Structural reconstruction of mouse acute aortic dissection by intravenously administered human Muse cells without immunosuppression.

BACKGROUND: Stanford type B-acute aortic dissection (type B-AAD) is often life-threatening without invasive surgery. Multilineage-differentiating stress enduring cell (Muse cells), which comprise several percent of mesenchymal stem cells (MSCs), are endogenous pluripotent-like stem cells that selectively home to damaged tissue and replace damaged/apoptotic cells by in-vivo differentiation. METHODS: Mortality, aortic diameter expansion, cell localization, cell differentiation, and inflammation of the dissected aorta were evaluated in type B-AAD model mice intravenously injected with human-Muse cells, -elastin-knockdown (KD)-Muse cells, -human leukocyte antigen-G (HLA-G)-KD-Muse cells, or MSCs, all without immunosuppressant. RESULTS: Here, we show the Muse (50,000 cells) group has a lower incidence of aortic rupture and mortality of AAD compared with the MSC-50K (50,000 human-MSCs) and vehicle groups. Spectrum computed tomography in-vivo dynamics and 3-dimensional histologic analyses demonstrate that Muse cells more effectively home to the AAD tissue and survive for 8 weeks in the Muse group than in the MSC-750K (750,000 human-MSCs containing 50,000 Muse cells) group. Homing of Muse cells is impeded in the HLA-G-KD-Muse (50,000 cells) group. Differentiation of homed Muse cells into CD31(+) and alpha-smooth muscle actin (+) cells, production and reorganization of elastic fibers in the AAD tissue, and suppression of diameter expansion are greater in the Muse group than in the MSC-750K and elastin-KD-Muse (50,000 cells) groups. CONCLUSIONS: Intravenously administered Muse cells reconstruct the dissected aorta and improve mortality and diameter enlargement rates. Moreover, small doses of purified Muse cells are more effective than large doses of MSCs. HLA-G is suggested to contribute to the successful survival and homing of Muse cells.

Acute aortic dissection (AAD) is a serious disease in which the largest artery in the body, called the aorta, enlarges and ruptures. Surgery is often required to prevent death. Cells called Muse cells have been injected into people during clinical trials to treat other diseases. In this study, we injected Muse cells into mice with dissected aorta. The cells accumulated in damaged parts of the aorta and strengthened the structure of the aorta, reducing the number of mice that died. If further research shows this treatment works in humans, this could enable AAD to be treated without surgery and potentially improve the treatment and survival of people with AAD.

Morphological Changes in the Infrapatellar Fat Pad During Walking Detected by Dynamic Ultrasound in Healthy Volunteers.

Aim This study aimed to verify specific morphological changes in the infrapatellar fat pad (IFP) during walking in healthy young participants. Methods A total of 17 healthy young participants (mean age, 22.8 ± 0.9 years) were recruited in this cross-sectional study. The IFP was evaluated using ultrasonography in three conditions: supine, standing, and walking. The IFP value was described as the thickness of the distal section of the IFP. Additionally, in the walking condition, the IFP was captured in video mode on ultrasonography, and its dynamics were recorded. The waveform of the IFP was produced using the sequence of the IFP thickness on each image. The morphological change of IFP (ΔIFP) was calculated in the IFP waveform and was shown as the difference in IFP thickness between the maximum and minimum at the beginning of the early stance phase. Moreover, kinematics and kinetic data were evaluated using a three-dimensional motion system, and the knee flexion angle (KFA) and knee flexion moment (KFM) were obtained. Results The thickness of the IFP during walking was significantly greater than that during the supine and standing conditions (p < 0.001 for both). The IFP waveform during walking showed a gradual increase during the stance phase and a decrease during the swing phase of the gait cycle. ΔIFP was 1.35 ± 0.42 mm and significantly correlated with the KFM (r = 0.59, p = 0.007). Conclusions Dynamic ultrasonography revealed a specific morphological change in the IFP during walking, which correlated with the KFM.

Laparoscopic resection of liver PEComa associated with Li­Fraumeni syndrome: A case report.

