Abnormalities of the pericruciate fat pad: Correlations with the location and severity of chondral lesions of the knee.

PURPOSE: The aim of this study was to evaluate the relationship between the grade of signal change of the pericruciate fat pad (PCFP) and the location and severity of cartilage alterations in the knee on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study included 234 patients (M:F = 96:138, mean: 51 years) who underwent knee MRI. Two experienced musculoskeletal radiologists assessed any PCFP alterations (as grades 0-3) and chondral lesions using the modified Outerbridge grade (as grades 0-4). Bone marrow lesions (BMLs), meniscal status, anterior cruciate ligament alterations, and effusion-synovitis were also evaluated on the MRI. The relationships between PCFP alteration and MR findings (including the grade of chondral lesion) were evaluated. RESULTS: Signal changes in the PCFP were detected in 150 cases by Reader 1 (grade 0, 67 cases; grade 1, 53 cases; grade 2, 21 cases; grade 3, 9 cases) and in 154 cases by Reader 2 (grade 0, 59 cases; grade 1, 61 cases; grade 2, 24 cases; grade 3, 10 cases). The grade of PCFP signal change was statistically significantly correlated with the grade of the chondral lesion of the medial femoral condyle (MFC) (p = 0.029 and p = 0.003, respectively) and the medial tibial plateau (MTP) (p = 0.045, p = 0.002, Readers 1 and 2, respectively). The grade of PCFP signal change was significantly correlated with the grade of the BMLs of the MFC, MTP, and lateral femoral condyle (p < 0.05) for both readers. PCFP alteration was related to effusion-synovitis and tears of the medial meniscus. CONCLUSIONS: The grade of PCFP signal change was correlated with the severity of the cartilage alteration in the medial compartment of the knee joint and was also correlated with BMLs in the medial compartment, medial meniscal tears, and synovitis. Therefore, signal change in the PFCP seen on MRI can be an additional clue of the presence of osteoarthritis in the knee, particularly in the medial compartment.

The Association of Carbohydrate Antigen (CA) 19-9 Levels and Low Skeletal Muscle Mass in Healthy Adults.

Carbohydrate antigen 19-9 (CA 19-9) is a commonly used tumor marker for pancreatic cancer. However, CA 19-9 can be overexpressed in several benign inflammatory diseases. We investigated the relationship between high CA 19-9 level and low muscle mass (LMM) in healthy adults without cancer. Participants who underwent evaluation of muscle mass and CA 19-9 were included. Exclusion criteria were any malignancy, cardiovascular disease, tuberculosis, and chronic lung/liver disease. Participants were classified into "normal", "mild LMM", and "severe LMM" groups based on the skeletal muscle mass index. Multivariable logistic regression analyses were conducted to assess the association of high CA 19-9 with muscle mass status. A total of 263,061 adults were included. The mean age and SMI were 41.03 years and 7.13 kg/m2. After adjustments for various confounders, high CA 19-9 was independently associated with mild LMM (adjusted odds ratio, 1.677 [95% confidence interval, 1.533-1.834]) and severe LMM (2.651 [2.126-3.306]) compared to the normal group. Furthermore, the association between high CA 19-9 and severe LMM was stronger in men than in women. Elevated CA 19-9 levels were independently associated with a higher prevalence of LMM in healthy adults without cancer. Therefore, increased CA 19-9 could be utilized as a novel biomarker for sarcopenia.

Sex-specific associations between gut microbiota and skeletal muscle mass in a population-based study.

