The Impact of Bone Marrow Stimulation on Arthroscopic Rotator Cuff Repair for Small to Large Rotator Cuff Tears: A Randomized Controlled Trial.

BACKGROUND: Bone marrow stimulation (BMS), a procedure involving the creation of multiple channels in the greater tuberosity, is often performed alongside arthroscopic rotator cuff repair (ARCR). This study evaluated the effect of BMS on clinical and structural outcomes following ARCR. METHOD: This study involved 204 patients with small, medium, and large full-thickness rotator cuff tears. In all, 103 patients who underwent BMS and ARCR made up the BMS group, while the 101 patients who only had ARCR made up the control group with randomization. Clinical and functional outcomes were assessed before and at 3 months, 6 months, 1 year, and 2 years after surgery, using parameters such as range of motion, functional scores (ASES and constant score), and clinical scores (VAS). Tendon integrity was also examined postoperatively via ultrasound at 6 months and 2 years. RESULTS: There were no significant differences between the two groups concerning range of motion, functional scores (ASES score and constant score), and clinical score (VAS) during the 2-year post-surgery period (all p>0.05). Similarly, the rotator cuff retear rate, as assessed using ultrasonographic tendon integrity checks over 2 years post-surgery, did not significantly vary between the groups (all p>0.05). CONCLUSION: There were no significant disparities in functional scores and clinical outcomes between the BMS and control groups. Further, no significant differences were observed in tendon integrity post-surgery. Therefore, the inclusion or exclusion of BMS is not anticipated to influence the postoperative outcome in ARCR for patients with small, medium, or large rotator cuff tears.

Comparing domain- and intensity-specific physical activity in coronary heart disease and non-CHD individuals.

Although increase in physical activity is important to improve prognosis of cardiac patients in addition to hospital-based exercise cardiac rehabilitation, their physical activity levels are not properly understood. This study aimed to examine domain- and intensity-specific physical activity in individuals with coronary heart disease (CHD) and compare them with non-CHD individuals. Data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2014 to 2019 were analyzed, including 1083 CHD patients and 38,532 non-CHD individuals. The inclusion criteria were age 19 years or older and data not missing for CHD information. Before and after propensity score matching (PSM) for age, sex, body mass index, education, household income, alcohol intake, and smoking status, domain (leisure, work, transportation)-and intensity (moderate, vigorous) -specific physical activity participation levels were compared between individuals with and without CHD. Before PSM, CHD individuals were older, less educated, more sedentary, and participated less in PAs compared to non-CHD individuals. After PSM, CHD individuals had similar levels of domain-specific PAs. However, they had higher work-related PA levels (29.7 ± 209.6 vs. 42.1 ± 291.3 min/week p = 0.022) and more sedentary time (487.2 ± 224.2 vs. 514.1 ± 228.7. p = 0.003) than those without CHD. Subgroup analysis revealed lower leisure-related PA in men with CHD (63.5 ± 165.5 vs. 47.3 ± 140.2, p < 0.05) and higher work-related PA in women with CHD (18.9 ± 159.7 vs. 57.1 ± 397.5, p < 0.01). Among those < 65 years of age, individuals with CHD spent more time sedentary than individuals without CHD. CHD individuals are not physically inactive compared with non-CHD individuals who are similar in sociodemographic status and lifestyle. CHD patients' PA levels may have been underestimated.

Activation of transient receptor potential vanilloid 1 ameliorates tau accumulation-induced synaptic damage and cognitive dysfunction via autophagy enhancement.

