Vitamin D Inadequacy Affects Skeletal Muscle Index and Physical Performance in Lumbar Disc Degeneration.

Lumbar disc degeneration (LDD) is one of the fundamental causes of low back pain. The aims of this study were to determine serum 25-hydroxyvitamin D (25(OH)D) levels and physical performance and to investigate the relationship between serum vitamin D levels, muscle strength and physical activity in elderly patients with LDD. The participants were 200 LDD patients, including 155 females and 45 males aged 60 years and over. Data on body mass index and body composition were collected. Serum 25(OH)D and parathyroid hormone levels were measured. Serum 25(OH)D was classified into the insufficiency group: <30 ng/mL and the sufficiency group: ≥30 ng/mL. Muscle strength was assessed by grip strength, and physical performance (short physical performance battery) was evaluated by the balance test, chair stand test, gait speed, and Timed Up and Go (TUG) test. Serum 25(OH)D levels in LDD patients with vitamin D insufficiency were significantly lower than in those with vitamin D sufficiency (p < 0.0001). LDD patients with vitamin D insufficiency had a prolonged time in physical performance on gait speed (p = 0.008), chair stand test (p = 0.013), and TUG test (p = 0.014) compared to those with vitamin D sufficiency. Additionally, we found that serum 25(OH)D levels were significantly correlated with gait speed (r = -0.153, p = 0.03) and TUG test (r = -0.168, p = 0.017) in LDD patients. No significant associations with serum 25(OH)D status were observed for grip strength and balance tests among patients. These findings demonstrate that higher serum 25(OH)D levels are associated with better physical performance in LDD patients.

Neutralizing Activities Against the Omicron Variant After a Heterologous Booster in Healthy Adults Receiving Two Doses of CoronaVac Vaccination.

BACKGROUND: The use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) against SARS-CoV-2 is implemented worldwide. However, waning immunity and breakthrough infections have been observed. Therefore, we hypothesized that the heterologous booster might improve the protection against the delta and omicron variants. METHODS: A total of 224 individuals who completed the 2-dose CoronaVac for 6 months were included. We studied reactogenicity and immunogenicity after a heterologous booster with the inactivated vaccine (BBIBP), the viral vector vaccine (AZD1222), and the messenger ribonucleic acid (mRNA) vaccine (both BNT162B2 and mRNA-1273). We also determined immunogenicity at 3- and 6-month boosting intervals. RESULTS: The solicited adverse events were mild to moderate and well tolerated. Total receptor binding domain (RBD) immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T-cell response were highest in the mRNA-1273 group followed by the BNT162b2, AZD1222, and BBIBP groups, respectively. We also witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval group. CONCLUSIONS: All 4 booster vaccines significantly increased binding and neutralizing antibodies in individuals immunized with 2 doses of CoronaVac. The present evidence may benefit vaccine strategies to thwart variants of concern, including the omicron variant.

Telomere Shortening and Increased Oxidative Stress in Lumbar Disc Degeneration.

Lumbar disc degeneration (LDD) contributes to low back pain. This study aimed to determine relative telomere length (RTL), oxidative stress status, and antioxidant levels and examine the relationships between RTL, oxidative stress, and the severity in LDD patients. A total of 100 subjects, 50 LDD patients and 50 healthy controls, were enrolled in the case−control study. Blood leukocyte RTL was analyzed using quantitative real-time polymerase chain reaction. Lipid peroxidation was determined by malondialdehyde (MDA) assay. Plasma 8-hydroxy 2'-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay. Total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP) in plasma were also measured. The LDD patients had significantly shorter telomeres than the healthy controls (p = 0.04). Blood leukocyte RTL was inversely correlated with the LDD severity (r = −0.41, p = 0.005). Additionally, plasma MDA and 8-OHdG levels were markedly greater in LDD patients than in the controls (p = 0.01 and p = 0.002, respectively). Furthermore, the plasma MDA level showed a positive correlation with the radiographic severity (r = 0.49, p = 0.001). There was a positive correlation between plasma 8-OHdG and the severity (r = 0.60, p < 0.001). Moreover, plasma TAC and FRAP levels were significantly lower in LDD patients than in the controls (p = 0.04). No significant differences in plasma TAC and FRAP were observed among the three groups of LDD severity. We found that RTL was negatively correlated with the severity while plasma MDA and 8-OHdG levels were positively correlated with the severity. These findings suggest that blood leukocyte RTL, plasma MDA, and 8-OHdG may have potential as noninvasive biomarkers for the assessment of severity in LDD.

