Knee Surgery, and Orthopaedic Sports Medicine: Board or committee member; Minnesota Orthopedic Society: Board or committee member; Musculoskeletal Transplantation Foundation: Board or committee member; Vericel: Paid consultant., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: The preoperative assessment of cartilage lesions is critical to surgical planning and decision making. The accurate radiographic determination of acetabular cartilage damage has remained elusive for modern imaging modalities, including magnetic resonance imaging (MRI) and magnetic resonance arthrography (MRA). While risk factors have been individually described, no multivariable system exists for predicting high-grade cartilage damage., Purpose: To determine the preoperative predictors of grade 3 to 4 acetabular labrum articular disruption (ALAD) lesions., Study Design: Case-control study; Level of evidence, 3. Cohort study (diagnosis); Level of evidence, 1., Methods: Retrievable radiographs were reviewed from primary hip arthroscopic procedures performed at 2 high-volume institutions between December 2007 and April 2017. The predictive value of demographic and radiographic factors for the intraoperative documentation of ALAD grade 3 to 4 damage was analyzed and entered into a multivariable model, and a statistically guided scoring system for the damage risk was created using the Akaike information criterion. The scoring system was then prospectively validated on 167 patients who underwent primary hip arthroscopy between April 2017 and February 2018., Results: A total of 652 primary hip arthroscopic procedures in 614 patients (390 female, 224 male; mean age, 33.2 ± 12.5 years; mean body mass index, 26.9 ± 5.5 kg/m 2 ) from 2007 to 2017 were analyzed. Male sex (odds ratio [OR], 3.11; P < .01), age ≥35 years (OR, 1.96; P < .01), cam morphology (alpha angle >55°) (OR, 2.96; P < .01), and Tönnis grade 1 to 2 (grade 1: OR, 4.14; P < .01, and grade 2: OR, 9.29; P < .01) were univariate risk factors for intraoperatively documented high-grade damage. A multivariable scoring system, the Rapidly Assessed Predictor of Intraoperative Damage (RAPID) score (0-5 points), was generated based on sex, Tönnis grade, and cam morphology. Patients with increasing RAPID scores had an increasing risk of damage, with a 10.5% risk for those with 0 points and an 88.0% risk for those with 5 points ( P < .01). The area under the curve was 0.75 for the study group and 0.76 for the validation group ( P = .94)., Conclusion: While preoperative MRI has diagnostic value for hip arthroscopic surgery, the RAPID score provides added benefit as a readily employable, in-clinic system for predicting high-grade cartilage damage. The discriminatory value of the RAPID score compares favorably with previous MRI and MRA studies. This information will help the clinician and patient plan for high-grade damage and identify potential targets for cartilage treatment., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.H. has received hospitality payments from DePuy. D.E.H. has received educational support from Arthrex and Smith & Nephew and hospitality payments from Desert Mountain Medical and Stryker. D.B.F.S. is a paid speaker/presenter for Smith & Nephew and is a paid consultant for Smith & Nephew, Genzyme, and TiGenix. B.A.L. receives royalties from Arthrex and VOT Systems, is a paid consultant for Arthrex, and is a paid speaker/presenter for the Canadian Orthopaedic Association and Smith & Nephew. A.J.K. receives research support from Aesculap/B. Braun, the Arthritis Foundation, Ceterix, and Histogenics; receives royalties from Arthrex; is a paid consultant for Arthrex, Vericel, and DePuy; and has received honoraria from Vericel and the Musculoskeletal Transplant Foundation. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: An initial episode of patellar instability poses a treatment challenge given the absence of a valid, reproducible, and universally applicable predictor of recurrence. Recently, a series of patellar instability ratios (PIRs) were described. Each ratio consisted of the traditional tibial tubercle to trochlear groove (TT-TG) distance normalized to patient-specific measures. The purpose of this study was to investigate the reliability and validity of these novel measures., Methods: Eighty-seven patients experiencing a first-time lateral patellar dislocation were identified in a retrospective manner. Magnetic resonance