AIMS: The autophagy-lysosomal pathway is important for maintaining cellular proteostasis, while dysfunction of this pathway has been suggested to drive the aberrant intraneuronal accumulation of tau protein, leading to synaptic damage and cognitive impairment. Previous studies have demonstrated that the activation of transient receptor potential vanilloid 1 (TRPV1) by capsaicin has a positive impact on cognition and AD-related biomarkers. However, the effect and mechanism of TPRV1 activation on neuronal tau homeostasis remain elusive. METHODS: A mouse model of tauopathy was established by overexpressing full-length human tau in the CA3 area. Mice were fed capsaicin diet (0.0125%) or normal diet for 9 weeks. The cognitive ability, synaptic function, tau phosphorylation levels, and autophagy markers were detected. In vitro, capsaicin-induced alterations in cellular autophagy and tau degradation were characterized using two cell models. Besides, various inhibitors were applied to validate the role of TRPV1-mediated autophagy enhancement in tau clearance. RESULTS: We observed that TRPV1 activation by capsaicin effectively mitigates hippocampal tau accumulation-induced synaptic damages, gliosis, and cognitive impairment in vivo. Capsaicin promotes the degradation of abnormally accumulated tau through enhancing autophagic function in neurons, which is dependent on TRPV1-mediated activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the mammalian target of rapamycin (mTOR). Blocking AMPK activation abolishes capsaicin-induced autophagy enhancement and tau degradation in neurons. CONCLUSION: Our findings reveal that capsaicin-induced TRPV1 activation confers neuroprotection by restoring neuronal tau homeostasis via modulating cellular autophagy and provides additional evidence to support the potential of TRPV1 as a therapeutic target for tauopathies.

Death-associated protein kinase 1 phosphorylates MDM2 and inhibits its protein stability and function.

Breast cancer is one of the major malignancies in women, and most related deaths are due to recurrence, drug resistance, and metastasis. The expression of the mouse double minute 2 (MDM2) oncogene is upregulated in breast cancer; however, its regulatory mechanism has yet to be fully elucidated. Herein, we identified the tumor suppressor death-associated protein kinase 1 (DAPK1) as a novel MDM2 regulator by unbiased peptide library screening. DAPK1 is directly bound to MDM2 and phosphorylates it at Thr419. DAPK1-mediated MDM2 phosphorylation promoted its protein degradation via the ubiquitin-proteasome pathway, resulting in upregulated p53 expression. DAPK1 overexpression, but not its kinase activity-deficient form, decreased colony formation and increased doxorubicin-induced cell death; however, DAPK1 knockdown produced the opposite effects in human breast cancer cells. In a xenograft tumorigenesis assay, DAPK1 overexpression significantly reduced tumor formation, whereas inhibition of DAPK1 kinase activity reduced its antitumorigenic effect. Finally, DAPK1 expression was negatively correlated with MDM2 levels in human breast cancer tissues. Thus, these results suggest that DAPK1-mediated MDM2 phosphorylation and its protein degradation may contribute to its antitumorigenic function in breast cancer.

Semen quality and sperm DNA fragmentation in cancer patients undergoing sperm cryopreservation.

PURPOSE: We compared semen quality and sperm DNA fragmentation in cancer patients who underwent sperm banking and controls who underwent sperm cryopreservation for assisted reproductive technology (ART). MATERIALS AND METHODS: A total of 132 men, 65 cancer patients and 67 controls, were prospectively enrolled and performed sperm cryopreservation for fertility preservation from May 2019 to February 2021. Sperm quality was determined by measuring semen volume, sperm concentration, sperm motility, and sperm DNA fragmentation index (DFI). Sperm quality and sperm DFI were compared in cancer patients and controls. RESULTS: The major cancers of the 65 cancer patients were leukemia (26.2%), testicular cancer (23.1%), and lymphoma (20.0%). Sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls. Sperm DFI was significantly higher in cancer patients than in controls (24.32%±15.69% vs. 19.11%±11.63%; p=0.033). After excluding 8 cancer patients who received chemotherapy before sperm banking, sperm concentration, sperm total motility, and sperm progressive motility were significantly lower in cancer patients than in controls, but there was no significant difference in sperm DFI for cancer patients and controls (23.14%±12.79% vs. 19.11%±11.63%; p=0.069). CONCLUSIONS: Sperm quality was lower in cancer patients than in controls. There was no difference in the sperm DFI of cancer patients prior to chemotherapy and men presenting for sperm cryopreservation for ART. We recommend that all men who are planning cancer therapy should be offered sperm banking prior to gonadotoxic chemotherapy as a standard of fertility preservation.

Returning to golf after rotator cuff repair.