Telomere Length Is Correlated with Resting Metabolic Rate and Aerobic Capacity in Women: A Cross-Sectional Study.

This study investigated the associations between relative telomere length (RTL) and resting metabolic rate (RMR), resting fat oxidation (RFO), and aerobic capacity and whether oxidative stress and inflammation are the underlying mechanisms in sedentary women. We also aimed to determine whether the correlations depend on age and obesity. Sixty-eight normal weight and 66 obese women participated in this study. After adjustment for age, energy expenditure, energy intake, and education level, the RTL of all participants was negatively correlated with absolute RMR (RMRAB) and serum high-sensitivity C-reactive protein (hsCRP) concentration, and positively correlated with maximum oxygen consumption (V˙O2max) (all p < 0.05). After additional adjustment for adiposity indices and fat-free mass (FFM), RTL was positively correlated with plasma vitamin C concentration (p < 0.05). Furthermore, after adjustment for fasting blood glucose concentration, RTL was negatively correlated with age and positively correlated with V˙O2max (mL/kg FFM/min). We found that normal weight women had longer RTL than obese women (p < 0.001). We suggest that RTL is negatively correlated with RMRAB and positively correlated with aerobic capacity, possibly via antioxidant and anti-inflammatory mechanisms. Furthermore, age and obesity influenced the associations. We provide useful information for the management of promotion strategies for health-related physical fitness in women.

Cytokine Profiling and Intra-Articular Injection of Autologous Platelet-Rich Plasma in Knee Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease leading to joint pain and stiffness. Due to lack of effective treatments, physical and psychological disabilities caused by OA have a detrimental impact on the patient's quality of life. Emerging evidence suggests that intra-articular injection of platelet-rich plasma (PRP) may provide favorable results since PRP comprises not only a high level of platelets but also a huge amount of cytokines, chemokines, and growth factors. However, the precise mechanism and standardization method remain uncertain. This study aimed to examine cytokine profiling in both PRP and platelet-poor plasma (PPP) of knee OA patients and to determine the effects of PRP on OA chondrocytes and knee OA patients. PRP contained a wide variety of cytokines, chemokines, growth factors, and autologous intra-articular PRP injection resulted in favorable outcomes in knee OA patients. Significant increases in levels of IL-1, IL-2, IL-7, IL-8, IL-9, IL-12, TNF-α, IL-17, PDGF-BB, bFGF, and MIP-1ß were detected in PRP compared to PPP (p < 0.001). An in vitro study showed a marked increase in proliferation in OA chondrocytes cultured with PRP, compared to PPP and fetal bovine serum (p < 0.001). In a clinical study, knee OA patients treated with PRP showed improvement of physical function and pain, assessed by physical performance, Western Ontario and McMaster Universities Arthritis Index and visual analog scale. Our findings from both in vitro and clinical studies suggest that intra-articular PRP injection in knee OA patients may be a potential therapeutic strategy for alleviating knee pain and delaying the need for surgery.

Internalization of Neutrophil-Derived Microvesicles Modulates TNFα-Stimulated Proinflammatory Cytokine Production in Human Fibroblast-Like Synoviocytes.