BACKGROUND: A gut-muscle axis through which the microbiome influences skeletal muscle has been hypothesized. However, sex-specific association between the characteristics of gut microbiota and skeletal muscle mass has not yet been reported. Herein, we performed sex-specific analyses of faecal microbiota composition for the skeletal muscle mass in a population-based cohort. METHODS: We collected faecal samples of 1052 middle-aged participants (621 men and 431 women) who attended health screenings, and we analysed the intestinal microbiota using 16S rRNA gene sequencing. Relative muscle mass was calculated using a bioelectrical impedance analysis and presented as the skeletal muscle mass index [SMI (%) = total appendicular muscle mass (kg)/weight (kg) × 100]. We categorized the subjects into four groups by the quartile of the SMI. Association tests between gut microbiota and SMI were conducted according to the microbial diversity, taxonomic profiling and functional inference in a sex-stratified manner. RESULTS: The mean age and SMI of the total participants were 44.8 years (standard deviation [SD], 8.2) and 41.4% (SD, 3.9), respectively. After adjustments for possible covariates such as age, body mass index and regular physical activity, the highest quartile (Q4) group of SMI had higher alpha diversity than the lowest quartile (Q1) group in male participants (coefficient = 10.79, P < 0.05, linear regression model), whereas there was no difference in diversity among SMI groups in females. At the species level, Haemophilus parainfluenzae (coefficient = 1.910) and Roseburia faecis (coefficient = 1.536) were more abundant in the highest SMI (Q4) group than in the lowest SMI (Q1) group in males. However, no significant taxon was observed along the SMI groups in females. The gut microbiota of the lowest SMI group (Q1) was enriched with genes involved in biosynthesis of amino acids and energy generation compared with that of the highest SMI group (Q4) in both sexes, although the significance of the inferred pathways was weak (P < 0.05 but the false discovery rate q > 0.05). CONCLUSIONS: In this large sample of middle-aged individuals, this study highlights fundamental sex-specific differences in the microbial diversity, composition and metabolic pathways inferred from gut microbiota according to SMI. The gut microbiota may provide novel insights into the potential mechanisms underlying the sex dependence of skeletal muscle mass.

Increased Carcinoembryonic Antigen (CEA) Level Is Highly Associated with Low Skeletal Muscle Mass in Asymptomatic Adults: A Population-Based Study.

We investigated the relationship between high carcinoembryonic antigen (CEA) levels and low skeletal muscle mass (LMM) in asymptomatic adults in a population-based study. A total of 202,602 adults (mean age 41.7 years) without malignancy, stroke, cardiovascular disease, or chronic lung/liver disease were included. A high CEA level was defined as ≥5 ng/mL. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: "normal", "mild LMM", and "severe LMM." The prevalence of elevated CEA levels was the highest in subjects with severe LMM (4.2%), followed by those with mild LMM (1.6%) and normal muscle mass (1.1%) (p for trend < 0.001). In multivariate logistic regression analysis, high CEA was independently associated with having mild LMM (adjusted odds ratio, 1.139 [95% confidence interval, 1.092−1.188]) and severe LMM (2.611 [2.055−3.319]) compared to normal muscle mass. Furthermore, the association between high CEA and severe LMM was stronger in women than that in men (women, 5.373 [2.705−10.669]; men, 2.273 [1.762−2.933]). Elevated CEA levels were significantly associated with a higher prevalence of LMM. Therefore, increased CEA could be used as a biomarker for detecting LMM in adults without cancer.

Association between Elevated Plasma Homocysteine and Low Skeletal Muscle Mass in Asymptomatic Adults.

BACKGROUND: Homocysteine has been drawing attention with a closed linkage with skeletal muscle. However, the association of hyperhomocysteinemia with decreased skeletal muscle mass remains unclear. We aimed to investigate the association of hyperhomocysteinemia with low skeletal muscle mass (LMM) in asymptomatic adults. METHODS: This was a cross-sectional study of 114,583 community-dwelling adults without cancer, stroke, or cardiovascular diseases who underwent measurements of plasma homocysteine and body composition analysis from 2012 to 2018. Hyperhomocysteinemia was defined as >15 µmol/L. Skeletal muscle mass index (SMI) was calculated based on appendicular muscle mass (kg)/height (m)2. Participants were classified into three groups based on SMI: "normal," "mildly low," and "severely low." RESULTS: The prevalence of hyperhomocysteinemia was the highest in subjects with severely LMM (12.9%), followed by those with mildly LMM (9.8%), and those with normal muscle mass (8.5%) (P for trend <0.001). In a multivariable logistic regression model, hyperhomocysteinemia was significantly associated with having a mildly LMM (odds ratio [OR], 1.305; 95% confidence interval [CI], 1.224 to 1.392) and severely LMM (OR, 1.958; 95% CI, 1.667 to 2.286), respectively. One unit increment of log-transformed homocysteine was associated with 1.360 and 2.169 times higher risk of having mildly LMM and severely LMM, respectively. CONCLUSION: We demonstrated that elevated homocysteine has an independent association with LMM in asymptomatic adults, supporting that hyperhomocysteinemia itself can be a risk for decline in skeletal musculature.