Background: The prevalence of rotator cuff repair is increasing; however, no study has assessed patients who have returned to golf activity after arthroscopic rotator cuff repair. Methods: The subjects of the survey were 633 patients who were at least two years postoperative after rotator cuff repair from January 2005 to December 2017. From August 2019 to October 2019, survey responses were collected via an online questionnaire or phone calls and a total of 197 patients were reviewed retrospectively to study about returning to golf after rotator cuff repair. The detailed survey included 12 questions specific to the patient's golf career, performance, time of return to play, and symptoms related to golf activity. Depending on the size of the rotator cuff tear, each question was statistically analyzed to determine whether there were differences in the time of return to golf, uncomfortable symptoms when golfing, and distance of the driving. Results: Of the 197 patients who underwent arthroscopic rotator cuff repair, there were 145 patients (73.6%) returned to golf. In the analysis results of 145 patients, the longer the golf career, the greater the chance of returning to golf. Sixty (30.5%) people returned to golf at 1 year after surgery. Twenty-one patients (10.7%) improved and 46 patients (23.4%) maintained their driving distance, whereas 78 patients (39.6%) had a worse driving distance after surgery. Ten patients (5.1%) improved and 97 patients (49.2%) maintained their golf score, but 38 patients (19.3%) had worse golf scores after surgery. Symptoms when playing golf were reported in the order of no symptoms (62.1%), a limited range of motion (13.1%), muscle weakness (11.1%), and anxious about their operated shoulder (10.3 %). Men were 6.9 times more likely to return to golf than women (odds ratio, 6.9; 95% confidence interval, 3.2-14.8). The younger the age and the shorter the time since surgery, the higher the golfing return rate. The rate of returning to golf was high in the group of patients with good tissue quality during surgery (odds ratio, 3.9; 95% confidence interval, 0.01-2.6). Conclusion: The golfing return rate after arthroscopic rotator cuff repair was higher than expected (73.6%) and most players returned at 1 year after surgery. Especially, in the case of young males, their golf scores were maintained or improved and they were able to return to golf earlier after surgery. Better tissue quality in the intraoperative torn tendon was associated with a greater chance of returning to golf.

Global Trends in Social Prescribing: Web-Based Crawling Approach.

BACKGROUND: Social loneliness is a prevalent issue in industrialized countries that can lead to adverse health outcomes, including a 26% increased risk of premature mortality, coronary heart disease, stroke, depression, cognitive impairment, and Alzheimer disease. The United Kingdom has implemented a strategy to address loneliness, including social prescribing-a health care model where physicians prescribe nonpharmacological interventions to tackle social loneliness. However, there is a need for evidence-based plans for global social prescribing dissemination. OBJECTIVE: This study aims to identify global trends in social prescribing from 2018. To this end, we intend to collect and analyze words related to social prescribing worldwide and evaluate various trends of related words by classifying the core areas of social prescribing. METHODS: Google's searchable data were collected to analyze web-based data related to social prescribing. With the help of web crawling, 3796 news items were collected for the 5-year period from 2018 to 2022. Key topics were selected to identify keywords for each major topic related to social prescribing. The topics were grouped into 4 categories, namely Healthy, Program, Governance, and Target, and keywords for each topic were selected thereafter. Text mining was used to determine the importance of words collected from new data. RESULTS: Word clouds were generated for words related to social prescribing, which collected 3796 words from Google News databases, including 128 in 2018, 432 in 2019, 566 in 2020, 748 in 2021, and 1922 in 2022, increasing nearly 15-fold between 2018 and 2022 (5 years). Words such as health, prescribing, and GPs (general practitioners) were the highest in terms of frequency in the list for all the years. Between 2020 and 2021, COVID, gardening, and UK were found to be highly related words. In 2022, NHS (National Health Service) and UK ranked high. This dissertation examines social prescribing-related term frequency and classification (2018-2022) in Healthy, Program, Governance, and Target categories. Key findings include increased "Healthy" terms from 2020, "gardening" prominence in "Program," "community" growth across categories, and "Target" term spikes in 2021. CONCLUSIONS: This study's discussion highlights four key aspects: (1) the "Healthy" category trends emphasize mental health, cancer, and sleep; (2) the "Program" category prioritizes gardening, community, home-schooling, and digital initiatives; (3) "Governance" underscores the significance of community resources in social prescribing implementation; and (4) "Target" focuses on 4 main groups: individuals with long-term conditions, low-level mental health issues, social isolation, or complex social needs impacting well-being. Social prescribing is gaining global acceptance and is becoming a global national policy, as the world is witnessing a sharp rise in the aging population, noncontagious diseases, and mental health problems. A successful and sustainable model of social prescribing can be achieved by introducing social prescribing schemes based on the understanding of roles and the impact of multisectoral partnerships.