imaging (MRI) studies obtained at the time of injury were reviewed. The TT-TG distance, patellar width (PW), trochlear width (TW), patellar length (PL), and trochlear length (TL) were obtained by two observers in a blinded, randomized fashion. Measurement reliability was assessed using intra-class correlation coefficients (ICCs). Patients were divided into those having a single dislocation (Group 1) and those experiencing recurrent instability (Group 2). The ability of the TT-TG distance and each PIR to predict recurrent instability was assessed by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity and specificity were also calculated for each measure., Results: Excellent inter-rater agreement was observed with ICCs > 0.75 for all patellofemoral joint measurements obtained on MRI. The TT-TG distance alone was predictive of recurrent patellar instability with an OR of 8.9 (p < 0.001). However, the isolated TT-TG distance had the lowest sensitivity at 25.6%. Among ratios, a TT-TG/PL ≥ 0.5 was the most predictive of recurrent instability with an ORs of 6.1 (p = < 0.001). A TT-TG/TL ≥ 0.8 was also predictive of recurrence (OR 4.9, p = 0.027) and had the highest sensitivity of any measure at 94.9%., Conclusion: The results of the current study support the reproducibility and predictive ability of PIRs. While a TT-TG ≥ 20 mm was the strongest predictor of recurrent patellar instability, it was a relatively insensitive measure. Sensitivity may be improved by normalizing the TT-TG distance to patient-specific axial and sagittal plane patellofemoral measurements on MRI. Ultimately, PIRs are reproducible measures that may serve as an additional tool when clinically assessing the unstable patellofemoral joint., Level of Evidence: III.

Background: Full-thickness radial meniscal tears render the meniscus nonfunctional and have historically been treated with partial meniscectomy. As preservative techniques evolve for radial repair, comparisons with other tear patterns are necessary to evaluate repair efficacy and prognosis., Purpose: To assess clinical outcomes and reoperation rates of radial meniscal repair and to compare them to bucket-handle meniscal repair., Study Design: Cohort study; Level of evidence, 3., Methods: Radial and bucket-handle meniscal tears without concurrent root injuries undergoing surgical repair at a single institution between 2007 and 2015 were analyzed, including both all-inside and inside-out suturing techniques. Propensity matching was performed on the basis of age at surgery, sex, meniscus laterality, body mass index (BMI), and concomitant anterior cruciate ligament reconstruction (ACLR) using a comparison pool of 70 bucket-handle repairs. Reoperation-free survival rates and Tegner, visual analog scale (VAS) for pain, and International Knee Documentation Committee (IKDC) scores were analyzed., Results: Twenty-four patients (18 male, 6 female; mean age, 22.8 ± 11.9 years) who underwent repair of a radial meniscal tear were followed for a mean of 3.5 years (range, 2.0-6.3 years). Significant postoperative improvements in VAS scores at rest and with use and IKDC scores were noted postoperatively ( P < .001). Five patients (20.8%) required a reoperation. Subsequently, 18 patients with radial tears (mean age, 19.1 ± 9.1 years; 12 male; mean BMI, 27.0 ± 6.2 kg/m 2 ; 3 medial; 11 ACLR) were propensity matched to 18 patients with bucket-handle tears (mean age, 20.8 ± 5.1 years; 13 male; mean BMI, 25.0 ± 3.5 kg/m 2 ; 3 medial; 11 ACLR). The matched radial and bucket-handle groups demonstrated similar ( P = .17) reoperation-free survival rates at 2 years (88.9% and 94.4%, respectively) and 5 years (77.8% and 87.7%, respectively). VAS and IKDC scores improved significantly after surgery ( P < .001), with no difference noted between the groups ( P ≥ .17). Patients with radial and bucket-handle meniscal repairs achieved mean postoperative Tegner scores (6.6 and 6.6, respectively) not significantly different from their preinjury levels (6.9 and 6.7, respectively) ( P ≥ .32)., Conclusion: Satisfactory clinical outcomes are achievable for radial meniscal tear repair at short-term follow-up. In a robustly matched comparison, radial and bucket-handle meniscal tears demonstrate similar improvements in VAS and IKDC scores, restoration of preoperative Tegner scores, and acceptable reoperation rates. Full-thickness radial meniscal tears should be considered for repair.