Postsurgical status of articular cartilage after arthroscopic posterior cruciate ligament reconstruction in patients with or without concomitant meniscal pathology.

PURPOSE: Several factors present at the time of posterior cruciate ligament reconstruction (PCLR) may cause the subsequent progression of articular cartilage lesions. This study aimed to evaluate postsurgical articular cartilage lesions which can be seen on MRI in patients who underwent arthroscopic PCLR with or without concomitant meniscal pathology. MATERIAL AND METHODS: A total of sixty-five patients (mean age 35.8 ± 12.3 years) who underwent arthroscopic PCLR were included in this retrospective study. Patients were divided into two groups: ten patients with concomitant meniscal injuries at the time of PCLR who underwent meniscal surgery and fifty-five patients with intact menisci. The cartilage status of all knees was evaluated by MRI and modified Noyes classification. RESULTS: Cartilage lesions were observed in 18 patients (27.7%) on the last follow-up MRI. The cartilage lesions were more common in the medial (15.4%) and patellofemoral (12.3%) compartments than in the lateral compartment (7.7%). Progression of cartilage lesions was present in 11 patients (16.9%) during follow-up MRI. The majority of cartilage lesions with progression were located in the medial compartment. The meniscal pathology group showed a higher prevalence of articular cartilage lesions on the last follow-up MRI (21.8% versus 60%, p = 0.022). In multivariate Cox regression, concomitant meniscal pathology was significantly associated with progression of articular cartilage lesions (p = 0.044). CONCLUSION: PCLR patients with associated meniscal pathology showed worse cartilage condition and more progression of cartilage lesions than isolated PCLR patients. Attention to this risk factor might provide more applicable treatment options for potential osteoarthritis prevention strategies.

Can ultrasound distinguish between dermatofibroma and subcutaneous epidermal tumors? - Imaging features and reproducibility.

BACKGROUND: We evaluated ultrasound (US) features of dermatofibroma and epidermal tumor (ET). We also evaluated the reproducibility of each US findings. MATERIALS AND METHODS: We retrospectively assessed US findings of 30 surgically confirmed dermatofibromas and 44 ETs, measuring the lesion (i.e., the depth and the length of the lesion) and calculating the depth to length ratio (DLR). We then determined the sharpness and the shape of the lesion. Finally, we assessed whether the lesion appeared with a "more-than-half sign" (involving more than 50% of the dermal layer) or a "submarine sign" (focal projection to skin). We used Pearson's chi-squared test to analyze the US findings (i.e., presence of more-than-half sign or submarine sign and margin sharpness) between dermatofibroma and ET. Inter-observer agreement of the image findings was assessed using kappa statistics. RESULTS: The submarine sign and margin sharpness of ET lesions and the more-than-half sign and submarine sign in dermatofibroma, respectively, showed almost perfect agreement. Also, the more-than-half sign and shape of the lesion in ET and the margin sharpness and shape of the lesion in dermatofibroma showed substantial agreement. The measurements of DLRs showed excellent reproducibility. There were no significant differences of DLRs between two groups (p values = 0.512, 0.671, respectively). The more-than-half sign was observed more frequently in the context of dermatofibroma to a statistically significant degree (p < 0.001), while the submarine sign was statistically more common in relation to ET together with greater margin sharpness (p = 0.021 and <0.001, respectively). CONCLUSIONS: More-than-half signs are common in dermatofibroma while submarine sign and sharp margin are common in ET. Each finding showed high reproducibility and can be useful as a sonographic marker for differentiation between ET and dermatofibroma.