Bamboo Salt and Triple Therapy Synergistically Inhibit Helicobacter pylori-Induced Gastritis In Vivo: A Preliminary Study.

Helicobacter pylori infections are a major cause of gastrointestinal disorders, including gastric ulcers, gastritis, and gastric cancer. Triple therapy, using two antibiotics and a proton pump inhibitor, is recommended for the treatment of H. pylori infections. However, antibiotic resistance in H. pylori is an emerging issue. Bamboo salt, a traditional Korean salt made by baking solar sea salt in bamboo barrels, can ameliorate the symptoms of various gastrointestinal diseases. Herein, we compared the anti-H. pylori activity of triple therapy (clarithromycin, metronidazole, and omeprazole), solar salt, and bamboo salt in vivo as a preliminary study. Four-week-old C57BL/6 male mice were inoculated for eight weeks with the H. pylori Sydney Strain 1 (SS-1) and orally administered triple therapy drugs and salts for five days. The transcript levels of the H. pylori-expressed gene CagA and inflammatory cytokines Tnfα and Il-1ß significantly decreased in the bamboo salt treated mice than those in the H. pylori-infected control group. This effect was further enhanced by using triple therapy and bamboo salt together. Solar salt caused modest inhibition of H. pylori-induced inflammation. We also demonstrated the synergistic effects of bamboo salt and triple therapy against H. pylori. Thus, bamboo salt may be a potential candidate agent against the treatment of H. pylori-associated gastritis.

Development of fermented rice cake containing strawberry showing anti-inflammatory effect on LPS-stimulated macrophages and paw edema induced mice.

Strawberry (Fragaria ananassa) is one of the richest sources containing a wide variety of nutritive compounds. Anti-inflammatory activities of fermented rice cake made of strawberry powder as well as rice powder were evaluated. The fermented rice cake containing strawberry powder (SRC) significantly and dose-dependently inhibited NO production in LPS-stimulated RAW264.7 cells without cytotoxicity. Also, SRC effectively suppressed inflammatory gene expression, including iNOS, COX-2, IL-1ß, IL-6, and TNF-α. In addition, the production of PGE2, IL-1ß, IL-6, and TNF-α was significantly reduced. Furthermore, the anti-inflammatory effect of SRC was investigated using carrageenan-induced paw edema of ICR mice. It was demonstrated that pre-orally administration of SRC at a dose of 50 and 100 mg/kg BW significantly inhibited paw edema induced by carrageenan. This study suggested that the anti-inflammation activities of strawberry rice cake give the potential for increasing the commercialization of rice cake and rice products.

Graft isometry during anatomical ACL reconstruction has little effect on surgical outcomes.

PURPOSE: To investigate the surgical outcomes of anatomical anterior cruciate ligament (ACL) reconstruction according to the graft isometry measured during surgery. METHODS: Electrical medical records of patients who underwent an arthroscopic ACL reconstruction through the transportal technique using hamstring tendon autograft between 2012 and 2016 were retrospectively reviewed. The patients were classified into two groups based on the graft length change throughout the knee range of motion measured just before graft fixation (Group 1, graft length change ≤ 2 mm; Group 2, graft length change > 2 mm). Comparative analyses, including a non-inferiority trial, were performed regarding the clinical scores, knee laxity, and radiographic parameters between the groups. RESULTS: A total of 67 patients were included in the study. The total change in the length of ACL graft throughout the knee range of motion was 1.4 ± 0.4 mm in Group 1 (range, 0.2-2.0 mm), and 3.0 ± 0.7 mm in Group 2 (range, 2.2-5.0 mm). Group 1 showed a relatively high (proximal) femoral tunnel and shallow (anterior) tibial tunnel compared to Group 2 (P < 0.001 and P = 0.028, respectively), but there were no apparent differences in the macroscopic view. There were no statistically significant differences in the clinical outcomes between groups at 2 years after surgery, which satisfied the non-inferiority criterion of Group 1 in terms of clinical scores and knee laxity compared to Group 2. CONCLUSION: The surgical outcomes of anatomical ACL reconstruction in patients with non-isometric ACL graft were not inferior in terms of clinical scores and knee laxity, compared to those with nearly-isometric ACL graft. The graft tunnel placement in the isometric position during anatomical ACL reconstruction, which is technically challenging in the clinical setting, is not a crucial factor in terms of clinical outcomes. LEVEL OF EVIDENCE: Level IV.