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with germline mutations in tumor suppressor gene TP53. Perivascular epithelioid cell tumors (PEComas) are a group of tumors by the World Health Organization Classification as mesenchymal tumors composed of histologically and immunohistochemically distinctive PECs. The present study reports a rare case of PEComa associated with LFS. A 32-year-old female patient was referred to Tokyo Metropolitan Tama Medical Center (Tokyo, Japan) in March 2022 for a detailed examination of a liver mass. The patient had received a diagnosis of LFS based on a history of sarcoma and germline variants of TP53 7 years previously. Magnetic resonance imaging revealed a ring-enhanced mass in the liver segment 8 (S8). This was observed in the arterial phase, followed by washout of contrast media in the venous phase. Owing to the possibility of malignancy (such as metastatic liver tumor or hepatocellular carcinoma), the patient was referred for diagnostic surgery. In August 2022, a laparoscopic partial hepatectomy of S8 was performed without complications and she was discharged on postoperative day 7. The pathological findings led to the diagnosis of PEComa. The patient is currently under follow-up at 1 year and 4 months postoperative. Laparoscopic hepatectomy was useful as a diagnostic treatment because it was relatively non-invasive. Mutations in TP53 are involved in the development of PEComa. Further cases and studies are required to clarify the relationship between LFS and PEComa.

The improvised expert: Staging authority at an OECD Nuclear Energy Agency workshop in Fukushima.

In recent years, concerns about a crisis of expert authority have been expressed across the globe. Japan is no exception to this trend. Scandals surrounding the (mis)management of the 2011 Fukushima Daiichi nuclear power plant disaster severely damaged public confidence in state institutions, posing an additional challenge for those engaged in radiological protection. This article examines how claims to expert authority are made in these conditions of low public trust. To this end, I offer an ethnographic account of the OECD Nuclear Energy Agency's (NEA) Workshop on Post-Accident Food Safety Science-an event staged at the request of the Japanese Cabinet Office with the aim of inspiring confidence in Fukushima produce. I analyse the practices through which the organizers craft a credible public persona using the idiom of dramaturgical improvisation; drawing attention to the 'performed resourcefulness' with which they adapted extant institutional scripts in response to a discerned crisis of public reason. Concretely, improvisation invites us to consider how and why nuclear policy actors have sought to demarcate two variants of the deficit model: the (psychological) discourse of 'radiophobia' and the (economic) discourse of 'reputational damage'. Where prior scholarship has identified the continuities between the two discourses, an attention to this boundary work reveals the dramaturgical advantages of 'reputational damage' over 'radiophobia' in contesting critics' claims to the mantle of victimhood, securing international support, and producing the expert's body as a site of evidence.

Evaluation under loading detects medial meniscus extrusion in patients with reconstructed anterior cruciate ligament and restricted knee extension.

PURPOSE: Some patients who undergo anterior cruciate ligament (ACL) reconstruction experience abnormal mechanical stress in the meniscus. Medial meniscal extrusion (MME) is reflected in the pathological condition of the meniscus, which expands owing to repetitive mechanical stress. Thus, the effect of the reconstructed ACL on increasing MME under weight-bearing conditions remains unclear. This study investigated the effect of ACL reconstruction on meniscal extrusion under non-weight-bearing and weight-bearing conditions. METHODS: Seventeen patients who underwent unilateral ACL reconstruction (ACL group) and 20 age-matched healthy volunteers (control group) were enrolled. Ultrasonography was performed in the supine, standing, and walking positions in preoperative and postoperative ACL patients. MME during walking was evaluated based on the dynamic behavior of extrusion, and kinetic and kinematic data were synchronously obtained. Moreover, the ACL group underwent magnetic resonance imaging (MRI) evaluation at two points: preoperatively and 12 months postoperatively, and the ultrasound findings were compared. RESULTS: MME in the supine position measured using both ultrasonography and MRI was not significantly different preoperatively and postoperatively in the ACL group. However, postoperative MME and dynamic behavior of extrusion under standing and walking conditions were significantly higher than those in the preoperative state (dynamic behavior: 0.9 ± 0.4 mm preoperatively, 1.2 ± 0.4 mm postoperatively). Moreover, the deficits in knee extension during walking persisted postoperatively and were significantly higher than those in the control group. CONCLUSION: MME in patients with ACL reconstruction including meniscus repair was different under mechanical stress compared to the non-weight bearing condition.

Individuals with asymptomatic hallux valgus exhibit altered foot kinematics during gait regardless of their foot posture.

