Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer.

The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify the acrolein-DNA adduct (8R/S)-3-(2'-deoxyribos-1'-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dGuo, 1) and the lipid peroxidation-related DNA adduct 1,N6-etheno-dAdo (εdAdo, 2) in DNA obtained by oral rinse from 101 Native Hawaiians, 101 Whites, and 79 Japanese Americans. Levels of urinary biomarkers of nicotine, acrolein, acrylonitrile, and a mixture of crotonaldehyde, methyl vinyl ketone, and methacrolein were also quantified. Whites had significantly higher levels of γ-OH-Acr-dGuo than Japanese Americans and Native Hawaiians after adjusting for age and sex. There was no significant difference in levels of this DNA adduct between Japanese Americans and Native Hawaiians, which is not consistent with the high lung cancer risk of Native Hawaiians. Levels of εdAdo were modestly higher in Whites and Native Hawaiians than in Japanese Americans. The lower level of DNA adducts in the oral cells of Japanese American cigarette smokers than Whites is consistent with their lower risk for lung cancer. The higher levels of εdAdo, but not γ-OH-Acr-dGuo, in Native Hawaiian versus Japanese American cigarette smokers suggest that lipid peroxidation and related processes may be involved in their high risk for lung cancer, but further studies are required.

The orientation of the ALL femoral tunnel to minimize collision with the ACL tunnel depends on the need or not of far-cortex drilling.

PURPOSE: To (1) evaluate the optimal drill orientation of the anterolateral ligament (ALL) femoral tunnel to minimize collision with the anterior cruciate ligament (ACL) femoral tunnel during anatomical ACL reconstruction according to the need for far-cortex drilling and (2) investigate the geometric factors that affect tunnel collision secondary to drill orientation of the ALL femoral tunnel. METHODS: A three-dimensional femoral model of patients who underwent anatomical single-bundle ACL reconstruction between 2015 and 2016 was constructed, and the geometric factors were evaluated. Virtual ALL femoral tunnels were created to simulate 45 drilling conditions. For each condition, whether the virtual ALL femoral tunnel and its trajectory violated the femoral cortex and the minimum distance between tunnels was investigated. RESULTS: Thirty-nine subjects were included. Overall violation rates of the femoral cortex by the ALL tunnels and its trajectories were 11.1% (195 of 1755 conditions) and 40.7% (714 of 1755 conditions), respectively. A drilling angle of axial 0° and coronal - 40° showed the longest minimum distance between tunnels without femoral cortex violation by the ALL tunnel (6.3 ± 4.0 mm; collision rate 2.6% [1 of 39 subjects]). With simultaneous consideration of the ALL tunnel's trajectory representing far-cortex drilling, a drill angle of axial 40° and coronal 10° showed the longest minimum distance between tunnels without femoral cortex violation (0.6 ± 3.9 mm; collision rate 38.5% [15 of 39 subjects]). For surgical techniques requiring far-cortex drilling, regression analyses were performed on geometric factors that could affect tunnel collision, which revealed that the sagittal inclination angle of the ACL and the distance between the ACL femoral tunnel's outlet and ALL's femoral attachment were associated with tunnel collision. CONCLUSION: The optimal drill orientations of the ALL femoral tunnel to minimize collision with the ACL femoral tunnel were axial 0° and coronal - 40° for surgical techniques not requiring far-cortex drilling and axial 40° and coronal 10° for techniques requiring far-cortex drilling. For techniques requiring far-cortex drilling, additional adjustment for orientation of the ACL femoral tunnel is required to reduce the risk of tunnel collision. Therefore, an individualized surgical strategy should be applied according to the graft fixation method of the ALL femoral tunnel.

A Pilot Study of Machine Learning-Based Algorithms to Assist Integrated Care for Older Community-Dwelling Adults.

As life expectancy increases, there is a growing consensus on the development of integrated care encompassing the health and daily activities of older adults. In recent years, although the demand for machine learning applications in healthcare has increased, only a few studies have implemented machine learning-based systems in integrated care for older adults owing to the complex needs of older adults and the coarseness of the available data. Our study aims to explore the possibility of implementing machine learning decision-support algorithms in the integrated care of older community-dwelling adults. Our experiment uses secondary data based on the community-based integrated service model. Such data were collected from 511 older adults through 162 assessment items in which tailored services were selected from 18 available services. We implemented four machine learning models: decision tree, random forest, K-nearest neighbors, and multilayer perceptron. The area under the receiver operating characteristic curve results of the four models were decision tree = 0.89, K-nearest neighbors = 0.88, random forest = 0.93, and multilayer perceptron = 0.88. The results suggest that machine learning-based decision-assisting algorithms can improve the quality of tailored services for integrated care with intensive involvement of face-to-face tasks by reducing the simple, repetitive tasks of care managers.

Clinicopathological features of 70 desmoid-type fibromatoses confirmed by ß-catenin immunohistochemical staining and CTNNB1 mutation analysis.

