Tachol1 QTL on mouse chromosome 1 is responsible for hypercholesterolemia and diet-induced obesity.

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.

Longer peripheral-track lesions are associated with instability after arthroscopic Bankart repair.

BACKGROUND: The glenoid track concept has enabled the categorization of Hill-Sachs lesions (HSLs) into on-track lesions and off-track lesions. Furthermore, among the on-track lesions, further categorization has been established based on the distance from the medial edge of the Hill-Sachs lesion to the medial edge of the glenoid track, into peripheral-track lesions and central-track lesions. Recent studies on peripheral-track lesions and central-track lesions within the glenoid track have shown inconsistencies in failure rates, which deserves further investigation. METHODS: A retrospective cohort comparison of patients who underwent arthroscopic Bankart repair between 2015 and 2020 was performed. 102 patients with peripheral-track HSLs were included. The patients were divided into 2 groups based on the results of the postoperative apprehension test: the apprehension positive group (n = 30), and the apprehension negative group (n = 72). Using preoperative computed tomography (CT) and an image reconstruction program, 3-dimensional (3D) images were segmented to calculate the length, width, depth, and distance of the HSLs. A multivariate logistic regression was used to determine the risk factors of recurrence, for which odds ratio (OR) and 95% confidence interval (CI) were provided. RESULTS: A multivariate logistic regression analysis revealed that the length of the peripheral-track HSLs was a significant independent predictor of failure in this study. (OR 1.380; 95% CI 1.170-1.627; P < .001). The receiver operating characteristics curve (ROC) demonstrated a predictive power (area under the curve = 0.841) and a threshold value of 14.2 mm. CONCLUSION: Length was the only risk factor for the recurrent instability of peripheral-track HSLs after ABR. In the context of surgical decision-making, utilizing the glenoid track concept, medical practitioners may need to evaluate instability by considering the length as a continuous factor, while differentiating between peripheral-track and central-track classifications.

Serial Changes of Fatty Degeneration and Clinical Outcomes after Repair of Medium-Sized Rotator Cuff Tears.

Background: This study was designed to longitudinally analyze quantitative intramuscular and perimuscular fat and evaluate clinical outcomes according to healing degree after rotator cuff repair. Methods: From June 2013 through October 2018, patients who had undergone repair due to medium-sized rotator cuff tears and serial chest computed tomography (CT) preoperatively and at early (6-12 months) and late (at least 3 years) postoperative follow-ups were included. Supraspinatus (SST) intramuscular fat fraction ratio (IFFR) and perimuscular fat fraction ratio (PFFR) were calculated using chest CT. The rotator cuff integrity was categorized as healed, smaller retear (SRT), and larger retear (LRT) by comparing the preoperative tear size and retear size in shoulder CT arthrography at postoperative follow-ups. Clinical outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder rating scale, and the Constant score preoperatively and at early and late postoperative follow-ups. Results: In the LRT group, compared with the preoperative values, there were increases in the SST IFFR and PFFR at the early (p = 0.002 and p = 0.006, respectively) and late (p < 0.001 and p < 0.001, respectively) postoperative time points. Late postoperative clinical scores (UCLA and Constant scores) were not improved compared to preoperative scores (p = 0.156 and p = 0.094, respectively). In the SRT group, there was no difference in the mean SST IFFR and PFFR between preoperative and early postoperative time points (p = 0.766 and p = 0.180, respectively), but the late postoperative values were higher than preoperative values (p = 0.009 and p = 0.049, respectively). Late postoperative clinical scores (ASES, UCLA, and Constant scores) in the SRT group improved compared to preoperative time (p < 0.001, p < 0.001, and p = 0.016, respectively). In the healed group, compared with the preoperative values, there was no difference in the mean SST IFFR and PFFR at postoperative time points; however, the late postoperative clinical scores (ASES, UCLA, and Constant scores) were improved (all p < 0.001). Conclusions: In the SRT group, IFFR and PFFR progressed in the late postoperative period and clinical scores improved over time. However, in the LRT group, IFFR and PFFR progressed in the early and late postoperative periods and clinical scores did not improve at the late postoperative follow-up.

Patterns of Anterior Inferior Tibiofibular Ligament Avulsion Fracture Accompanied by Ankle Fracture.

