Nirmatrelvir Resistance in an Immunocompromised Patient with Persistent Coronavirus Disease 2019.

Although the coronavirus disease 2019 (COVID-19) pandemic is coming to an end, it still poses a threat to the immunocompromised and others with underlying diseases. Especially in cases of persistent COVID-19, new mutations conferring resistance to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapies have considerable clinical implications. We present a patient who independently acquired a T21I mutation in the 3CL protease after nirmatrelvir exposure. The T21I mutation in the 3CL protease is one of the most frequent mutations responsible for nirmatrelvir resistance. However, limited reports exist on actual cases of SARS-CoV-2 with T21I and other mutations in the 3CL protease. The patient, a 55 year-old male, had COVID-19 during chemotherapy for multiple myeloma. He was treated with nirmatrelvir early in the course of the disease but relapsed, and SARS-CoV-2 with a T21I mutation in the 3CL protease was detected in nasopharyngeal swab fluid. The patient had temporary respiratory failure but later recovered well. During treatment with remdesivir and dexamethasone, viruses with the T21I mutation in the 3CL protease showed a decreasing trend during disease progression while increasing during improvement. The impact of drug-resistant SARS-CoV-2 on the clinical course, including its severity, remains unknown. Our study is important for examining the clinical impact of nirmatrelvir resistance in COVID-19.

Hybrid representation-enhanced sampling for Bayesian active learning in musculoskeletal segmentation of lower extremities.

PURPOSE: Manual annotations for training deep learning models in auto-segmentation are time-intensive. This study introduces a hybrid representation-enhanced sampling strategy that integrates both density and diversity criteria within an uncertainty-based Bayesian active learning (BAL) framework to reduce annotation efforts by selecting the most informative training samples. METHODS: The experiments are performed on two lower extremity datasets of MRI and CT images, focusing on the segmentation of the femur, pelvis, sacrum, quadriceps femoris, hamstrings, adductors, sartorius, and iliopsoas, utilizing a U-net-based BAL framework. Our method selects uncertain samples with high density and diversity for manual revision, optimizing for maximal similarity to unlabeled instances and minimal similarity to existing training data. We assess the accuracy and efficiency using dice and a proposed metric called reduced annotation cost (RAC), respectively. We further evaluate the impact of various acquisition rules on BAL performance and design an ablation study for effectiveness estimation. RESULTS: In MRI and CT datasets, our method was superior or comparable to existing ones, achieving a 0.8% dice and 1.0% RAC increase in CT (statistically significant), and a 0.8% dice and 1.1% RAC increase in MRI (not statistically significant) in volume-wise acquisition. Our ablation study indicates that combining density and diversity criteria enhances the efficiency of BAL in musculoskeletal segmentation compared to using either criterion alone. CONCLUSION: Our sampling method is proven efficient in reducing annotation costs in image segmentation tasks. The combination of the proposed method and our BAL framework provides a semi-automatic way for efficient annotation of medical image datasets.

SARS-CoV-2 RT-PCR as a universal screening on planned admission in asymptomatic patients.

Universal screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on admission is reportedly beneficial in preventing nosocomial infections. However, some issues remain, including low positivity rate, cost, and time required for testing. We describe SARS-CoV-2 reverse transcription polymerase chain reaction (PCR) for universal screening in asymptomatic patients on planned admissions. In total, 14,574 patients were included between October 12, 2020, and June 23, 2022. The PCR-positive rate for the period was 0.44 % (64/14,574). The PCR positivity for the epidemic period by strain was 0.28 % (95 % confidence interval [CI] 0.12-0.56 %), 0.16 % (95 % CI 0.05-0.37 %), 0.21 % (95 % CI 0.09-0.41 %), and 0.9 % (95 % CI 0.65-1.2 %) for the wild-type strain, Alpha, Delta, and Omicron variants, respectively. The proportion of Ct values < 30 was higher in the first half of the epidemic (first vs. second, 29.4 % [95 % CI 16.9-44.8 %] vs. 16.7 % [95 % CI 6.0-28.5 %]), whereas that of Ct values ≥ 35 increased significantly in the second half (first vs. second, 32.4 % [95 % CI 19.3-47.8 %] vs. 70.0 % [95 % CI 53.5-83.4 %]). Of all positives, 50 % (32/64) had a coronavirus disease (COVID-19) history before PCR screening, with a median of 28 days (10-105) from COVID-19 onset or positive to PCR screening. PCR screening may help detect positives with high viral loads early in the epidemic for each mutant strain, with an increasing proportion of positives with low viral loads later in the epidemic. PCR testing may be unnecessary for recently diagnosed cases and patients in whom reinfection is unlikely.