Purpose: To determine the cyclic displacement and ultimate failure loads of two clinically relevant suture configurations for repair of medial and lateral meniscus root tears., Methods: A total of 10 matched pair fresh-frozen, human meniscus specimens were randomly assigned to either simple cinch or locking loop meniscus-suture fixation techniques for transtibial pull-out repair in either medial (n = 10 matched pairs) or lateral (n = 10 matched pairs) meniscal root tears. The menisci were subjected to cyclic tensioning at 10-30 N for 1000 cycles at 0.5 Hz, and then post-cycling load to failure was performed at a tensile rate of 0.5 mm/s., Results: For both the medial and lateral meniscus, there was significantly less displacement with the cinch stitch at 100, 500 and 1000 cycle counts (p < 0.05). In respect to ultimate load, there was no significant difference in type of repair between the two suture configurations. When comparing ultimate load to failure from the medial to the lateral side, the ultimate load to failure was significantly greater for both suture configurations in the lateral meniscus root repair (p < 0.05). However, there was no significant difference in cyclic displacement between the medial and lateral meniscus., Conclusions: The cinch stitch was significantly better at resisting displacement compared to the locking loop stitch configuration, and had similar ultimate load to failure. The lateral meniscus root repair construct has higher failure loads compared to the medial meniscus, independent of suture configuration.

Background: Osteochondritis dissecans (OCD) is a disorder of unknown origin that can affect knees in skeletally mature and immature patients. Surgical management is an important cornerstone of treatment for unstable OCD lesions., Purpose: To determine the (1) healing rate after internal fixation of unstable OCD between skeletally immature and mature knees, (2) risk factors for failure, and (3) patient-reported outcomes among healed patients., Study Design: Cohort study; Level of evidence, 3., Methods: A multicenter retrospective cohort study was conducted with patients who underwent internal fixation of unstable knee OCD lesions from 2000 to 2015. Skeletal immaturity was defined as open or partially open physes. Healing was assessed through clinical findings and imaging. Definitive reoperation for the same OCD lesion was classified as failure., Results: Among 87 patients included, 66 (76%) had healed lesions at ≥2 years postoperatively, while 21 (24%) failed. Skeletal maturity made no significant difference in failure rate (risk ratio, 0.68; 95% CI, 0.29-1.72; P = .40). For skeletally immature patients, lateral versus medial condylar location conferred an increased hazard of 18.2 (95% CI, 1.76-188.07; P < .01). Multivariate analysis factoring in skeletal maturity showed that lateral condylar location was an independent risk factor for failure (hazard ratio, 4.25; 95% CI, 1.47-19.85; P < .01). Mean patient-reported outcome scores (International Knee Documentation Committee [IKDC] and Knee injury and Osteoarthritis Outcome Score [KOOS]) increased significantly after surgery, except the KOOS symptoms score for the skeletally mature group. Final scores (mean ± SD) were as follows at a mean follow-up of 60 months (range, 24-166): IKDC, 83.5 ± 20.2; KOOS pain, 89.7 ± 14.1; KOOS symptoms, 87.4 ± 18.4; KOOS activities of daily living, 93.9 ± 12.7; KOOS sports, 80.7 ± 25.9; KOOS quality of life, 78.9 ± 23.1., Conclusion: Skeletally immature and mature patients heal at comparable rates after internal fixation of OCD lesions, resulting in functional and subjective improvement. Lateral femoral condylar lesion location is an independent risk factor for failure.