The anterior inferior tibiofibular ligament (AITFL) avulsion fracture accompanying an ankle fracture can compromise ankle stability, necessitating accurate evaluation and a clear understanding of its pathophysiology.. The aim of this study was to investigate the association between AITFL avulsion fracture and Lauge-Hansen, Wagstaffe classification. A retro-prospective study was conducted at a university-affiliated tertiary care medical center. We selected 128 patients who underwent surgery at our institution between January 2013 and July 2017 and analyzed the association between AITFL avulsion fracture and the foot position. According to the modified Wagstaffe classification system, there were 39 cases of type II, followed by 9 cases of type III and 8 cases of type IV. Of the7 pronation-abduction fractures, 3 were AITFL avulsion fracture (43%), while of the 21 pronation-external rotation fractures, 9 were AITFL avulsion fracture (43%). Of the 95 supination-external rotation fractures, there were 56 cases (59%) of AITFL avulsion fractures. Of the pronation fractures, 0% were fibular avulsion fractures and 43% were tibial avulsion fractures. Of the supination fractures, 44% were fibular avulsion fractures and 16% were tibial avulsion fracture. The difference in the ratio of fibular to tibial avulsion fractures between pronation and supination fractures was significant (p < .001). These results suggest that tibial avulsion fractures of type IV in the modified Wagstaffe classification and pronation fractures occur due to collision with the anterolateral corners of the distal bone when the talus externally rotates. Moreover, in cases of pronation fractures, a new type of AITFL avulsion fracture has been observed.

Association of clinical manifestations of secondary lymphedema and lymph node dissection sites in the lower extremities of patients with melanoma.

BACKGROUND: Lymphedema is a chronic, debilitating disease that often requires life-long management. Predicting clinical manifestations and prognosis is crucial in clinical practice because the treatment of lymphedema should be individualized for best clinical outcome. The aim of this study is to explore the location and severity of lymphedema secondary to inguinal and/or iliac lymph node dissection (LND) in patients with melanoma. METHODS: Patients with melanoma who received LND at a single tertiary medical center between 1 January 2010 and 31 September 2022 were retrospectively reviewed. Patient who received inguinal LND only were designate as the inguinal group while those who received both ilioinguinal LND were included in the ilioinguinal group. Volumetric measurement was used to objectify the severity and location of lymphedema. Clinical data was acquired for 12-15 months of follow-up. RESULTS: Among 81 patients, 43 (53%) had developed lymphedema in the lower extremities at an average of 33 days after the surgery. Initially, patients manifested with medial thigh lymphedema in the inguinal group while patients were presented with whole leg lymphedema in the ilioinguinal group. Lower leg volume of the ilioinguinal group was significantly higher than the inguinal group. After more than 12 months of lymphedema treatment, upper leg volume was higher in the ilioinguinal group than the inguinal group (12.7% vs 5.4%, p < 0.05). CONCLUSION: Lymphedema developed in early post-op period. The ilioinguinal group presented with a larger volume of lymphedema in the distal area of the legs. Even after sufficient treatment, predominant lymphedema remained in the proximal leg for the ilioinguinal group. Patients with both inguinal and iliac LND were associated with more severe lymphedema. Based on the dissection sites, the clinical manifestations and prognosis of leg lymphedema can vary widely. Thus, clinicians should consider the dissection site when approaching melanoma patients with lymphedema.

Preoperative identification of low-risk medullary thyroid carcinoma: potential application to reduce total thyroidectomy.

Current guidelines recommend total thyroidectomy with central lymph node dissection (CND) for patients with medullary thyroid carcinoma (MTC). This study aimed to identify low-risk MTC patients who may be candidates for lobectomy. We retrospectively reviewed MTC patients who underwent primary surgery at a tertiary referral center from 1998 to 2019. Eighty-five MTC patients were enrolled, excluding patients with primary tumor size > 2.0 cm. Among them, one (1.2%) patient had bilateral tumors. During a median follow-up of 84 months, 12 of the 85 patients experienced structural recurrence. 13 patients had occult lymph node metastasis, and structural recurrence occurred in 2 patients. Factors that significantly affected disease-free survival were clinical N stage (cN0 vs. cN1, log-rank P < 0.001), pathological N stage (pN0 vs. pN1, P < 0.001), and preoperative calcitonin levels (≤ 250 vs. > 250 pg/mL, P = 0.017). After categorizing patients into four groups, patients with preoperative calcitonin levels > 250 pg/mL and cN1 or pN1 had a significantly worse prognosis. Patients with a primary tumor size of 2 cm or less, cN0, and preoperative calcitonin of 250 pg/mL or less can be classified as low-risk MTC patients. We used preoperative clinical information to identify low-risk MTC patients. Lobectomy with prophylactic CND may be a potential therapeutic approach.

miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells.