BACKGROUND: A flatfoot has been believed to be closely associated with the development of hallux valgus; however, the association is still controversial. Abnormal foot kinematics has been identified as a possible risk factor for the development of hallux valgus, but it remains unclear whether foot posture contributes to abnormal foot kinematics. This is the first study to investigate the differences in foot kinematics during gait between individuals with and without hallux valgus, while controlling for foot posture. METHODS: Twenty-five females with hallux valgus and 25 healthy females aged 18 to 22 were recruited. Foot posture was measured using normalized navicular height truncated and the leg-heel angle. Foot kinematic and kinetic data during gait were recorded by a three-dimensional motion capture system. To investigate the characteristics of foot kinematics in individuals with hallux valgus while controlling for foot posture, we used a propensity score matching method. The matching was obtained by using the 1:1 nearest-neighbor procedure and a caliper width of 0.2. FINDINGS: Twelve pairs were matched. Individuals with hallux valgus had significantly increased midfoot dorsiflexion from 56% to 80% during stance phase, rearfoot eversion from 53% to 71%, and forefoot abduction from 5% to 29% compared with control. INTERPRETATION: Individuals with hallux valgus have a flexible foot that cannot suppress the dynamic deformation of the rearfoot and midfoot during gait. To suppress the development of hallux valgus, interventions that aim to prevent dynamic deformations of the rearfoot and midfoot during gait may be necessary, regardless of their static foot posture.

Prognostic utility of circulating tumor DNA methylation analysis in stage IV colorectal cancer.

BACKGROUND AND OBJECTIVES: Our aim in this study was to investigate the usefulness of circulating tumor (ct) DNA methylation analysis for predicting long-term outcomes after resection in Stage IV colorectal cancer (CRC). METHODS: Methylation analyses were performed on 95 plasma samples from patients with CRC who underwent surgery. The methylation status (relative methylation value: RMV) of CpG within the promoter region of three genes (CHFR, SOX11, and CDO1) was assessed to quantitative methylation-specific PCR (qMSP) analysis. RESULTS: In the patients who had undergone resection of the primary tumor and metastatic organs with curative intent, the CHFR-RMV high group had significantly worse recurrence-free survival (RFS) compared with the CHFR-RMV low group (p = 0.001). Multivariate analysis revealed that CHFR-RMV was a significant independent prognostic factor (hazard ratio = 2.63 (1.29-5.36); p = 0.008). In the patients who had undergone resection of the primary tumor with metastatic organs with curative intent after neoadjuvant systemic chemotherapy, the SOX11-RMV high group had significantly worse RFS compared with the SOX11-RMV low group (p = 0.004). CONCLUSIONS: The current study showed the usefulness of ctDNA methylation analysis for predicting the possibility of curative resection and long-term outcomes after resection in Stage IV CRC. A future prospective study is needed to obtain more conclusive results.

Morphologic changes in the posterior glenoid rim is independently associated with rotator cuff impingement in baseball players.

Background: The morphological changes in the posterior glenoid rim are unknown in relation to the area of rotator cuff tendons pinched within the glenohumeral joint in the throwing shoulders of baseball players. Therefore, this study aimed to clarify whether these changes are associated with the area of impingement in baseball players. Methods: Overall, 25 asymptomatic male college baseball players (average age19.8 years, 11.6 years of competing, and 50 shoulders) participated in this study. The area of impingement (AOI, mm2) and posterior glenohumeral distance (PGHD, mm) were measured using magnetic resonance imaging to quantitatively assess the impingement area of the rotator cuff tendon within the glenohumeral joint and the morphologic change in the posterior glenoid rim. These magnetic resonance imaging assessments were measured at 90° shoulder abduction with 90° and 100° external rotation. Multiple linear regression analysis was performed to determine whether AOI is predicted by PGHD. Findings: Multiple linear regression analysis showed that the PGHD was a predictor of the AOI at external rotation 90° (ß-coefficient = 0.738, R2 = 0.77, P < 0.001) and external rotation 100° position (ß-coefficient = 0.879, R2 = 0.76, P < 0.001). Interpretation: This study found that the area of impingement was associated with posterior glenohumeral distance. Therefore, these findings may indicate that complex shoulder joint morphologic changes result in a disabled throwing shoulder.

Oral stimulation with glucose and fructose, but not sucrose, accelerates gastric emptying in humans.