Neutrophil-derived microvesicles (NDMVs) have the potential to exert anti-inflammatory effects. Our study aimed to explore the effects of NDMVs on proinflammatory cytokines expressed by tumor necrosis factor α (TNFα)-stimulated fibroblast-like synoviocytes (FLS). FLS were isolated from the synovium of knee osteoarthritis (OA) patients undergoing surgery. NDMVs, isolated from TNFα-stimulated healthy neutrophils, were characterized by electron microscopy and nanoparticle tracking analysis. MTT and scratch wound healing assays were used to measure FLS viability and migration after treatment with NDMVs, while internalization of fluorescently labeled NDMVs was appraised by flow cytometry and confocal microscopy. Levels of proinflammatory cytokines in supernatants were quantified by the Bio-Plex system. Incubation of FLS with NDMVs at a vesicle/cell ratio of 100 resulted in a time-dependent uptake, with 35% of synoviocytes containing microvesicles over a 6-24 h time period, with no significant change in cell viability. TNFα stimulated the cytokine expression in FLS, and NDMVs down-regulated TNFα-induced expression of IL-5, IL-6, IL-8, MCP-1, IFNγ and MIP-1ß. However, this down-regulation was selective, as NDMVs had no significant effects on TNFα-stimulated expression of IL-2 or IL-4. NDMVs were internalized by FLS to inhibit TNFα-stimulated broad-spectrum proinflammatory cytokine secretion. NDMVs, therefore, may exhibit an anti-inflammatory role in the regulation of the FLS function.

Carboxymethyl Cellulose Entrapped in a Poly(vinyl) Alcohol Network: Plant-Based Scaffolds for Cartilage Tissue Engineering.

Cartilage has a limited inherent healing capacity after injury, due to a lack of direct blood supply and low cell density. Tissue engineering in conjunction with biomaterials holds promise for generating cartilage substitutes that withstand stress in joints. A major challenge of tissue substitution is creating a functional framework to support cartilage tissue formation. Polyvinyl alcohol (PVA) was crosslinked with glutaraldehyde (GA), by varying the mole ratios of GA/PVA in the presence of different amounts of plant-derived carboxymethyl cellulose (CMC). Porous scaffolds were created by the freeze-drying technique. The goal of this study was to investigate how CMC incorporation and crosslinking density might affect scaffold pore formation, swelling behaviors, mechanical properties, and potential use for engineered cartilage. The peak at 1599 cm-1 of the C=O group in ATR-FTIR indicates the incorporation of CMC into the scaffold. The glass transition temperature (Tg) and Young's modulus were lower in the PVA/CMC scaffold, as compared to the PVA control scaffold. The addition of CMC modulates the pore architecture and increases the swelling ratio of scaffolds. The toxicity of the scaffolds and cell attachment were tested. The results suggest that PVA/CMC scaffolding material can be tailored in terms of its physical and swelling properties to potentially support cartilage formation.

The Effects of Andrographolide on the Enhancement of Chondrogenesis and Osteogenesis in Human Suprapatellar Fat Pad Derived Mesenchymal Stem Cells.

Andrographolide is a labdane diterpenoid herb, which is isolated from the leaves of Andrographis paniculata, and widely used for its potential medical properties. However, there are no reports on the effects of andrographolide on the human suprapatellar fat pad of osteoarthritis patients. In the present study, our goal was to evaluate the innovative effects of andrographolide on viability and Tri-lineage differentiation of human mesenchymal stem cells from suprapatellar fat pad tissues. The results revealed that andrographolide had no cytotoxic effects when the concentration was less than 12.5 µM. Interestingly, andrographolide had significantly enhanced, dose dependent, osteogenesis and chondrogenesis as evidenced by a significantly intensified stain for Alizarin Red S, Toluidine Blue and Alcian Blue. Moreover, andrographolide can upregulate the expression of genes related to osteogenic and chondrogenic differentiation, including Runx2, OPN, Sox9, and Aggrecan in mesenchymal stem cells from human suprapatellar fat pad tissues. In contrast, andrographolide suppressed adipogenic differentiation as evidenced by significantly diminished Oil Red O staining and expression levels for adipogenic-specific genes for PPAR-γ2 and LPL. These findings confirm that andrographolide can specifically enhance osteogenesis and chondrogenesis of mesenchymal stem cells from human suprapatellar fat pad tissues. It has potential as a therapeutic agent derived from natural sources for regenerative medicine.

No Difference in Pain After Spine Surgery with Local Wound Filtration of Morphine and Ketorolac: A Randomized Controlled Trial.