Red dichromatic imaging improves visibility of bleeding during gastric endoscopic submucosal dissection.

Bleeding frequently occurs during gastric endoscopic submucosal dissection (ESD) and bleeding points are sometimes difficult to detect. Red dichromatic imaging (RDI) was recently developed to improve the visibility of bleeding. Our study aimed at examining the efficacy of RDI in improving the visibility of bleeding during gastric ESD. We retrospectively evaluated the visibility score and color difference of bleeding spot during gastric ESD during September 2020-January 2021. The visibility score was evaluated as four numeric values by operators, and the color difference between the bleeding spot and surroundings was evaluated using RDI and white light imaging (WLI). A further analysis to evaluate bleeding characteristics was performed to evaluate the possible beneficial effects of RDI. Twenty patients with a total of 85 bleedings were analyzed. The mean visibility score in RDI was significantly higher than that in WLI (3.69 ± 0.60 vs 3.20 ± 0.84, p < 0.01). The color difference with RDI was also significantly higher than that with WLI (19.51 ± 15.18 vs 14.80 ± 7.41, p < 0.01). Furthermore, in the bleedings with a higher visibility score in RDI, the color difference in RDI was significantly higher than that in WLI (23.99 ± 19.29 vs 14.33 ± 7.08, p < 0.01). The multivariate analysis of visibility scores revealed that submergence of bleeding points was independently associated with the superiority of RDI (odds ratio 10.35, 95% confidence interval: 2.76-38.81, p < 0.01). Our study demonstrates that RDI can improve the visibility of bleeding during gastric ESD.

Ultrasonographic echo intensity in the medial femoral cartilage is enhanced prior to cartilage thinning in women with early mild knee osteoarthritis.

PURPOSE: We aimed to determine whether altered cartilage echo intensity is associated with knee osteoarthritis (OA) severity and whether the alteration occurs before thinning of the femoral cartilage in knee OA. METHODS: The medial femoral cartilage thickness and echo intensity of 118 women aged ≥ 50 years were assessed using an ultrasound imaging device. Based on the Kellgren-Lawrence (KL) grade and knee symptoms, participants were classified into five groups: control (asymptomatic grades 0-1), early OA (symptomatic grade 1), grade 2, grade 3, and grade 4. Analysis of covariance, with adjusted age and height, and the Sidak post hoc test were used to assess the differences in cartilage thickness and echo intensity in knees with varying OA severity. RESULTS: The echo intensity on longitudinal images, equivalent to the tibiofemoral weight-bearing surface, was significantly higher in the grade 2 group than that in the control group (p = 0.049). However, no significant difference was noted in cartilage thickness (n.s.). In the grades 3 and 4 groups, cartilage thickness became thinner as OA progressed (p < 0.001 and p < 0.001, respectively). However, the cartilage echo intensity was not significantly enhanced compared with that of the grade 2 group (n.s.). There were no significant differences in the cartilage thickness and echo intensity between the early OA and control groups on the longitudinal images (n.s.). CONCLUSIONS: The echo intensity of the medial femoral cartilage was high in patients with KL grade 2, without decreased thickness. Our findings suggested that higher echo intensity is a feature of early cartilage degeneration in mild knee OA. Further studies are needed to establish this feature as a useful screening parameter of early cartilage degeneration in knee OA. LEVEL OF EVIDENCE: Level III.