Follow-up of clinical and sonographic features after extracorporeal shock wave therapy in painful plantar fibromatosis.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been used as a safe alternative treatment for refractory musculoskeletal diseases, such as plantar fasciitis, Achilles tendinopathy and gluteal tendinopathy, and various forms of fibromatosis including palmar or penile fibromatosis. However, there is limited published data for clinical and sonographic features of plantar fibromatosis after ESWT. The purpose of this study was to evaluate the long-term clinical outcome of ESWT in ultrasonography-confirmed plantar fibromatosis and ultrasonographic changes of plantar fibroma after ESWT. METHODS: Medical charts of 26 patients (30 feet) with plantar fibromatosis confirmed by ultrasonography were reviewed. Finally, a total of 10 feet who underwent ESWT for "Poor" or "Fair" grade of Roles-Maudsley Score (RMS) and symptoms persisted for >6 months were included in this study. Short-term follow-up was conducted one week after ESWT and long-term follow-up time averaged 34.0 months. The Numerical Rating Scale (NRS) and RMS were collected for the evaluation of clinical features. Follow-up ultrasonography was conducted at long-term follow-up and changes of plantar fibroma was assessed. A greater than 50% reduction in the NRS and achievement of a "good" or "excellent" grade in the RMS were regarded as treatment success. Additionally, medical charts of 144 patients (168 feet) with plantar fasciitis confirmed by ultrasonography were reviewed and subsequently, 42 feet who underwent ESWT with the same protocol were included for the comparison of clinical features. RESULTS: In plantar fibromatosis, baseline NRS (6.2 ± 1.3) and RMS (3.5 ± 0.5) were significantly improved at short-term follow-up (NRS, 1.8 ± 1.0; RMS, 2.0 ± 0.8, P < .001, respectively) and long-term follow-up (NRS, 0.6 ± 1.1; RMS, 1.4 ± 0.8, P < .001, respectively). Treatment success was recorded in seven feet (70.0%) at short-term follow-up and 8 feet (80%) at long-term follow-up, which is comparable to that of the plantar fasciitis group (28 feet, 66.7%; 35 feet, 83.3%, respectively). In long-term follow-up ultrasonography, mean fibroma thickness was reduced from 4.4±1.0 to 2.6±0.8 mm (P = .003); however, length and width were not significantly changed. There were no serious adverse effects. CONCLUSION: While these are preliminary findings, and must be confirmed in a randomized placebo control study, ESWT can have a beneficial long-term effect on pain relief and functional outcomes in painful plantar fibromatosis. However, ESWT is unlikely to affect the ultrasonographic morphology of plantar fibroma, with the exception of reducing the thickness. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Association between underweight and pulmonary function in 282,135 healthy adults: A cross-sectional study in Korean population.