BACKGROUND: Controlling postoperative pain after spinal surgery is important for rehabilitation and patient satisfaction. Wound infiltration with local anesthetics may improve postoperative pain, but true multimodal approaches for achieving analgesia after spinal surgery remain unknown. QUESTIONS/PURPOSES: In this randomized, controlled, double-blind trial after lumbar interbody fusion, we asked: (1) Does multimodal analgesia reduce VAS pain scores by a clinically important amount? (2) Does this analgesic approach reduce the amount of morphine patients consume after surgery? (3) Is this approach associated with fewer opioid-related side effects after surgery? METHODS: This study included 80 adult patients undergoing lumbar interbody fusion who were randomized into two groups: A control group (n = 40) who received infiltration of the surgical incision at the end of the procedure with an injection of 0.5% bupivacaine 100 mg (20 mL) and epinephrine 0.5 mg (0.5 mL), and the multimodal group (n = 40), who received wound infiltration with the same approach but with different medications: 0.5% bupivacaine 92.5 mg (18.5 mL), ketorolac 30 mg (1 mL), morphine 5 mg (0.5 mL), and epinephrine 0.5 mg (0.5 mL). There were no between-group differences in the proportion of patients who were male, nor in the mean age, height, weight, preoperative pain score, or surgical time. All treatments were administered by one surgeon. All patients, the surgeon, and the researchers were blinded to the allocation of patients to each group. Pain at rest was recorded using the VAS. Postoperative morphine consumption (administered using a patient-controlled analgesia pump) and opiod-associated side effects including nausea/vomiting, pruritus, urinary retention, and respiratory depression were assessed; this study was analyzed according to intention-to-treat principles. No loss to follow-up or protocol deviations were noted. We considered a 2-cm change on a 10-cm scale on the VAS as the minimum clinically important difference (MCID). Differences smaller than this were considered unlikely to be important. RESULTS: At no point were there between-group differences in the VAS scores that exceeded the MCID, indicating no clinically important reductions in pain associated with administering multimodal injections. The highest treatment effect was observed at 3 hours that showed only a -1.3 cm mean difference between the multimodal and the control groups (3.2 ± 1.8 versus 4.5 ± 1.9 [95% CI -1.3 to -0.3]; p < 0.001), which was below the MCID. Morphine consumption was very slightly higher in the control group than in the multimodal group (2.8 ± 2.8 versus 0.3 ± 1.0, mean difference 2.47; p < 0.001). The percentage of patients reporting opioid-related side effects was lower in the multimodal group than in the control group. The proportions of nausea and vomiting were higher in the control group (30% [12 of 40] than in the multimodal group (3% [1 of 40]; p = 0.001). All of these side effects were transient and none was severe. CONCLUSIONS: Multimodal wound infiltration with an NSAID and morphine did not yield any clinically important reduction in pain or opioid consumption. Since no substantial benefit of adding these drugs to a patient's aftercare regimen was achieved, and considering the potential risks of administering opioids and NSAIDs (such as, polypharmacy in older patients, serious adverse effects of NSAIDs), we recommend against routine use of this approach in clinical practice. LEVEL OF EVIDENCE: Level I, therapeutic study.

Hepatic expression of HGF/C-met and native liver survival in biliary atresia.

BACKGROUND: The prognosis of biliary atresia (BA) remains difficult to predict. This study evaluated the roles of hepatocyte growth factor (HGF) and its receptor (C-met) towards clinical outcome and native liver survival. METHODS: Hepatic HGF and C-met expression were determined using immunohistochemistry from liver biopsies of 41 BA patients during Kasai operation, and 17 non-cholestatic patients. The HGF and C-met expression was visually scored as per its intensity and percentage of stained area. BA patients were classified as high- and low-HGF and C-met receptor status. Native liver survival was compared between the two groups at 3-year follow-up. Data are shown as median and range. MAIN RESULTS: Median age of BA patients was 2 (1-6) months. Hepatic HGF and C-met staining scores of BA patients were higher than those of non-cholestatic patients (P < 0.0001). There was a correlation between HGF and C-met staining scores (spearman r = 0.77, P < 0.0001). However, there was no association between their expression and early outcome at 6 months post-op. Mean follow-up time was 68.6 months. Survival analysis revealed that native liver survival at 1 year and 3 years were 88% and 77%, respectively. Additionally, 82.6% (19/23) of patients in the low-HGF group survived with native liver, compared with 66.7% (10/15) of those in high-HGF group (P = 0.436). For C-met expression, 78.6% (22/28) of low-score and 70% (7/10) of high score groups survived with native liver (P = 0.673). CONCLUSIONS: Strong expression of hepatic HGF and its receptor in BA patients was demonstrated. However, the expression was not associated with the early outcome and native liver survival. These results suggest that HGF involved in the liver pathology of BA but its expression cannot be used as a prognostic indicator. Small sample size of patients was a main limitation. Further studies are warranted to validate our findings.