Predictors of response to anamorelin in gastrointestinal cancer patients with cachexia: a retrospective study.

PURPOSE: Anamorelin, a ghrelin receptor agonist, has recently been approved for gastric, pancreatic, and colorectal cancer patients with cachexia in Japan. However, only few studies have investigated the predictors of response to anamorelin in clinical settings. Thus, our study aimed to investigate the predictors of the response, in addition to its efficacy and safety. METHODS: The clinical outcomes of 20 patients were evaluated during administration. They were divided into two groups based on lean body mass, responders and non-responders, and their clinical characteristics were compared. RESULTS: The mean ± standard error (SE) variations at 12 weeks in lean body mass and handgrip strength were 2.63 ± 0.79 kg and - 1.53 ± 1.20 kg, respectively. The mean ± SE variations at 8 weeks in fasting blood glucose and hemoglobin A1c were 32.88 ± 13.77 mg/dL and 0.90 ± 0.18%, respectively. Total protein, albumin, transferrin, and prognostic nutritional index at baseline were significantly higher in responders (n = 8) than in non-responders (n = 12), whereas the neutrophil/lymphocyte and C-reactive protein/albumin ratios at baseline were significantly higher in non-responders than in responders. CONCLUSION: The study confirmed the efficacy and safety of anamorelin and identified nutritional or systemic inflammatory markers as predictors of anamorelin response in advanced gastrointestinal cancer patients.

Interstitial Lung Disease Associated with Agaricus blazei Murill in a Patient with Pancreatic Ductal Adenocarcinoma Receiving Gemcitabine-Based Therapy.

A male in his sixties with locally advanced pancreatic ductal adenocarcinoma (PDAC) was administered gemcitabine plus nab-paclitaxel therapy. Computed tomography (CT) scans after five courses revealed nonspecific interstitial pneumonitis in addition to PDAC aggravation. No evidence of respiratory infection was detected, and his condition was stable and asymptomatic at diagnosis. Sputum test and interferon-gamma release assay revealed no evidence of tuberculosis. Through careful history taking, the patient was found to be taking dietary supplementation with Agaricus blazei Murill extract for approximately 1 month. Drug-induced lymphocyte stimulation tests for gemcitabine and nab-paclitaxel were negative, whereas those for Agaricus blazei Murill were positive. CT scans after withdrawal showed improved pneumonitis. These findings suggest a possibility that the dietary supplementation may lead to drug-induced interstitial lung disease (ILD). This patient indicates that pertinent diagnostic interviews are essential for the identification of drug-induced ILD.

Association of Physical Activity and Nutritional Intake with Muscle Quantity and Quality Changes in Acute Stroke Patients.

OBJECTIVES: To evaluate longitudinally the muscle properties of acute stroke patients and examine the association between physical activity and nutritional intake. MATERIALS AND METHODS: This study enrolled 21 stroke patients (72.7±10.4 years). Muscle quantity (fat-free mass, appendicular skeletal muscle mass) and quality (extracellular water/intracellular water ratio, phase angle) were assessed using a bioelectrical impedance device at baseline (within three days) and two weeks after stroke onset. Physical activity and sedentary were calculated from the accelerometer data. Total energy and protein intake were calculated from the dietary surveys as nutritional intake. The association of physical activity, sedentary, and nutritional intake with the rate of changes in muscle properties was examined. RESULTS: The fat-free mass significantly decreased (from 43.4±8.0 to 42.2±7.6 kg), and the skeletal muscle was unchanged (from 17.8±4.2 to 17.7±4.0 kg) after two weeks. The extracellular water/intracellular water ratio significantly increased (from 0.63±0.02 to 0.65±0.03) and the phase angle significantly decreased (from 5.1±0.6 to 4.9±0.8°), suggesting that the muscle quality have declined. Correlation analysis showed that the extracellular water/intracellular water ratio was significantly associated with physical activity [metabolic equivalents (ρ=-0.61)] and sedentary (ρ=0.67) and that the phase angle was significantly associated with physical activity [metabolic equivalents (ρ=0.69)], sedentary (ρ=-0.68), and nutritional intake [total energy (r=0.45), protein (r=0.45)]. CONCLUSIONS: The fat-free mass and muscle quality (extracellular water/intracellular water ratio and phase angle) declined two weeks after stroke. Physical activity and nutritional intake were lower in patients with decreased muscle quality, suggesting the importance of exercise and nutrition in the acute phase.