Induction of IL-6Rα by ATF3 enhances IL-6 mediated sorafenib and regorafenib resistance in hepatocellular carcinoma.

Sorafenib and its derivative regorafenib are the first- and second-line targeted drugs for advanced HCC, respectively. Although both drugs improve overall survival, drug resistance remains the major barrier to their full efficacy. Thus, strategies to enhance sorafenib and regorafenib efficacy against HCC are solely needed. Interleukin-6 receptor alpha (IL-6Rα) is the receptor of IL-6, a multi-functional cytokine, which plays key roles in liver-regeneration, inflammation and development of hepatocellular carcinoma (HCC). Here we show the expression of IL-6Rα was induced in response to sorafenib. Depletion of IL-6Rα abolished IL-6 induced STAT3 phosphorylation at 705th tyrosine and tumor growth of HCC cells under sorafenib treatment. Mechanistically, activating transcription factor 3 (ATF3) was induced in response to sorafenib and subsequently bound to the promoter of IL-6Rα, leading to its transcriptional activation. Depletion of ATF3 or its upstream transcription factor, ATF4, attenuated IL-6Rα induction and IL-6 mediated sorafenib resistance. The ATF4-ATF3-IL-6Rα cascade is also activated by regorafenib. Furthermore, blockade of IL-6Rα with the FDA approved IL-6Rα antibody drug, Sarilumab, drastically attenuated both sorafenib and regorafenib resistance in patient-derived xenograft (PDX) tumors, where human IL-6 could be detected by a novel in situ hybridization technique, named RNAscope. Together, our data reveal that ATF3-mediated IL-6Rα up-regulation promotes both sorafenib and regorafenib resistance in HCC, and targeting IL-6Rα represents a novel therapeutic strategy to enhance sorafenib/regorafenib efficacy for advanced HCC treatment.

Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by notorious resistance to current therapies attributed to inherent tumor heterogeneity and highly desmoplastic and immunosuppressive tumor microenvironment (TME). Unique proline isomerase Pin1 regulates multiple cancer pathways, but its role in the TME and cancer immunotherapy is unknown. Here, we find that Pin1 is overexpressed both in cancer cells and cancer-associated fibroblasts (CAFs) and correlates with poor survival in PDAC patients. Targeting Pin1 using clinically available drugs induces complete elimination or sustained remissions of aggressive PDAC by synergizing with anti-PD-1 and gemcitabine in diverse model systems. Mechanistically, Pin1 drives the desmoplastic and immunosuppressive TME by acting on CAFs and induces lysosomal degradation of the PD-1 ligand PD-L1 and the gemcitabine transporter ENT1 in cancer cells, besides activating multiple cancer pathways. Thus, Pin1 inhibition simultaneously blocks multiple cancer pathways, disrupts the desmoplastic and immunosuppressive TME, and upregulates PD-L1 and ENT1, rendering PDAC eradicable by immunochemotherapy.

Strain hardening recovery mediated by coherent precipitates in lightweight steel.

We investigated the effect of κ-carbide precipitates on the strain hardening behavior of aged Fe-Mn-Al-C alloys by microstructure analysis. The κ-carbides-strengthened Fe-Mn-Al-C alloys exhibited a superior strength-ductility balance enabled by the recovery of the strain hardening rate. To understand the relation between the κ-carbides and strain hardening recovery, dislocation gliding in the aged alloys during plastic deformation was analyzed through in situ tensile transmission electron microscopy (TEM). The in situ TEM results confirmed the particle shearing mechanism leads to planar dislocation gliding. During deformation of the 100 h-aged alloy, some gliding dislocations were strongly pinned by the large κ-carbide blocks and were prone to cross-slip, leading to the activation of multiple slip systems. The abrupt decline in the dislocation mean free path was attributed to the activation of multiple slip systems, resulting in the rapid saturation of the strain hardening recovery. It is concluded that the planar dislocation glide and sequential activation of slip systems are key to induce strain hardening recovery in polycrystalline metals. Thus, if a microstructure is designed such that dislocations glide in a planar manner, the strain hardening recovery could be utilized to obtain enhanced mechanical properties of the material.