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Influence of joint volume on range of motion after arthroscopic rotator cuff repair.

BACKGROUND: Capsular contracture is a well-known etiology in the primary stiff shoulder; thus capsular contracture and resultant decreased joint volume could lead to postoperative stiffness, which is a commonly reported morbidity after arthroscopic rotator cuff repair (ARCR). The purpose of this study was (1) to quantify the joint volume (total joint volume and each quadrant compartmental volume) using computed tomography arthrography (CTA) and (2) to demonstrate the relationship between joint volume and postoperative range of motion (ROM) after ARCR. MATERIALS AND METHODS: Eighty-three patients (60 ± 5.11 years, men = 26, women = 57) who had undergone ARCR between January 2015 to December 2020 due to small to medium full-thickness tear and followed by CTA 6 months postoperatively were retrospectively reviewed. An image reconstruction program (3D Slicer, version 4.11.2 software) was used to calculate the joint volume (total joint volume and quadrant compartment joint volumes; anteroinferior, anterosuperior, posterosuperior and posteroinferior). For shoulder ROM, data including scaption (Sc), external rotation on side (ERs), external rotation at 90° (ER90), and internal rotation on back (IRb) were collected 6 months postoperatively. An evaluation of the correlation between joint volume and each shoulder motion was performed. RESULTS: There were moderate correlations between the total joint volume and each motion (Sc: Pearson coefficient, 0.32, p = 0.0047; ERs: Pearson coefficient, 0.24, p = 0.0296; ER90: Pearson coefficient, 0.33, p = 0.0023; IRb: Pearson coefficient, 0.23, p = 0.0336). Among the quadrant compartments, the anteroinferior (Sc: Pearson coefficient, 0.26, p = 0.0199; ERs: Pearson coefficient, 0.23, p = 0.0336; ER90: Pearson coefficient, 0.25, p = 0.0246; IRb: Pearson coefficient, 0.26, p = 0.0168) and posterosuperior (Sc: Pearson coefficient, 0.24, p = 0.029; ER90: Pearson coefficient, 0.29, p = 0.008; IRb: Pearson coefficient, 0.22, p = 0.0491) and posteroinferior (Sc: Pearson coefficient, 0.30, p = 0.0064; ER90: Pearson coefficient, 0.29, p = 0.0072) showed moderate correlations with each shoulder motion. CONCLUSION: Total joint volume, anteroinferior compartment joint volume, posterosuperior compartment joint volume and posteroinferior compartment joint volume were related to postoperative ROM after ARCR. Perioperative methods to increase the joint volume, especially the anteroinferior, posterosuperior and posteroinferior parts of the capsule may prevent postoperative stiffness after ARCR. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Study.

Association between urinary iodine concentration and the risk of papillary thyroid cancer by sex and age: a case-control study.

Previous studies on dietary iodine intake and the risk of papillary thyroid cancer (PTC) have demonstrated inconsistent results. We aimed to evaluate the association between urinary iodine concentration (UIC), a surrogate biomarker for dietary iodine intake, and the risk of thyroid cancer stratified by sex and age in an iodine-sufficient area. A hospital-based case-control study was conducted in Seoul, South Korea. A total of 492 cases of newly diagnosed PTC and 595 controls were included. Compared with the lowest quartile of creatine-adjusted UIC (< 159.3 µg/gCr), the highest quartile (≥ 1037.3 µg/gCr) showed an increased risk of PTC (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.04-2.13), especially in those who were < 45 years old (ptrend = 0.01) compared with those who were ≥ 45 years old (ptrend = 0.48). For those who were < 45 years old, a positive association between creatinine-adjusted UIC and the risk of PTC was observed in both men (q4 vs. q1, OR 4.27, 95% CI 1.14-18.08) and women (OR 1.97, 95% CI 1.04-3.78). For those who were ≥ 45 years old, no association was found in any sex. Creatinine-adjusted UIC was positively associated with the risk of PTC, especially in those who were younger than 45 years for both men and women.