In contrast to obesity, studies on the relationship between underweight and pulmonary function are still sparse. Thus, the objective of this study was to investigate the effect of being underweight on pulmonary function in a general population without apparent lung disease. A total of 282,135 retrospective cohort subjects between January 2012 and December 2014 in Korea were included. Using multivariate-adjusted analysis, the relationship between body mass index (BMI) and pulmonary function were assessed. Underweight individuals represented 5.5% of the total study population (n = 282,135), with most (87.9%) of them being females. Compare to normal weight and obese, underweight was associated with decreased pulmonary function. Forced expiratory volume in first second (FEV1), predicted FEV1 (%), forced vital capacity (FVC), predicted FVC (%), and peak expiratory flow (PEF) were lower in the underweight group than those in other groups after adjusting for age, sex, height, status of smoking, frequency of vigorous exercise, diabetes, and high-sensitivity C-reactive protein (hsCRP) (P < 0.001). Lower BMI tended to decrease pulmonary function parameters such as FEV1 (L), predicted FEV1 (%), FVC (L), predicted FVC (%), and PEF (L/sec) (P for trend <0.001). After adjusting for possible confounders, odds ratios (ORs; 95% confidence interval) for subjects with predicted FEV1% < 80% in underweight and normal weight groups compared to obese group (reference) were 2.10 (1.98-2.21), and 0.93 (0.90-0.97), respectively. ORs for subjects with predicted FVC% < 80% in underweight and normal weight groups compared to obese group (reference) were 4.90 (4.62-5.18) and 1.32 (1.27-1.38), respectively. This study demonstrated a proportional relationship between pulmonary function and the degree of BMI. We found that underweight status was independently associated with decreased pulmonary function in Korean population.

Long-term outcome of low-energy extracorporeal shockwave therapy on gluteal tendinopathy documented by magnetic resonance imaging.

BACKGROUND: Previous outcome studies for extracorporeal shock wave therapy (ESWT) have included clinically diagnosed greater trochanteric pain syndrome (GTPS). The purpose of this study is to investigate outcome of ESWT on GTPS with gluteal tendinopathy documented by magnetic resonance imaging (MRI). METHODS: Medical records of 38 consecutive patients were retrospectively reviewed, who underwent ESWT for GTPS with MRI-documented gluteal tendinopathy (> 6 months). ESWT was conducted (1/week) when the Roles-Maudsley score (RMS) showed "Poor" or "Fair" grade after conservative treatment until RMS had reached "Good" or "Excellent" grade (treatment success) or until 12 treatments had been applied. Numeric rating scale (NRS) and RMS were evaluated before, 1 week after (immediate follow-up) and mean 27 months after ESWT program (long-term follow-up). Success rate was calculated at each follow-up point. RESULTS: Initial NRS (5.9 ± 1.6) significantly decreased at immediate (2.5 ± 1.5, p< 0.01) and long-term follow-up (3.3 ± 3.0, p< 0.01), respectively. Success rates were 83.3% (immediate) and 55.6% (long-term), respectively. There was no correlation among age, symptom duration and NRS. CONCLUSION: Low-energy ESWT can be an effective treatment for pain relief in chronic GTPS with MRI-documented gluteal tendinopathy. However, its long-term effect appears to decrease with time.

Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly, small interfering RNA-transfected knockdown of the migration inhibitory factor gene in methylglyoxal-treated skin keratinocytes increased expression of glyoxalase-I and intraepidermal nerve fibers in comparison with control small interfering RNA-transfected cells, which was decreased by induction of methylglyoxal. Conclusions Our findings suggest that migration inhibitory factor can aggravate diabetic neuropathy by suppressing glyoxalase-I and intraepidermal nerve fibers on the footpad skin lesions and provoke pain. Taken together, migration inhibitory factor might offer a pharmacological approach to alleviate pain syndromes in diabetic neuropathy.

Effect of high frequency electromagnetic wave stimulation on muscle injury in a rat model.