Low Expression of EphB2, EphB3, and EphB4 in Bladder Cancer: Novel Potential Indicators of Muscular Invasion.

PURPOSE: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer. MATERIALS AND METHODS: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. RESULTS: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells. CONCLUSION: Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.

The Graft Insertion Length in the Femoral Tunnel During Anterior Cruciate Ligament Reconstruction With Suspensory Fixation and Tibialis Anterior Allograft Does Not Affect Surgical Outcomes but Is Negatively Correlated With Tunnel Widening.

PURPOSE: To investigate the surgical outcomes of anterior cruciate ligament (ACL) reconstruction using a low-dose irradiated tibialis anterior allograft with a fixed-loop cortical suspension device for the femur based on the graft insertion length (GIL) in the femoral tunnel. METHODS: Between January 2010 and January 2018, the medical records of consecutive patients who underwent arthroscopic ACL reconstruction with a tibialis anterior allograft fixed with the EndoButton CL for the femur and who had at least 2 years of follow-up were retrospectively evaluated. Patients were classified into 3 groups based on the GIL in the femoral tunnel (group 1, GIL < 15 mm; group 2, GIL of 15-20 mm; and group 3, GIL > 20 mm), and their functional scores, knee laxity, and radiographic parameters were evaluated. RESULTS: A total of 91 patients were analyzed. There were no statistically significant differences in the functional scores and knee laxity between the 3 groups at 2 years postoperatively. However, significant differences were observed in tunnel widening at 1 year postoperatively in the femur (P = .045 for absolute value and P = .004 for relative value) and the tibia (P = .014 for absolute value and P = .012 for relative value), revealing that both the femoral and tibial tunnels widened as the GIL decreased. Additional linear regression analyses were performed to identify whether the GIL independently affects tunnel widening. Consequently, the femoral tunnel depth, tunnel diameter, and GIL were found to independently influence femoral tunnel widening (P = .008, P = .019, and P < .001, respectively), whereas the tunnel diameter and GIL affected tibial tunnel widening (P < .001 and P = .004, respectively). CONCLUSIONS: The GIL in the femoral tunnel during ACL reconstruction using a tibialis anterior allograft with a fixed-loop cortical suspension device for the femur has no significant association with the postoperative functional outcomes and knee laxity, but it has a negative correlation with tunnel widening in the femur and the tibia. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Clinical Impact of Natural Killer Group 2D Receptor Expression and That of Its Ligand in Ovarian Carcinomas: A Retrospective Study.

PURPOSE: Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically. RESULTS: ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival. CONCLUSION: High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.

Mild to Moderate Varus Alignment in Relation to Surgical Repair of a Medial Meniscus Root Tear: A Matched-Cohort Controlled Study With 2 Years of Follow-up.

BACKGROUND: Increased varus alignment of the lower extremity is known to be a poor prognostic factor for the surgical repair for a medial meniscus root tear (MMRT). However, given the concept of constitutional varus, which is present in a substantial portion of the normal population, the generally accepted surgical indication for MMRT concerning a varus alignment of 5° may be unnecessarily narrow. PURPOSE: To compare the surgical outcomes of arthroscopic transtibial pullout repair of MMRT according to the degree of varus alignment of the lower extremity. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent isolated arthroscopic transtibial pullout repair of MMRT between January 2010 and July 2017 at one institution and had a minimum follow-up of 2 years were included in this study. Patients were classified into 1 of 2 groups: the experimental group (n = 22) included patients with a preoperative hip-knee-ankle angle between 5° and 10° varus (mild to moderate varus alignment) and the control group (n = 51) included those with a preoperative hip-knee-ankle angle <5° varus (neutral alignment). Clinical scores and radiographic parameters were compared between the groups to assess surgical outcomes, which were statistically matched for potential confounders (age, body mass index, the severity of cartilage lesion) by use of the inverse probability of treatment weighting. A noninferiority trial was performed comparing the experimental and control groups in terms of subjective outcomes (International Knee Documentation Committee subjective and Lysholm scores) and objective outcomes (postoperative medial meniscal extrusion and the rate of osteoarthritis progression). RESULTS: There were no statistically significant differences in surgical outcomes between the groups in subjective and objective aspects, which were consistent before and after inverse probability of treatment weighting. Apart from the clinical improvement observed in both groups, overall degenerative changes in the knee were found, although progression rates did not differ between the groups. In terms of the noninferiority trial, the overall surgical outcomes in the experimental group were not inferior to those in the control group. CONCLUSION: The short-term surgical outcomes of arthroscopic transtibial pullout repair for MMRT of patients with mild to moderate varus alignment were not inferior to but rather comparable with those with neutral alignment in terms of subjective and objective aspects. Therefore, it would be inappropriate to exclude patients with a diagnosis of MMRT from being indicated for the surgery simply because of mild to moderate varus alignment.