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

BACKGROUND: A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial. OBJECTIVE: The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation. METHODS: A total of 87 FTC patients who had information about TERT promoter mutation from August 1995 to November 2020 were investigated. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each of the World Health Organization (WHO) 2017 classifications were calculated. RESULTS: Of the 87 patients, 8 (9.2%) had initial distant metastasis and 15 (17.2%) had persistent disease or developed structural recurrence. The threshold diameter for initial distant metastasis, disease recurrence, and cancer-specific death was 2 cm in minimally invasive FTC (MI-FTC) with mutant TERT (M-TERT) and in encapsulated angioinvasive FTC (EA-FTC) with M-TERT, while that in MI-FTC with wild-type TERT (WT-TERT) and EA-FTC with WT-TERT was 4 cm. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each WHO 2017 classification was significantly different only in patients with WT-TERT (p = 0.001, p = 0.019, and p = 0.005, respectively). CONCLUSIONS: The data suggest 2 cm as a critical threshold diameter for performance of completion thyroidectomy in MI-FTC with M-TERT and EA-FTC with M-TERT. TERT promoter mutational status can help select candidates for completion thyroidectomy.

Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen.

PURPOSE: To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen. METHODS: This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included. Disease assessment was performed every 6 weeks. RESULTS: A total of 185 patients were included (males, 58.9%; right-sided tumors, 23.8%; and ECOG performance factor ≥ 1, 68.6%). A total of 514 adverse events (AEs) occurred in 134 patients, of which 206 (49.2%; 95% CI 42.0%, 56.4%) events were considered as adverse drug reactions (ADRs), 172 unexpected AEs (49.7%; 95% CI 42.5%, 56.9%), and 53 serious AEs (22.2%; 95% CI16.2%, 28.2%). The most common serious ADR was pneumonia (n = 2, 1.6%). The most common all grade hematological AE and non-hematological AE were neutropenia (21.6%) and nausea (16.2%), respectively. Over a median follow-up of 5.6 months, a total of five grade 5 (1.0%) AEs were reported. Median OS was 9.4 months, and median progression-free survival (PFS) was 7.3 months. The overall response rate was 14.6%. Right-sided tumor location and prior bevacizumab treatment were independent factors of poor PFS in multivariate analysis. CONCLUSION: Aflibercept in combination with FOLFIRI was effective and showed an acceptable safety profile in Korean patients with mCRC in daily clinical practice.

Parameters affecting improvement of excessive daytime sleepiness in obstructive sleep apnea patients.

OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder caused by repetitive obstruction of the upper airway; this impairs gaseous exchange, resulting in hypoxia, hypercapnia, and frequent arousals. Excessive daytime sleepiness (EDS) is a common daytime symptom of OSA. EDS manifests as fatigue and impaired attention, leading to poor performance at work and falling asleep while driving, which is a major socioeconomic problem. Therefore, it is important to properly treat EDS and accurately predict the response to treatment. However, few studies have compared OSA patients showing and not showing improvement in EDS. Therefore, this study aimed to objectively analyze and compare EDS improvement and non-improvement groups. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 57 OSA patients with EDS. Patients were divided into two groups according to the improvement in EDS after positive airway pressure (PAP) device treatment. We analyzed differences in clinical records including patients' age, sex, history of smoking, hypertension, diabetes, myocardial infarction, and cerebrovascular disease between the two groups. Systolic, diastolic blood pressure, blood test including blood glucose, total cholesterol, high- and low-density lipoprotein cholesterol, and triglyceride levels were also analyzed. Polysomnography (PSG) data, PAP device treatment compliance and scores of questionnaires related to various psychiatric symptoms, subjective sleep quality between the two groups were also analyzed. RESULTS: There was no statistically significant difference in age, gender, or past medical history between the two groups. Systolic and diastolic blood pressure, and blood test results, were also not significantly different. Among the questionnaires related to various psychiatric symptoms, the groups showed statistically significant differences in Social Avoidance and Distress Scale (SADS) and Fear of Negative Evaluation (FNE) scores (P = 0.001 and 0.020, respectively). The group differences in the scores on the other questionnaires were not significantly different. Among the PSG items, significant group differences were observed in the percentage of stage 2 non-REM sleep (N2%, P = 0.023), apnea index (AI, P = 0.005), apnea-hypopnea index (AHI, P = 0.023), and frequency of 3 % oxygen desaturation (ODI3, P = 0.001). No obesity-related parameters showed significant group differences. The percentage of days on which a PAP device was used (out of 90 days; PAP%) and percentage of days on which a PAP device was used for >4 h (Time4%) did not differ significantly. CONCLUSIONS: The SADS, FNE, AI, AHI, N2%, and ODI3 parameters differed significantly between the EDS improvement and non-improvement groups. These parameters may help clinicians treat and predict the prognosis of patients suffering with EDS.