INTRODUCTION: The aim of this study was to investigate biological changes in tissues with muscle contusion after the application of high frequency (HF) electromagnetic wave. METHODS: An acrylic pipe was placed on the right hind limb and a metallic ball was dropped inside the pipe, which resulted in a muscle contusion. After acquiring the optimal condition for muscle contusion, 20 Sprague-Dawley rats were allocated to the HF treatment (N = 10) and sham groups (N = 10), which then underwent muscle contusion injury at their right thigh. The thickness and circumference of the right thigh and the left thigh (negative control groups) were measured (day 0). HF electromagnetic wave stimulation for three days was performed on the contusion area in the HF group after one day. Thickness was measured at the thickest area of both hind limbs and the circumference was measured every day for three days. The sham group received no treatment, and the circumference and thickness were measured using the same method. After three days, Hematoxylin and eosin and immunohistochemical (IHC) staining for IL-1ß were performed and TUNEL assay was conducted for apoptosis in the skin and muscle layers. RESULTS: The thigh muscle thickness at day 1 was significantly different between groups (P = 0.018) and this difference was observed between both sham and control groups (corrected P = 0.007), and between sham and HF groups (corrected P = 0.043). Thigh circumference was significantly different at day 3 (P = 0.047) and this difference was found between sham and control groups (corrected P = 0.018), and between sham and HF groups (corrected P = 0.032). In the HF group, the inflammatory response was reduced to almost the same level as the control group. Evaluation of IL-1ß level, the inflammatory cytokine, through IHC showed marked localization of IL-1ß in muscle fibers of the sham group. However, significantly less IL-1ß was observed in the muscle of the HF treatment group. There was neither injury nor apoptosis after HF stimulation. CONCLUSIONS: Application of the HF showed therapeutic effect on muscle contusion by reducing muscle swelling. This effect might be caused by the anti-inflammatory action of the HF, which evoked energy into the injured muscle.

A Clinical Comparative Study of Ultrasound-Normal Versus Ultrasound-Abnormal Congenital Muscular Torticollis.

OBJECTIVE: To investigate the clinical features and outcome of outpatient-based physiotherapy (manual stretch) of congenital muscular torticollis (CMT) with passive neck motion limitation (≥ 10°) according to whether the finding on ultrasonography (US) is normal or abnormal. DESIGN: Case-control study. SETTING: Institutional practice. PARTICIPANTS: A total of 149 patients with CMT who met eligibility criteria were included: age at presentation ≤ 6 months, limitation of passive neck rotation (ΔROT) or lateral flexion (ΔLAT) ≥ 10°, and completion of our outpatient-based physiotherapy program. INTERVENTIONS: Patients were allocated to the US-normal or US-abnormal group. Patients underwent physiotherapy and were followed-up monthly until ΔROT and ΔLAT were ≤ 5° or did not respond to treatment. MAIN OUTCOME MEASUREMENTS: Baseline characteristics, initial ΔROT and ΔLAT, age at presentation, treatment durations, and success rates of physiotherapy were compared between 2 groups. Treatment duration was adjusted for initial ΔROT, ΔLAT, and age at presentation using analysis of covariance. RESULTS: Mean initial ΔROT and ΔLAT in US-abnormal (28.5°; 17.0°) were greater than in US-normal (7.9°, P < .001; 12.3°, P = .001, respectively). Mean age at presentation was older in US-normal (3.8 months) than in US-abnormal (1.8 months, P < .001). Treatment duration was shorter in the US-normal (5.1 weeks) than US-abnormal (14.9 weeks, P < .001). Adjusted treatment duration was also shorter in US-normal (9.7 weeks) than US-abnormal (13.8 weeks, P < .05). The success rates of physiotherapy were 95% in US-abnormal and 100% in US-normal. Two of 6 treatment failures in the US-abnormal group underwent surgery. CONCLUSIONS: In CMT with passive neck motion limitation (≥ 10°), patients in the US-normal group demonstrated lesser passive neck motion limitation and older age at presentation than US-abnormal. It seems that US-normal showed shorter treatment duration irrespective of severity of neck motion limitation and age at presentation. Additionally, manual stretching applied before 6 months of age appears to show generally good outcome regardless of US findings.

Paradoxical effects of human adipose tissue-derived mesenchymal stem cells on progression of experimental arthritis in SKG mice.