Anatomical Differences Between Foot and Hand Web Space Reconstruction.

The differences in the anatomy of the foot and the hand may affect the dorsal flap design for web space reconstruction. In this study, the authors aimed to identify the differences in web space anatomy of the foot and the hand and provide a guideline of flap design for web space reconstruction in the foot and the hand. The right hands and right feet of adult volunteers were measured, including surgical landmarks (i.e., the dorsal prominence of proximal interphalangeal and metacarpophalangeal joints [or metatarsophalangeal joints]), proximal phalangeal length, tip of the web space, and width of web space. The web spaces and other parameters were analyzed and compared between the foot and the hand by using a paired t test with p < .05 to indicate statistical significance. A total of 108 web spaces of the foot and hand from 18 adult volunteers were analyzed. The parameters that were significantly different between the foot and the hand included (1) proximal phalangeal length (34.63 vs 60.16 mm), (2) average web height ratio (0.72 vs 0.51), (3) average web width ratio (0.69 vs 0.81), (4) mean slope angle (4.89° vs 19.26°), and (5) average abduction angle (25.33° vs 31.07°). In conclusion, the foot web space had a higher slope angle, less abduction angle, and shorter proximal phalangeal length. Therefore, the flap design for foot web space reconstruction requires a longer and narrower flap than the design for the hand. The recommended flap design length should be at least 72% of proximal phalangeal length for the foot versus 51% for the hand, and the width should be at least 69% of the distance between the tips of adjacent metatarsophalangeal joints for the foot versus 81% for the hand.

Relative telomere length and oxidative stress in musculoskeletal tumors.

Telomeres are capped at the end of the chromosome and gradually shorten when the cell divides. When there is an oxidative stress, it can cause the DNA to be damaged. Hence, 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been shown to be an indicator for oxidative DNA damage. This study aimed to determine the relative telomere length (RTL) and 8-OHdG levels in neoplastic tissues, adjacent non-neoplastic tissues, and blood leukocytes of musculoskeletal (MS) tumor patients. Neoplastic tissues were compared to adjacent non-neoplastic tissues in MS tumor patients (n = 46). Peripheral blood leukocytes (PBLs) of MS tumor subjects were compared to those of age-matched healthy controls (n = 107). RTL was evaluated by quantitative real-time polymerase chain reaction and 8-OHdG levels were quantified by enzyme-linked immunosorbent assay. The RTL in neoplastic tissues was significantly shorter than that in non-neoplastic tissues [1.12 (0.86-1.46) vs 1.45 (1.25-1.65), P = 0.001]. PBLs had lower RTL than non-neoplastic tissues in MS tumor patients [1.04 (0.85-1.13) vs 1.45 (1.25-1.65), P < 0.001]. However, there was no significant difference between RTL in PBLs and in neoplastic tissues. In addition, PBLs of MS tumor patients had higher RTL than those of the controls [1.04 (0.85-1.13) versus 0.78 (0.68-0.90), P < 0.001]. The 8-OHdG levels in neoplastic tissues were remarkably higher than those in non-neoplastic tissues [8.14 (6.81-11.37) nM/µg/µl vs. 3.79 (2.53-6.17) nM/µg/µl, P < 0.001]. Furthermore, plasma 8-OHdG levels in MS tumor patients were markedly greater than those in the controls [102.50 (73.16-133.50) nM vs. 41.09 (6.81-11.37) nM, P < 0.001]. Area under the curve (AUC) was 0.7536 (95% confident interval (CI) 0.6602-0.8469) when the cut-off value of RTL in PBLs was 0.97. Also, plasma 8-OHdG levels depicted that when the cut-off value was 38.67 nM, the AUC was 0.7723 (95% CI 0.6920-0.8527). Moreover, ROC curve analysis showed that both RTL and 8-OHdG appeared to improve the sensitivity (85.68%) and specificity (70.91%) with the AUC 0.8639 (95% CI 0.7500-0.9500). This study suggested that blood leukocyte RTL and plasma 8-OHdG could serve as promising non-invasive biomarkers to differentiate between MS tumor patients and healthy controls. Additionally, telomere attrition and increased oxidative DNA damage might play contributory roles in the pathogenesis of MS tumors.