Microbiological analysis of patients with first and recurrent episodes of acute cholangitis in a middle-sized hospital: A single-center retrospective study in rural North Kyoto, Japan.

BACKGROUND: Knowledge of the bacterial spectrum involved in acute cholangitis is essential for adequate empiric antibiotic treatment. There is a lack of published data comparative data between patients with first and recurrent episodes of acute cholangitis. This study aimed to analyze the microbial spectrum in patients with first and second episodes of acute cholangitis. METHODS: We retrospectively assessed 251 patients with first episodes of acute cholangitis between January 2014 to September 2020. RESULTS: At the first episode of acute cholangitis, the predominant strains belonged to Escherichia coli (17.9%), followed by Klebsiella spp. (15.5%), Enterobacter spp. (6.4%), and Enterococcus spp. (5.6%). During follow-up, acute cholangitis recurred in 109 patients; at the second episode, the predominant strains belonged to Enterococcus spp. (35.8%), followed by Klebsiella spp. (27.5%), Enterobacter spp. (22.9%), and Escherichia coli (15.6%). Enterococcus spp. were the most common pathogen in patients with second episode of acute cholangitis, regardless of whether the cholangitis was caused by a malignant tumor or a benign disease. CONCLUSIONS: Unlike in patients with a first episode of acute cholangitis, clinicians should consider empirical treatment with anti-enterococcal antibiotics in patients with recurrent episodes of acute cholangitis.

Depletion of Psoas Muscle Mass after Systemic Chemotherapy Is Associated with Poor Prognosis in Patients with Unresectable Pancreatic Cancer.

The impact of the psoas muscle mass index (PMI) on survival is still poorly understood in unresectable pancreatic cancer. Thus, we aimed to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The data of 100 patients were analyzed, and they were divided into two groups according to the median PMI in each sex. Subsequently, 72 patients undergoing computed tomography (CT) within 30-100 days from CT at diagnosis were evaluated in terms of PMI change rate, and divided into two groups based on the median. We evaluated the clinical characteristics and outcomes in terms of the PMI at diagnosis or its decrease during chemotherapy. The median PMI was 5.00 in males, and 3.66 in females. The median overall survival (OS) was 278.0 days in the high-PMI group and 221.0 days in the low-PMI group (p = 0.329). The median PMI change rate was -2.4%. The median OS was 347.0 days in the group without PMI decrease and 172.0 days in the group with PMI decrease (p = 0.001). We determined that a pivotal prognostic factor was not the PMI at diagnosis, but rather PMI decrease during chemotherapy in unresectable pancreatic cancer.

Unusual abscess formation in colon cancer with mucinous components.

Colon cancer with mucinous components was accompanied by bacterial infection and abscess formation.

Physical Activity Mediates the Relationship between Gait Function and Fall Incidence after Total Knee Arthroplasty.