We evaluated the therapeutic effect of human adipose tissue-derived mesenchymal stem cells (hAd-MSCs) in a SKG arthritis model, a relevant animal model for human rheumatoid arthritis. hAd-MSCs were administered intraperitoneally into the mice for five consecutive days from on day 12 or 34 after arthritis induction, when the average clinical score was 0.5 or 5, respectively. They remarkably suppressed arthritis when administered on day 12. Disease suppression was correlated with reduction of pro-inflammatory cytokines and with increased levels of TGF-ß and IL-10 from splenocytes. However, when hAd-MSCs were administered on day 34, the clinical scores were not improved, the histopathological scores were aggravated, and cytokine profiles were differed. Thus, hAd-MSCs showed paradoxical effects, according to the disease phase when they were administered. These suggest that the same cells acted differently depending on the disease progress, and cautions should be paid for safe and effective use of MSCs.

Suppression of in vitro murine T cell proliferation by human adipose tissue-derived mesenchymal stem cells is dependent mainly on cyclooxygenase-2 expression.

Mesenchymal stem cells (MSCs) of human origin have been frequently applied to experimental animal models to evaluate their immunomodulatory functions. MSCs are known to be activated by cytokines from T cells, predominantly by interferon-γ (IFN-γ), in conjunction with other cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-1ß. Because IFN-γ is not cross-reactive between human and mouse species, the manner in which human MSCs administered in experimental animals are activated and stimulated to function has been questioned. In the present study, we established MSCs from human adipose tissue. They successfully suppressed the proliferation of not only human peripheral blood mononuclear cells but also mouse splenic T cells. When these human MSCs were stimulated with a culture supernatant of mouse T cells or recombinant murine TNF-α, they expressed cyclooxygenase-2 (COX-2), but not indoleamine 2,3-dioxygenase. The dominant role of COX-2 in suppressing mouse T cell proliferation was validated by the addition of COX-2 inhibitor in the co-culture, wherein the suppressed proliferation was almost completely recovered. In conclusion, human MSCs in a murine environment were activated, at least in part, by TNF-α and mainly used COX-2 as a tool for the suppression of in vitro T cell proliferation. These results should be considered when interpreting results for human MSCs in experimental animals.

IL-1ß induction and IL-6 suppression are associated with aggravated neuronal damage in a lipopolysaccharide-pretreated kainic acid-induced rat pup seizure model.

OBJECTIVES: Reportedly, hippocampal neuronal degeneration by kainic acid (KA)-induced seizures in rats <14 days old was enhanced by lipopolysaccharide (LPS). This study was to test the hypothesis that cytokines such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α are associated with aggravated neuronal damage. MATERIALS AND METHODS: Sixty male Sprague-Dawley, 14-day-old rats were used. Experiments were conducted in saline, LPS + saline, saline + KA and LPS + KA groups. Intraperitoneal LPS injections (0.04 mg/kg) were administered 3 h prior to KA injection (3 mg/kg). RESULTS: The LPS + KA group showed a tendency toward shorter latency to seizure onset (p = 0.086) and significantly longer seizure duration (p < 0.05) compared with the KA group. Induction of the proconvulsant cytokine IL-1ß in rat pup brains was significantly greater in the LPS + KA group compared to the KA group (38.8 ± 5.5 vs. 9.2 ± 1.0 pg/µg; p < 0.05); however, IL-6 levels were higher in the KA group than in the LPS + KA group (108.7 ± 6.8 vs. 60.9 ± 4.7 pg/µg; p < 0.05). The difference in tumor necrosis factor-α between the LPS + KA group and the KA group was insignificant (12.1 ± 0.6 vs. 10.9 ± 2.3 pg/µg; p = 0.64). CONCLUSIONS: Our results showed an increase in the proconvulsant cytokine IL-1ß and a decrease in a potentially neuroprotective cytokine, IL-6, in rat pups treated with LPS + KA. These results warrant further investigation into the possible role of IL-1ß induction and IL-6 suppression in LPS-promoted neuronal damage.

Clinical features and outcome of physiotherapy in early presenting congenital muscular torticollis with severe fibrosis on ultrasonography: a prospective study.