Postprandial regulation of the gastric emptying (GE) rate plays an important role in food intake. Although oral sweetening with glucose may accelerate GE, the effects of different sweetness intensities of glucose (10% and 20%, w/v) and other energy sweeteners (e.g. fructose and sucrose) remain uncertain. The purpose of this study was to determine the effects of different glucose concentrations (Experiment 1) and different sugars with the same sweet taste intensity (Experiment 2) on postprandial GE. In both experiments, after ingesting a 200 kcal carbohydrate solution containing 50 g of maltodextrin, participants repeatedly sipped, but did not swallow, one of three (water, 10% and 20%, w/v glucose) or four (water and equally sweet 20%, w/v glucose, 12%, w/v fructose, and 14%, w/v sucrose) solutions for 1 min every 5 min over a 30 min period. GE was evaluated by measuring the temporal change in the cross-sectional area of the gastric antrum using ultrasound. In Experiment 1, oral stimulation with 20% (w/v) glucose resulted in greater GE than the control stimulus (i.e. water), but the effect of stimulation with 10% (w/v) glucose on GE was not different from that of the control stimulus. In Experiment 2, stimulation with 20% (w/v) glucose or 12% (w/v) fructose resulted in greater GE than the control stimulus. However, the effect of stimulation with 14% (w/v) sucrose on GE did not differ from that of the control stimulus. Consequently, oral stimulation with glucose or fructose solutions of moderate to high sweetness following a meal facilitates postprandial GE.

Use of 3D-CT-derived psoas major muscle volume in defining sarcopenia in colorectal cancer.

BACKGROUND: Sarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC. METHODS: The subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups. RESULTS: The S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60). CONCLUSIONS: The PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method.

Exploring the use of telepractice Dohsa-hou to adults with intellectual disabilities.

This study presents the application of an authentic Japanese bodywork approach Dohsa-hou to adults with intellectual disabilities who live in a care facility. Amid the COVID-19 pandemic, such people remained disconnected from their families and friends, for which reason many of them experience anxiety, stress and inability to enjoy leisure activities. Given the lockdown circumstances, we decided to use for the first time in the field telepractice to provide Dohsa-hou. The results showed that participants experienced a gradual positive mood change and also expressed a desire to continue the sessions. Considering this, although further research is still needed, we assume that telepractice Dohsa-hou might be a viable substitute for the face-to-face sessions.

Effects of age and flight experience on prefrontal cortex activity in airline pilots: An fNIRS study.

It is essential for airlines to have a deep understanding of the cognitive impact of aging among pilots. The current literature on executive function indicates that compensatory mechanisms in the brain may counteract age-related cognitive decline, at least up to certain task load levels. However, few studies have been administered to evaluate changes in aircrew competence as they age. The present study focuses on dorsolateral prefrontal cortex (DLPFC) activity as it is implicated in cognitive performance and working memory, which are associated with skill proficiency. We measured the DLPFC activity for airline pilots, including trainees, during maneuvering using a flight simulator. Our preliminary results indicated that only expert (aged) pilots demonstrated higher activity of the left DLPFC than the right one. However, for youth trainees, not only was the error rate high while using the flight simulator, but the activity of the DLFPC was also lower than that of the expert pilots, and there was no statistically significant difference between the left and right DLPFC. Although these findings partially differ from those reported in previous studies on age-related changes, it is evident that training as an airline pilot for over 20 years may affect such results. We believe that this noninvasive approach to objective quantification of skill will facilitate the development of effective assessment competence in aging.

Temporary meniscus extrusion is caused by cumulative stress from uphill and downhill tasks in healthy volunteers.

Purpose: Excessive mechanical stress accumulates and causes knee injury. Meniscal extrusion is a key factor in detecting the reaction to cumulative mechanical stress. The accumulation of stress strongly depends on environmental conditions such as flat ground or uphill/downhill, and accumulates in knee compartments; only a few studies have reported the effects of different environments on lateral and medial meniscus extrusion. This study aimed to investigate the effects of cumulative uphill/downhill stress on the meniscal extrusion in each compartment. Methods: A total of 30 healthy volunteers with 30 affected knees were involved in this cohort study (mean age, 22.0 ± 1.1 years; men, n = 14). The participants were divided into flat-walking, uphill/downhill-walking, and uphill/downhill-jogging groups and their numbers of steps taken were recorded during the effort. Moreover, medial and lateral meniscal extrusions during walking were evaluated using ultrasound three times, before and after efforts (T1) and (T2), and one day after efforts (T3), respectively. Results: In the flat-walking group, no significant differences were observed between the follow-up periods. Conversely, in the uphill/downhill-walking and jogging groups, the medial meniscus extrusion at T2 was significantly higher than that at T1. Conversely, the medial meniscus extrusion at T3 was significantly lower than that at T2. By contrast, the lateral meniscus did not show any difference between the follow-up periods in any group. Conclusion: Temporary extrusion of the meniscus occurred after uphill/downhill tasks in healthy volunteers, and its reaction was observed only in the medial meniscus.