Do-It-Yourself Microsuture from Human Hair for Basic Microsurgical Training.

BACKGROUND: Microsuture is an essential material for basic microsurgical training. However, it is consumable, expensive, and sometimes unavailable in the microsurgical laboratory. To solve this problem, we developed a microsuture made from human hair and needle gauge. METHODS: Do-It-Yourself (DIY) microsuture is made from human hair and needle gauge 32G (BD Ultra-Fine Pen Needles 4 mm × 32G). Methods are explained step by step. This DIY microsuture (labeled as "test microsuture") and nylon 8-0 (Ethilon suture 8-0, labeled as "standard microsuture") were used for teaching orthopaedic residents to perform arterial anastomosis in chicken thighs. All residents practiced without knowing that "test microsuture" was made from the DIY method. After completing the training, quality of both microsutures was evaluated by questionnaire in topics of (1) thread quality (size, strength, elasticity, handing, knot perform, and knot security), (2) needle quality (size, curve, shape, sharpness, handling, and strength), (3) needle-thread interface (size, strength, and smoothness), and (4) overall quality of microsuture. Each category was evaluated by Likert score (5 = excellent, 4 = good, 3 = fair, 2 = poor, and 1 = very poor). RESULTS: The DIY microsuture was performed in three steps: (1) insert human hair into needle gauge by microforceps, (2) bend needle into smooth curve, and (3) disconnect needle and create needle-hair interface. The questionnaire was completed by 30 orthopaedic residents and showed that thread quality of DIY and standard microsuture had "good" and "good-to-excellent" quality (mean Likert score: 3.77-4.23 and 3.80-4.27, respectively, with no statistical difference). Thread-needle interface quality of DIY and standard microsuture also had "good" and "good-to-excellent" quality (Likert score: 3.73-4.20 and 4.07-4.33, respectively, with no statistical difference). Needle part of DIY microsuture had lower quality than standard suture (fair-to-good compared with good-to-excellence quality, score 3.30-3.67 vs. 4.20-4.27, respectively, with a statistically significant difference, p-value < 0.05). However, overall quality of DIY suture and standard microsuture had "good" and "good-to-excellent" (mean Likert score: 3.73 and 4.00, respectively, with no statistical difference). CONCLUSION: The DIY microsuture from human hair and needle gauge could be an alternative for basic microsurgical training with lower cost, easy production, and more availability for use in practice with acceptable quality compared with that of standard microsuture.

Elevated serum leptin levels are associated with low vitamin D, sarcopenic obesity, poor muscle strength, and physical performance in knee osteoarthritis.

CONTEXT: The associations between serum leptin, vitamin D status, sarcopenic obesity, muscle strength and physical performance in osteoarthritis (OA) remain uncertain. OBJECTIVE: To analyse the relationships between serum leptin, vitamin D status, muscle strength and physical performance in OA patients. METHODS: A total of 208 knee OA patients were enrolled. Serum leptin, vitamin D, muscle strength and physical performance were evaluated. RESULTS: OA patients with sarcopenic obesity had significantly higher serum leptin levels than those with non-sarcopenic obesity. In addition, knee OA patients with sarcopenic obesity displayed low grip strength and poor physical performance. Furthermore, high serum leptin was negatively associated with vitamin D and physical performance. CONCLUSIONS: Serum leptin levels were correlated with low vitamin D, reduced muscle strength and functional impairment, suggesting that serum leptin might serve as a biomarker reflecting physical performance in OA patients.