The present study aims to examine (1) the preoperative factors that can predict postoperative falls, (2) whether postoperative physical activity (PA) mediates the relationship between fall incidence and gait function, and (3) whether postoperative PA levels are associated with fall risk in total knee arthroplasty (TKA) patients. Ninety-six patients (mean age: 72.0 ± 6.1 years) who were observed postoperatively for 6 months were selected. Timed up and go (TUG) was assessed as an indicator of gait function. Fall incidence and PA were investigated for 6 months post-TKA. The body mass index, history of preoperative falls, knee pain, knee extensor strength, range of motion in knee flexion, and modified gait efficacy scale were evaluated. Additionally, postoperative PA levels were categorized into three groups-low: <3,000, moderate: 3,000 to 4,000, and high: ≥4,000 steps/day. The relative fall incidence rate was calculated according to the total number of falls normalized for every 1,000 steps/day for 6 months postoperatively. Twenty-five (26.0%) of the 96 patients had at least one fall. The TUG, knee pain, and knee extensor strength were identified preoperatively as significant variables affecting postoperative falls. The mediated effects model revealed that postoperative fall incidence was predicted by preoperative TUG and postoperative PA. Postoperative PA was significantly associated with preoperative TUG. Moreover, both the preoperative TUG and postoperative PA were selected as significant variables for predicting fall incidence. Thus, postoperative PA mediates the relationship between gait function and fall incidence after TKA. Furthermore, the relative fall incidence rate associated with a low PA level was significantly higher than that associated with moderate and high PA levels. In conclusion, preoperative assessments of TUG performance, muscle strength, and knee pain were effective in predicting fall risk. Additionally, an increase in PA could contribute to reducing fall risk in TKA patients. Therefore, our results suggest that preoperative screening for fall predictors and managing postoperative PA could reduce the fall incidence in TKA patients.

Neutrophil to lymphocyte ratio predicts prognosis in unresectable pancreatic cancer.

Inflammation-based prognostic indicators have been developed to predict the prognosis in patients with pancreatic cancer. However, prognostic indices have not been established in patients with unresectable pancreatic cancer, including those without indication for chemotherapy at diagnosis. This study aimed to identify the predictors in all patients with unresectable pancreatic cancer. We retrospectively analyzed data of 119 patients with unresectable pancreatic cancer from June 2006 to September 2018. The following laboratory parameters were evaluated: the Glasgow Prognostic Score (GPS), modified GPS, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein albumin (CRP/Alb) ratio, and prognostic nutritional index (PNI). We performed time-dependent receiver operating characteristic analysis, overall survival (OS) analysis, and univariate and multivariate analyses to determine the prognostic factors in patients with unresectable pancreatic cancer. The cut-off value for NLR was determined to be 3.74. The 6-month OS rates in low and high NLR groups were 75.5% and 18.8% (P < 0.001). In the univariate analysis, advanced age (P = 0.003), metastatic pancreatic cancer (P = 0.037), no treatment (P < 0.001), worse Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (P < 0.001), high GPS (P < 0.001), high modified GPS (P < 0.001), high NLR (P < 0.001), high PLR (P = 0.002), high CRP/Alb ratio (P < 0.001), and low PNI (P < 0.001) were identified as the prognostic factors. The multivariate analysis revealed that metastatic pancreatic cancer (P = 0.046), no treatment (P < 0.001), worse ECOG-PS (P = 0.002), and high NLR (P < 0.001) were independently associated with OS. We revealed that the high NLR could be an independent indicator of poor prognosis in patients with unresectable pancreatic cancer.

Development of Hepatocellular Carcinoma in a Patient with Chronic Hepatitis C 21 Years after Achieving a Sustained Virological Response to Interferon Therapy.

A 77-year-old man with chronic hepatitis C (CH-C) infection, who achieved a sustained virological response (SVR) to interferon (IFN) therapy, was followed up regularly. Before IFN therapy, he did not have metabolic diseases, and the histological diagnosis of his chronic hepatitis was stage-3 fibrosis. After achieving SVR, the fibrosis-4 (FIB-4) index level dropped once but gradually increased. 21 years after SVR, hepatocellular carcinoma (HCC) was diagnosed by dynamic computed tomography. The HCC was 12 mm in diameter. The HCC was treated with radiofrequency ablation. CH-C patients with advanced fibrosis require long-term follow-up, even after achieving SVR.

Two Revision Surgeries on Cemented Custom-made Tumor Prostheses.