BACKGROUND: It has been reported that ultrasonography (US) can detect the severity of congenital muscular torticollis (CMT), and severe fibrosis of the sternocleidomastoid (SCM) muscle noted on US is irreversible and likely to require surgery. Clinical outcome of CMT depends mainly on the patient's age, which is also associated with the severity of fibrosis as determined by US. However, there has been no well-designed study to elucidate the true relationship among these factors nor a definite consensus on treatment of young infants with severe fibrosis in the SCM compared with well-documented reports that late cases require surgery. PURPOSE: The purpose of the current study was to investigate whether severity of SCM fibrosis on US is correlated with clinical severity and outcome of standardized physiotherapy in early presenting CMT. METHODS: Fifty patients with a palpable neck mass, initial deficit of passive neck rotation (ΔROT) more than 10°, and age less than 3 months were classified into 4 US types according to the severity of fibrosis in the SCM and underwent standardized physiotherapy and regular assessment. Relationship between US types and 2 variables (ΔROT and treatment duration) and success rate of physiotherapy was assessed. RESULTS: None of the cases was classified as type 4. Type 3 showed greatest ΔROT and longest mean treatment duration. Both variables showed a significant linear trend of association with US types by P for trend (P = .003, P < .001, respectively). Treatment was "successful" in 49 patients (98%). CONCLUSION: In young infants with CMT, US can document severity; and an early and adequate physiotherapy is a good treatment option, particularly even in those with severe fibrosis.

Risk factors for intrauterine constraint are associated with ultrasonographically detected severe fibrosis in early congenital muscular torticollis.

BACKGROUND/PURPOSE: The etiology of congenital muscular torticollis (CMT) remains controversial. Ultrasonographically, severe fibrosis involving the entire sternocleidomastoid muscle (SCM; type 3 or 4) fibrosis has been associated with poor clinical outcomes and indicates a chronic state of the condition. The purpose of this study was to test whether or not type 3 or 4 fibrosis detected early after birth is associated with factors related to prolonged intrauterine constraint. METHODS: Sixty-seven patients (age, <3 months) with CMT were classified into 4 different ultrasonographic types according to the severity of SCM fibrosis. The odds ratio for the relationship between probability of type 3 or 4 and factors related to intrauterine constraint were calculated by a multivariate logistic regression model. RESULTS: None were classified as type 4. Twenty-three patients (34%) had a history of breech presentation, and 21 (91.3%) of them were delivered by elective cesarean section without likelihood of birth trauma. Compared with normal pregnancy, breech presentation and oligohydramnios showed a 6.7 or 7.5 times higher probability for type 3 fibrosis, respectively. CONCLUSION: Risk factors for intrauterine constraint appear to be associated with ultrasonographically detected severe fibrosis involving the entire SCM muscle in early presenting CMT.

Effect of quilting sutures on hematoma formation after liposuction with dermal curettage for treatment of axillary hyperhidrosis: a randomized clinical trial.

BACKGROUND: Liposuction provides further reduction of axillary sweating and malodor when combined with dermal curettage with sharp rasping cannulas. This aggressive approach is associated with relatively higher rate of hematoma formation when compared to the conventional simple liposuction. OBJECTIVE: The aim of this prospective, randomized, controlled trial was to evaluate the effect of quilting sutures on the incidence of hematoma formation after liposuction-curettage for treatment of axillary hyperhidrosis (AH). MATERIALS AND METHODS: The trial randomized 59 male patients (118 axillae) undergoing liposuction-curettage for AH to quilting procedures (61 axillae) or control group (57 axillae) for intention-to-treat analysis. Outcome measures included the incidence of hematoma formation, operative time, degree of postoperative pain, and amount of analgesics consumption. RESULTS: Quilting sutures significantly reduced the incidence of axillary hematoma from 28.1% to 4.9%. Quilting was associated with the lengthening of operative time but did not affect the postoperative pain. CONCLUSION: Considering its efficacy in reducing postoperative hematoma, quilting is recommended in combination with aggressive liposuction-curettage procedure for treating AH and osmidrosis.