Optimal value of lymph node ratio and metastatic lymph node size to predict risk of recurrence in pediatric thyroid cancer with lateral neck metastasis.

BACKGROUND: No specific guideline exists for risk stratification based on lymph node (LN) status in pediatric thyroid cancer. The purpose of our study is to identify optimal values of lymph node ratio (LNR) and largest metastatic LN size for predicting recurrent/persistent disease, especially in children with lateral neck metastasis (N1b). METHODS: We conducted a retrospective study from January 1997 to June 2018 at Samsung Medical Center. A total of 50 papillary thyroid carcinoma (PTC) patients who underwent total thyroidectomy + both central neck dissection (CND) + modified radical neck dissection (MRND) (unilateral or bilateral) was enrolled. RESULTS: The median follow-up duration was 60.8 months (range, 6.2-247 months). The mean age was 14.6 years, and the mean tumor size was 2.9 cm. Mean size of the largest metastatic LN was 1.5 cm. Mean value of central LNR was 0.6, and mean value of lateral LNR was 0.3. Largest metastatic LN size [HR = 2.0 (95% CI 1.0-4.0), p = 0.040] and lateral LNR [HR = 43.6 (95% CI 2.2-871.0), p = 0.014] were significant prognostic factors for recurrence. The optimal combination of lateral LNR and largest metastatic LN size to predict recurrence were 0.3 and 2.5 cm, respectively, with the largest AUC (AUC at 60 months = 77.4) and significant p-value (p = 0.009 and p = 0.021) (Table 3). Kaplan-Meier curves showed significant differences in recurrence-free survival (RFS) rates among four groups (Fig. 2A,2B). CONCLUSIONS: In pediatric PTC patients with N1b, lateral LNR and largest metastatic LN size are significant predictors for recurrence. Children with lateral LNR > 0.3 or any metastatic lymph node > 2.5 cm in the largest dimension have higher risk for recurrence. Children are classified as extensive N1b if lateral LNR > 0.3 or pathologic N1 with largest LN size > 2.5 cm, and vice versa.

Evaluation of Scapula and Humerus Bone Change after Repair of Small- to Medium-Sized Rotator Cuff Tears: Comparison between Healing and Retear Groups Using Three-Dimensional Computed Tomography.

Background: Rotator cuff tendon retears after rotator cuff repair cause glenohumeral joint instability, which results in changes in the glenoid and humerus head. However, limited data are available on the bone change after repair of small- to medium-sized rotator cuff tears. The aim of this study was to evaluate the difference of glenoid and humerus bone changes between healing and retear groups after repair of small- to medium-sized rotator cuff tears. Methods: Among patients who had arthroscopic repair due to small- to medium-sized rotator cuff tears from January 2009 to January 2017, 49 patients who underwent both preoperative and postoperative (at least 3 years after surgery) shoulder computed tomography were enrolled. Using three-dimensional reconstruction program (3D Slicer) and shape analysis program (SlicerSALT), we compared the occurrence and degree of glenoid bone change, glenoid inclination change, retroversion change, and glenoid center, as well as the degree of humerus head change, between the healing and retear groups. Results: The occurrence of glenoid bone change was significantly more common in the retear group than in the healing group (p = 0.026). The degree of bone change in the 11-1 o'clock axial plane and 10-8 o'clock, 11-7 o'clock, and 12-6 o'clock coronal plane and the degree of glenoid inclination change were significantly larger in the retear group than the healing group (p = 0.026, p = 0.026, p = 0.026, p = 0.026, and p = 0.014, respectively), but the average value of glenoid bone change in the retear group was within the range of 0.14 to 1.01 mm for each plane. The mean humeral head change was 5.69 ± 3.67 mm increase in the retear group and 1.27 ± 2.02 mm increase in the healing group. Compared with the healing group, the retear group showed statistically significantly increased humeral head change (p < 0.001). Conclusions: There was difference in glenoid and humerus bone change between the healing and retear groups at midterm follow-up after repair of small- to medium-sized tears. However, considering the measurement bias, the difference between the two groups was within the measurement error range.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1).