Desmoid-type fibromatosis (DF) is a locally aggressive neoplasm characterized by mutations in the CTNNB1 gene, which encodes the ß-catenin protein. We reviewed 85 cases of DF and performed Sanger sequencing for detecting mutations in CTNNB1 and immunostaining for detecting ß-catenin localization. We included 70 DF samples, of which 56 cases demonstrated nuclear ß-catenin localization and 43 cases harboured CTNNB1 mutations. CTNNB1-mutant DF samples consistently displayed nuclear ß-catenin expression and were derived from larger-sized tumours compared to samples with wild-type CTNNB1. When we further classified DF cases into 2 subgroups based on the type of specimen, excised specimens with nuclear ß-catenin expression frequently displayed CTNNB1 mutation and no statistical correlation between nuclear ß-catenin expression and CTNNB1 mutation was observed in biopsies. When we classified CTNNB1 mutation cases into 2 subgroups (DF with T41A or T41I, and DF with S45F or S45P), T41A or T41I mutations were observed more frequently in males than in females. Additionally, DF tumours harbouring S45F or S45P mutations were located more frequently in the abdominal wall than tumours with T41A or T41I mutations. In conclusion, CTNNB1 mutation correlates with nuclear ß-catenin expression in larger or excised DF tumours, and DF harbouring CTNNB1 mutations manifest variable clinical presentations.

Arthroscopic gel-type autologous chondrocyte implantation presents histologic evidence of regenerating hyaline-like cartilage in the knee with articular cartilage defect.

PURPOSE: To investigate the clinical, radiological, and histological results of arthroscopic gel-type autologous chondrocyte implantation (GACI) in treating chondral defects of the knee. METHODS: This study prospectively examined five males and five females with a mean age of 40.3 ± 10.3 years who underwent arthroscopic GACI between March 2012 and February 2013. The gel comprised a mixture of 1 ml of fibrinogen plus 0.1-0.2 ml of thrombin. The mean size of chondral defect was 2.9 ± 1.2 cm2 (range 1.2-5.4 cm2). International knee documentation committee (IKDC) subjective score, knee injury and osteoarthritis outcome score (KOOS), knee society score, and visual analog scale (VAS) for pain were assessed preoperatively and during regular follow-up examinations performed for up to 5 years postoperatively. Serial magnetic resonance imaging was performed for up to 2 years after the surgery to observe healing, using the modified magnetic resonance observation of cartilage repair tissue (MOCART) score. In eight patients, second-look arthroscopy was performed at 1 year after the implantation to assess the status of treated cartilage, and a portion of regenerated cartilage was harvested for histologic evaluation. RESULTS: The mean VAS score (p = 0.045), IKDC subjective score (p = 0.041), KOOS pain (p = 0.025), KOOS activities of daily living (p = 0.048), and KOOS quality of life (p = 0.029) showed significant improvement at 5 years after the surgery. The modified MOCART evaluation showed that the scores were 59.5 ± 29.4 and 85.0 ± 8.0 at 12 weeks and 2 years after the operation, respectively. Histologic examination demonstrated a mean regenerated cartilage thickness of 3.5 ± 0.8 mm and a mean Oswestry score of 8.2 ± 1.8. Immunohistochemistry analysis showed that the expression of collagen type II was more evident and more evenly distributed than collagen type I in regenerated cartilage. There was a significant correlation between Oswestry score and change in VAS scale from postoperative 2-5 years. CONCLUSIONS: Arthroscopic GACI produces satisfactory clinical and radiologic outcomes, and histologic evaluation confirms sufficient regeneration of hyaline-like cartilage that correlates with improved symptoms. Therefore, it is an acceptable, minimally invasive, and technically simple option for the restoration of cartilage defects of the knee. LEVEL OF EVIDENCE: IV.

Adequate protection rather than knee flexion prevents popliteal vascular injury during high tibial osteotomy: analysis of three-dimensional knee models in relation to knee flexion and osteotomy techniques.

PURPOSE: (1) To analyse popliteal artery (PA) movement in a three-dimensional (3D) coordinate system in relation to knee flexion and high tibial osteotomy (HTO) techniques (lateral closed wedge HTO [LCHTO], uniplane medial open wedge HTO [UP-MOHTO], biplane medial open wedge HTO [BP-MOHTO]) and (2) to identify safe zones of the PA in each osteotomy plane. METHODS: Sixteen knees of patients who underwent magnetic resonance imaging with extension and 90° flexion were used to develop subject-specific 3D knee flexion models. Displacement of the PA during knee flexion was measured along the X- and Y-axis, as was the distance between the posterior tibial cortex and PA parallel to the Y-axis (d-PCA). Frontal plane safety index (FPSI) and maximal axial safe angles (MASA) of osteotomy, which represented safe zones for the osteotomy from the PA injury, were analysed. All measurements were performed along virtual osteotomy planes. Differences among the three osteotomy methods were analysed for each flexion angle using a linear mixed model. RESULTS: The average increments in d-PCA during knee flexion were 1.3 ± 2.3 mm in LCHTO (n.s.), 1.4 ± 1.2 mm in UP-MOHTO (P < 0.0001), and 1.7 ± 2.0 mm in BP-MOHTO (P = 0.015). The mean FPSIs in knee extension were 37.6 ± 5.9%, 46.4 ± 5.8%, and 45.1 ± 8.1% for LCHTO, UP-MOHTO, and BP-MOHTO, respectively. The mean MASA values in knee extension were 45.8° ± 4.4°, 37.3° ± 6.1°, and 38.9° ± 6.5° for LCHTO, UP-MOHTO, and BP-MOHTO, respectively. CONCLUSION: Although the PA moved posteriorly during knee flexion, the small (1.7 mm) increment thereof and inconsistent movements in subjects would not be of clinical relevance to PA safety during HTO. LEVEL OF EVIDENCE: Diagnostic study, Level II.