We performed revision surgery in 2 patients for stem fracture of a cemented tumor prosthesis that occurred more than 25 years after the initial surgery. For revision, the global modular replacement system (GMRS) was used. However, as bone cement in the bone could not be adequately removed, stems with respective diameters of 11 and 12.5 mm were used. In revision surgery for cemented tumor prostheses, adequate removal of residual bone cement is optimal. However, when there is a risk of fracture, it may be appropriate to insert a thicker stem after reaming the femoral canal as much as possible, and then fix the stem using the cement-in-cement method.

Comprehensive geriatric assessment of effects of hospitalization and long-term rehabilitation of patients following lower extremity arthroplasty.

[Purpose] This study was performed to examine the effects of subacute physical therapy (PT) on activities of daily living (ADL), quality of life, and geriatric aspects of patients who underwent total knee arthroplasty (TKA) or total hip arthroplasty (THA). [Subjects] The subjects were TKA (n=56) and THA (n=39) patients who received PT on the first day of independent ADL (up to 2 weeks) and just prior to discharge (4 weeks). [Methods] The functional independence measure (FIM), grip strength, knee extension strength (KES), timed up and go (TUG) test, mini-mental state examination (MMSE), geriatric depression scale short form (GDS-15), fall efficacy scale (FES), and medical outcome study 8-item short-form health survey (SF-8) were used as outcome measure, and comorbidity involvement was also investigated. [Results] Improvements in FIM, KES, TUG, GDS-15, FES, and SF-8 scores were seen in both groups (effect size, 0.31-0.87). Poor PT effects were found for THA patients aged ≥65 years, for TKA and THA patients with an MMSE score ≤28, and for THA patients with two or more comorbidities. [Conclusion] Positive effects were seen in patients who received PT at 2-4 weeks after surgery. Thus, additional PT for approximately 2 weeks after the beginning of independent ADL may be beneficial.

Successful Use of Plasma Exchange in the Treatment of Corticosteroid-Refractory Eosinophilic Granulomatosis with Polyangiitis Associated with Gastrointestinal Manifestations.

We describe the case of a 33-year-old woman having corticosteroid-refractory eosinophilic granulomatosis with polyangiitis (EGPA) who presented with abdominal pain and responded dramatically to plasma exchange. Eosinophilia, asthma history, neuropathy, pulmonary infiltrates, and paranasal sinus abnormalities confirmed the diagnosis of EGPA. Treatment was initiated with 1 g/day of methylprednisolone pulse therapy for 3 days followed by 60 mg/day of intravenous prednisolone without relieving abdominal pain. Then, plasma exchange was performed thrice. Abdominal pain disappeared after the first plasma exchange. Indication of plasma exchange for EGPA remains controversial; however, it may represent a valid option in cases with gastrointestinal involvement.

Association between increased blood interleukin-6 levels on emergency department arrival and prolonged length of intensive care unit stay for blunt trauma.