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50−2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60−2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Ursodeoxycholic acid inhibits epithelial-mesenchymal transition, suppressing invasiveness of bile duct cancer cells: An in vitro study.

Epithelial-mesenchymal transition (EMT) features are associated with pathological severity in the progression and metastasis of various cancer types, including bile duct cancer (BDC). Our previous study demonstrated that ursodeoxycholic acid (UDCA) blocked the EGFR-MAPK signaling pathway and inhibited the invasion of BDC cells. The present study was performed to determine whether UDCA inhibits EMT and promotes the expression of E-cadherin to inhibit the invasion and aggressiveness of BDC. In addition, the present study aimed to confirm that the primary mechanism of inhibition of EMT by UDCA is related to the EGFR axis. Human extrahepatic BDC cells were cultured. The effect of UDCA on cell proliferation was evaluated using MTT assays. A cell death ELISA kit was used to measure apoptosis, and western blot assays or immunofluorescence staining assays measured the expression levels of various target proteins. The mRNA expression of Slug and ZEB1 was evaluated via reverse transcription-quantitative PCR. The invasiveness of BDC cells was estimated by invasion assays and western blot assays for focal adhesion kinase (FAK). UDCA inhibited the proliferation of BDC cells as effectively as gefitinib (an EGFR inhibitor), and the combination of UDCA and gefitinib revealed an additive effect on the proliferation of cells. UDCA and gefitinib induced apoptosis, and the combination of UDCA and gefitinib demonstrated an additive effect on apoptosis in BDC cells. UDCA restored the E-cadherin expression inhibited by EGF and suppressed N-cadherin expression increased by EGF as effectively as gefitinib. UDCA suppressed the Slug and ZEB1 mRNA expression induced by EGF in BDC cells. UDCA suppressed the invasiveness of BDC cells and FAK expression linked to the invasiveness of BDC. In conclusion, UDCA enhanced E-cadherin expression and suppressed N-cadherin expression through inhibition of the EGF-EGFR axis, contributing to the inhibition of EMT and invasiveness in BDC cells. Therefore, UDCA may be applied as an adjuvant or palliative antineoplastic agent and as a therapeutic option to enhance the effect of other chemotherapeutics.

Large-area vertically aligned 2D MoS2layers on TEMPO-cellulose nanofibers for biodegradable transient gas sensors.

Crystallographically anisotropic two-dimensional (2D) molybdenum disulfide (MoS2) with vertically aligned (VA) layers is attractive for electrochemical sensing owing to its surface-enriched dangling bonds coupled with extremely large mechanical deformability. In this study, we explored VA-2D MoS2layers integrated on cellulose nanofibers (CNFs) for detecting various volatile organic compound gases. Sensor devices employing VA-2D MoS2/CNFs exhibited excellent sensitivities for the tested gases of ethanol, methanol, ammonia, and acetone; e.g. a high response rate up to 83.39% for 100 ppm ethanol, significantly outperforming previously reported sensors employing horizontally aligned 2D MoS2layers. Furthermore, VA-2D MoS2/CNFs were identified to be completely dissolvable in buffer solutions such as phosphate-buffered saline solution and baking soda buffer solution without releasing toxic chemicals. This unusual combination of high sensitivity and excellent biodegradability inherent to VA-2D MoS2/CNFs offers unprecedented opportunities for exploring mechanically reconfigurable sensor technologies with bio-compatible transient characteristics.