Background: Studies assessing dysplasia's effect on hip arthroscopy are often limited to the short term and unable to account for demographic factors that may vary between dysplastic and nondysplastic populations., Purpose: To determine the midterm failure rate and patient-reported outcomes of arthroscopic labral repair in the setting of dysplasia and make subsequent failure and outcome comparisons with a rigorously matched nondysplastic control group., Study Design: Cohort study; Level of evidence, 3., Methods: Primary arthroscopic labral repair cases at 2 centers from 2008 to 2011 were reviewed. Patients with lateral center edge angle (LCEA) <25° were matched to nondysplastic controls by age, sex, laterality, body mass index (BMI), Tönnis grade, and capsular repair per a 1:2 matching algorithm. Groups were compared with a visual analog scale (VAS) for pain, modified Harris Hip Score (mHHS), and Hip Outcome Score-Sports Specific Subscale (HOS-SSS) to determine predictors of outcome and failure., Results: Forty-eight patients with dysplasia (mean LCEA, 21.6°; range, 13.0°-24.9°; n = 25 with capsular repair) were matched to 96 controls (mean LCEA, 32.1°; range, 25°-52°; n = 50 with capsular repair) and followed for a mean of 5.7 years (range, 5.0-7.7 years). Patients achieved mean VAS improvements of 3.3 points, mHHS of 19.5, and HOS-SSS of 29.0 points ( P < .01) with no significant differences between the dysplasia and control populations ( P > .05). Five-year failure-free survival was 83.3% for patients with dysplasia and 78.1% for controls ( P = .53). No survival or outcomes difference was observed between patients with dysplasia who did or did not have capsular repair ( P ≥ .45) or when comparing LCEA <20° and LCEA 20° to 25° ( P ≥ .60). BMI ≤30 was associated with increased revision surgery risk ( P < .01). Age >35 years ( P < .05) and Tönnis grade 0 radiographs ( P < .01) predicted failure to reach minimal clinically important differences., Conclusion: With careful selection and modern techniques, patients with dysplasia can benefit significantly and durably from arthroscopic labral repair. The dysplastic cohort had outcomes and failure rates similar to those of rigorously matched controls at midterm follow-up. Subanalyses comparing LCEA <20° and LCEA 20° to 25° are presented for completeness; however, this study was not designed to detect differences in dysplastic subpopulations. BMI ≤30 was associated with increased revision risk. Age >35 years and Tönnis grade 0 radiographs predicted failure to achieve minimal clinically important differences.

Background: Lateral meniscus posterior root tears (LMPRTs), if left untreated, can cause devastating effects to the knee, with rapid articular cartilage degeneration and loss of the meniscus as a secondary stabilizer. Detection and surgical repair of these defects have been linked to favorable outcomes, but preoperative identification of LMPRTs continues to be challenging., Purpose: To determine the rate of LMPRTs diagnosed preoperatively on magnetic resonance imaging (MRI) in a consecutive series of arthroscopically confirmed LMPRTs., Study Design: Case series; Level of evidence, 4., Methods: A retrospective cohort of 45 consecutive patients with arthroscopically confirmed LMPRTs between 2010 and 2017 were included in this study. The preoperative MRI report for each patient was evaluated and compared with intraoperative findings. Each preoperative MRI study was then reviewed by 2 fellowship-trained musculoskeletal radiologists who worked in consensus., Results: A total of 45 patients (32 males, 13 females) with arthroscopically confirmed LMPRTs and a mean age of 27 years (range, 14-54 years) were included in the study. Only 15 of 45 LMPRTs (33%) were initially diagnosed on preoperative MRI. Past or concurrent anterior cruciate ligament (ACL) reconstruction was present in 37 of 45 cases (82%). Upon retrospective review, 15 of the 30 missed LMPRTs were "clearly evident," 12 "subtly evident," and 3 "occult" (unavoidably missed). There were no significant differences in the rate of LMPRT diagnosis based on history of prior knee surgery, meniscus extrusion, or tearing of the meniscofemoral ligament., Conclusion: Despite improved identification of other meniscus tear patterns on MRI, a high percentage of LMPRTs were still missed. In the setting of previous ACL reconstruction, if the root cannot be confidently identified, the MRI interpretation should indicate that "the root is poorly visualized" to alert the surgeon to thoroughly evaluate this structure. The surgeon should maintain a high index of suspicion and carefully probe the posterior root of the lateral meniscus at the time of arthroscopy, especially in cases of ACL injury., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: A.J.K. receives research support from Aesculap/B. Braun, the Arthritis Foundation, Ceterix, and Histogenics; is a paid consultant for Arthrex and Vericel; and is on the board of the Musculoskeletal Transplant Foundation. D.B.F.S. receives research support from Arthrex, Ivy Sports, and Smith & Nephew and is a paid consultant for Cartiheal, Smith & Nephew, and Vericel. B.A.L. receives royalties from Arthrex; is paid consultant for Arthrex and Smith & Nephew; and receives research support from Arthrex, Biomet, Smith & Nephew, and Stryker. M.J.S. is a paid consultant for Arthrex, receives royalties from Arthrex, and receives research support from Stryker.