An Increase in Medial Joint Space Width After Medial Open-Wedge High Tibial Osteotomy Is Associated With an Increase in the Postoperative Weight-Bearing Line Ratio Rather Than With Cartilage Regeneration: Comparative Analysis of Patients Who Underwent Second-Look Arthroscopic Assessment.

PURPOSE: To investigate relevant factors influencing increases in medial joint space width (JSW) after medial open-wedge high tibial osteotomy (MOWHTO). METHODS: Between January 2010 and December 2018, the electronic medical records of consecutive patients who underwent MOWHTO and subsequent second-look arthroscopic assessment at least 12 months after MOWHTO were retrospectively evaluated. The patients were classified into 2 groups according to changes in the medial JSW of the knee at the time of the second-look operation compared with that at baseline before the initial surgical procedure. Various radiographic parameters, arthroscopic findings, and clinical scores were compared between the groups, and regression analysis was performed to identify factors related to increases in medial JSW. RESULTS: A total of 114 patients were analyzed. In a bivariate analysis, patients who experienced an increase in medial JSW showed a significantly higher postoperative weight-bearing line ratio (WBLR) (P = .008) and a greater proportion of severe preoperative cartilage lesions in the medial compartment of the knee compared with patients with a maintained or reduced medial JSW (P = .035). In terms of clinical scores, patients with an increased medial JSW showed relatively favorable clinical outcomes at the time of the second-look operation. Regression analysis indicated only postoperative WBLR as a relevant factor associated with an increase in medial JSW after MOWHTO (odds ratio, 1.057; P = .01). Additional analysis with patients reclassified according to the postoperative WBLR showed that as the postoperative WBLR increased, the medial JSW increased, without a significant change in the lateral JSW. CONCLUSIONS: An increase in the medial JSW of the knee joint after MOWHTO appears to be associated with an increase in the postoperative WBLR, not with cartilage regeneration. Obtaining adequate correction so that the postoperative WBLR is within 60% to 70% would be desirable in terms of postoperative changes in the medial JSW, as well as clinical outcomes. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

The Natural History of High-Grade Partial Thickness Rotator Cuff Tears: The Conversion Rate to Full Thickness Tears and Affecting Factors.

BACKGROUND: Information regarding the progression of high-grade partial thickness rotator cuff tears (PTRCTs) is scarce. We aimed to assess the clinical outcome and the conversion rate to full thickness tears in patients with high-grade PTRCTs who underwent nonoperative treatment and to determine the factors associated with tear progression. METHODS: A total of 52 patients with high-grade PTRCTs, which were detected by magnetic resonance imaging or ultrasonography (USG), were treated conservatively between 2010 and 2017. They were followed up with USG at 6- to 12-month intervals for a mean of 34 months (range, 12-105 months). The average patient age was 57 years (range, 34-70 years), and 34 patients were women. Age, sex, body mass index, arm dominance, symptom duration, subscapularis tendon involvement, tear location, and trauma history were compared between patients with and without conversion to full thickness tears. RESULTS: A substantial percentage of high-grade PTRCTs progressed to full thickness tears (16/52, 30.8%). According to Kaplan-Meier analysis, the full thickness conversion rate was 30.8% at 3 years and 64% at 4 years. The full thickness conversion rate was higher in patients with subscapularis tendon involvement (p = 0.012). CONCLUSIONS: A considerably large proportion of high-grade PTRCTs progressed to full thickness tears. Therefore, regular monitoring of tear progression should be considered after conservative treatment of high-grade PTRCTs, particularly in patients with subscapularis tendon involvement.