Two Surgical Cases of Colorectal Cancer in Patients With Immunoglobulin G4-Related Disease.

Immunoglobulin G4-related disease (IgG4RD) is a relatively new disease concept that is most common in Asia. It is a systemic chronic lymphoproliferative disease that is diagnosed by mass formation or thickened lesion, a high serum IgG4 level (≥135 mg/dL), and confirmation of lymphocytes and plasma cells by histopathological examination. The precise mechanism of this disease remains elusive; however, distinguishing IgG4RD from malignancy proves challenging due to its manifestation of swollen lymph nodes and retroperitoneal thickening and fibrosis. Malignancy is also 3.5 times more likely in cases with IgG4RD. In this study, we report two cases of colorectal cancer in patients with IgG4RD who underwent surgery. In both cases, excising the tumor from the retroperitoneal posed a challenge, and swollen lymph nodes were observed without evidence of cancer metastasis. We believe that these are very informative cases, and we report the cases with a literature review of IgG4RD.

Effect of lateral wedge length on knee adduction moment reduction mechanics during gait.

Lateral wedge insole (LWI) wear is a well-known conservative treatment for patients with knee osteoarthritis and is expected to decrease knee joint loading. Although the effect of LWI length on knee adduction moment (KAM) has been investigated, the biomechanical mechanism has not been fully investigated. Twelve healthy young subjects walked in the laboratory with and without 2 different lengths of LWIs. Three-dimensional motion analysis was performed to calculate the first and second peaks and impulses of the KAM during the stance phase. In addition, the knee-ground reaction force lever arm (KLA) and center of pressure (COP), ankle eversion moment, and ankle eversion angle were calculated. The first peak of KAM was lower, COP was displaced outward, and KLA was shorter with both LWIs attached. On the other hand, the second peak of KAM was lower with longer LWIs, COP was displaced outward, and KLA was shorter. The KAM impulse was significantly smaller in the condition with longer LWI than in the other conditions with smaller ankle eversion motion; longer LWI induced COP to the lateral side through the stance phase and kept KLA short, thus reducing the KAM impulse.

Medial meniscus extrusion during gait is associated with decrease in knee rotation in early-stage knee osteoarthritis.

BACKGROUND: In patients with medial knee osteoarthritis (OA), medial meniscus extrusion during gait is aggravated by mechanical stress, such as knee adduction moment (KAM). Conversely, the decrease in the range of knee rotation during stance phase is also one of the important issues in early knee OA, whereas the correlation between medial meniscus extrusion and knee rotation during gait are unclear. RESEARCH QUESTION: To investigate the correlation between increase in medial meniscus extrusion and range of knee rotation during gait in patients with early- and late-stage of knee OA. METHODS: Forty patients with medial knee OA were enrolled and divided into early- and late-OA group by Kellgren-Lawrence grading scale. During gait tasks, the extent of medial meniscus extrusion was measured using ultrasonography and kinetic/kinematic data were measured using three-dimensional motion analysis system. The correlation between medial meniscus extrusion and the range of knee rotation or KAM were evaluated in the overall, early-, and late- OA groups. RESULTS: A significant negative correlation was observed between an increase in medial meniscus extrusion and range of knee rotation angle in early-OA group only. However, an increase in medial meniscus extrusion significantly correlated with the second KAM peak in the overall and early-OA groups. SIGNIFICANCE: The decrease in range of knee rotation during stance phase may be associated with the increase in medial meniscus extrusion during gait in patients with early knee OA.

Usefulness of thermography for differentiating Wallenberg's syndrome from noncentral vertigo in the acute phase.