BACKGROUND: Systemic immune response to injury plays a key role in the pathophysiological mechanism of blunt trauma. We tested the hypothesis that increased blood interleukin-6 (IL-6) levels of blunt trauma patients on emergency department (ED) arrival are associated with poor clinical outcomes, and investigated the utility of rapid measurement of the blood IL-6 level. METHODS: We enrolled 208 consecutive trauma patients who were transferred from the scene of an accident to a level I trauma centre in Japan and admitted to the intensive care unit (ICU). Blood IL-6 levels on ED arrival were measured by using a rapid measurement assay. The primary outcome variable was prolonged ICU stay (length of ICU stay > 7 days). The secondary outcomes were 28-day mortality, probability of survival and Abbreviated Injury Scale (AIS) scores. RESULTS: Patients with prolonged ICU stay had significantly higher blood IL-6 levels on ED arrival than the patients without prolonged ICU stay (P < 0.0001). The receiver-operating characteristic curves produced an area under the curve of 0.75 (95 % confidence interval [CI], 0.66-0.84; P < 0.0001) for prolonged ICU stay. The patients who had increased blood IL-6 levels on ED arrival had increased 28-day mortality (P = 0.021) and decreased probability of survival (P < 0.0001). The AIS scores for the thorax, abdomen, extremity, and external body regions independently correlated with blood IL-6 levels (unstandardized coefficients [95 % CI] for the thorax: 23.8 [12.6-35.1]; P < 0.0001; abdomen: 42.7 [23.8-61.7]; P < 0.0001; extremity: 19.0 [5.5-32.4]; P = 0.0060; external body regions: 62.9 [13.2-112.7]; P = 0.030); the standardized coefficients for the thorax (0.27) and abdomen (0.28) were larger than those for the extremity (0.18) and external body regions (0.15). CONCLUSIONS: Increased blood IL-6 level on ED arrival was significantly associated with prolonged length of ICU stay. Blood IL-6 level on ED arrival independently correlated with the AIS scores for the abdomen and thorax, and, to a lesser extent, those for the extremity and external body regions. The rapid measurement of blood IL-6 level on ED arrival can be utilized as a fast screening tool to improve assessment of injury severity and prediction of clinical outcomes in the initial phase of trauma care.

Physical Activity Promotes Gait Improvement in Patients With Total Knee Arthroplasty.

BACKGROUND: The study aimed to examine whether the improvement in gait function after total knee arthroplasty (TKA) correlated with the amount of physical activity and whether both gait self-efficacy and gait function are predictors of the amount of physical activity up to 6 months after surgery. METHODS: Eighty-one patients were tested preoperatively and at the first and sixth postoperative months after TKA. Physical performance (timed up and go [TUG], sit to stand, muscle strength) and the modified gait efficacy scale scores were evaluated. The average amount of physical activity during the 6 postoperative months was measured with a pedometer with triaxial accelerometer. Stepwise multiple regression analyses were performed using TUG changes and postoperative physical activity. The discriminative properties of physical activity for improvement in gait function were subsequently investigated by applying a receiver operating characteristic curve analysis. RESULTS: The multiple regression analyses indicated that the amount of physical activity and the improvement in sit-to-stand time were important in predicting improvement in TUG scores after TKA, and postoperative physical activity up to 6 months was predicted by the modified gait efficacy scale and TUG scores at the first postoperative month. The receiver operating characteristic curve analysis suggests that with a cutoff point of 3053 steps/d, the amount of physical activity may be a good predictive factor for gait function after TKA. CONCLUSION: The clinical implications are that increases in physical activity can promote improvement in gait function after TKA and present with a solid numerical target for the recommended amount of physical activity.

Inhibition of human osteosarcoma cell migration and invasion by a gene silencer, pyrrole-imidazole polyamide, targeted at the human MMP9 NF-κB binding site.

Osteosarcoma is one of the most prevalent bone tumors, occurring mostly in adolescence. However, no noticeable progress has been achieved in developing new therapeutic agents for this disease. Matrix metalloproteinase 9 (MMP9), a type IV collagenase, is a known anticancer target and is overexpressed in osteosarcomas. MMPs can degrade components of the extracellular matrix and are known to be involved in tumor invasion and metastasis. In the present study, we designed and synthesized a pyrrole-imidazole polyamide (HN.49), a gene-silencing agent that specifically targets the nuclear factor-kappa B (NF-κB) binding site of the human MMP9 promoter. We then examined the effect of HN.49 on the enzyme activity of MMP9 and the migration activity of osteosarcoma cells in vitro. It was clearly shown that HN.49 polyamide reduced the expression level of MMP9 mRNA and the enzymatic activity of MMP-9 in SaOS-2 cells. Moreover, HN.49 polyamide inhibited migration and invasion by SaOS-2 cells in in vitro wound-closure and matrigel-invasion assays. These results indicate that HN.49 may be a potential therapeutic agent for inhibiting the invasion and metastasis of osteosarcoma.