OBJECTIVES: Wallenberg's syndrome (WS) is caused by a stroke in the lateral medulla and can present with various symptoms. One of the main symptoms is vertigo, which can be misdiagnosed as noncentral vertigo (NCV). Approximately 90% of the patients with acute WS have a lateral difference in body surface temperature (BST) due to autonomic pathway disturbances from infarction. Additionally, thermography can aid in WS diagnosis; however, whether BST differences occur in patients with acute NCV is unclear. METHODS: This study used thermography to measure the BST of patients with NCV and acute WS to determine the effectiveness of BST to differentiate between the conditions. Forty-eight consecutive patients diagnosed with NCV whose BST was measured using thermography during a hospital visit or admission were enrolled. The left and right BST of four sites (face, trunk, and upper and lower limbs) were measured and compared with obtained BST of nine patients with WS. RESULTS: Twenty-two patients had lateral differences in BST ≥ 0.5°C, three with ≥1.5°C, and none with ≥2.5°C. Only one patient with NCV had lateral differences in BST at two or more ipsilateral sites. When WS differentiated from NCV, a left-right difference ≥0.5°C in two or more ipsilateral sites had a sensitivity of 89% and specificity of 98%, and ≥1.0°C had a sensitivity of 78% and specificity of 98%. DISCUSSION: Acute WS can be differentiated from NCV through BST and the number of sites with lateral differences via thermography, even in rooms where conditions are unregulated.

Effect of lateral wedge insole on medial meniscus extrusion and its association with knee osteoarthritis progression.

BACKGROUND: Medial meniscus extrusion (MME) is associated with knee osteoarthritis (OA) progression because of increased loading stress in the medial compartment of the knee. Using a lateral wedge insole (LWI) decreases loading stress and immediately reduces MME. OBJECTIVE: To investigate whether the wearing duration of LWI affects the midterm response to MME and is associated with knee OA progression. STUDY DESIGN: Cohort study. METHODS: Twenty-three patients with knee OA who were conservatively treated with LWI were classified according to the duration of the LWI wear per day: less than 5 h (short-duration group) or over 5 h (long-duration group). MME was evaluated in the single-leg standing position by ultrasound. Knee OA progression and limb alignment were evaluated radiographically. These evaluations were performed thrice: at the initial office visit as a baseline without LWI (time 0), with LWI (LWI-time 0), and 1 year after intervention with LWI (LWI-1 year). RESULTS: In both groups, the MMEs at LWI time 0 were significantly decreased compared with those at time 0. In the long-duration group, this reduction in MME was maintained 1 year after the intervention compared with time 0 (time 0: 3.9 ± 0.9, LWI-1 year: 2.6 ± 1.1), but this improvement was not observed in the short-duration group (time 0: 3.8 ± 1.7, LWI-1 year: 3.6 ± 1.7). In addition, three of four patients demonstrated OA progression, and varus alignment had significantly progressed compared with that at time 0 in the short-duration group. However, the long-duration group showed OA progression only in one patient and maintained limb alignment. CONCLUSIONS: The duration of wearing LWI affects the midterm reduction of MME and knee OA progression while maintaining limb alignment.

Influence of genetic polymorphisms in vascular endothelial-related genes on the clinical outcome of axitinib in patients with metastatic renal cell carcinoma.

OBJECTIVE: Axitinib is an oral multi-target tyrosine kinase inhibitor used for the treatment of renal cell carcinoma (RCC). Because of the severe adverse events (AEs) associated with axitinib, patients often need dose reductions or discontinue its use, highlighting the need for effective biomarkers to assess efficacy and/or AEs. The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in genes involved in the pharmacodynamic action of axitinib and clinical prognosis and AEs in metastatic RCC (mRCC) patients. METHODS: This study included 80 mRCC patients treated with first-, second-, or third-line axitinib (5 mg orally twice daily). Clinical parameters and genetic polymorphisms were examined in 75 cases (53 males and 22 females). We assessed three SNPs in each of three candidate genes namely, angiotensin-converting enzyme (ACE), nitric oxide synthase 3 (NOS3), and angiotensin II receptor type 1 (AT1R), all of which are involved in axitinib effects on vascular endothelial function. RESULTS: Axitinib-treated patients carrying the ACE deletion allele suffered more frequently from hand-foot syndrome and a deterioration in kidney function (p = .045 and p = 0.005, respectively) whereas those carrying the NOS3 G allele suffered more frequently from proteinuria and multiple AEs (p = .025 and p = 0.036, respectively). CONCLUSIONS: Our study found that the ACE deletion allele and the NOS3 G allele are associated with increased AEs.