Effect of vitamin E on oxidative stress level in blood, synovial fluid, and synovial tissue in severe knee osteoarthritis: a randomized controlled study.

BACKGROUND: This study was performed to evaluate the antioxidative and anti-inflammatory effects of vitamin E on oxidative stress in the plasma, synovial fluid, and synovial tissue of patients with knee osteoarthritis. METHODS: Seventy-two patients with late-stage knee osteoarthritis scheduled for total knee arthroplasty were randomized to take oral placebo (Group A) or 400 IU of vitamin E (Group B) once a day for 2 months before undergoing surgery. The blood levels of endpoints indicating oxidative stress or antioxidant capacity, Knee Society Score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC), and adverse effects were compared before and after the intervention between the two groups. At surgery, these redox endpoints and histological findings were compared between the synovial fluid and synovial tissue. RESULTS: In blood samples, the pre-intervention of oxidative stress and antioxidative capacity were not different between Group A and Group B. In post-intervention blood samples, the Malondialdehyde (Group A 1.34 ± 0.10, Group B 1.00 ± 0.09, p < 0.02), Alpha tocopherol (Group A 15.92 ± 1.08, Group B 24.65 ± 1.47, p < 0.01) and Trolox equivalent antioxidant capacity (Group A 4.22 ± 0.10, Group B 5.04 ± 0.10, 0 < 0.01) were significantly different between Group A and Group B. In synovial fluid samples, the Malondialdehyde (Group A 1.42 ± 0.12, Group B 1.06 ± 1.08, p 0.01), Alphatocopherol (Group A 4.51, Group B 7.03, p < 0.01), Trolox equivalent antioxidant capacity (Group A, 1.89 ± 0.06, Group B 2.19 ± 0.10) were significantly different between Group A and Group B. The pre-intervention WOMAC score and KSS score were not different between Group A and Group B. The post-intervention WOMAC score was significantly improved in all categories in Group B (Pain: Group A 27.26 ± 0.89, Group B 19.19 ± 1.43, p < 0.01; Stiffness: Group A 8.23 ± 0.79, Group B 5.45 ± 0.73, p 0.01; Function: Group A 94.77 ± 4.22, Group B 72.74 ± 6.55, p < 0.01). The post-intervention KSS score was significantly improved in all categories in Group B (Clinical: Group A 25.31 ± 14.33, Group B 33.52 ± 16.96, p < 0.01; Functional: Group A 41.43 ± 16.11, Group B 51.61 ± 19.60, p 0.02). Significantly fewer synovial tissue cells were stained with nitrotyrosine and hematoxylin-eosin in Group B than in Group A. There were no differences in adverse effects or surgical complications between the groups. CONCLUSION: Vitamin E is an effective antioxidant that can improve clinical symptoms and reduce oxidative stress conditions in patients with late-stage knee osteoarthritis. TRIAL REGISTRATION: This research project had been approved for registration at Thai Clinical Trials Registry (TCTR) since 2016-08-28 11:26:32 (Retrospective registered). The TCTR identification number is TCTR20160828001 .

Elevated serum heat shock protein 70 and liver stiffness reflect hepatic dysfunction and severity in postoperative biliary atresia.

BACKGROUND: Biliary atresia (BA) is a severe chronic liver disease characterized by progressive obstructive cholangiopathy of biliary tract. Heat shock protein 70 (HSP70) is involved in protecting cells against a wide variety of stress and plays a protective role in tissue damage. The purpose of this study was to investigate serum HSP70 and liver stiffness in BA and determine the association of serum HSP70, liver stiffness, and outcome parameters in post-Kasai BA patients. METHODS: One hundred post-Kasai BA patients and 40 controls were enrolled. Serum HSP70 levels were analyzed using enzyme-linked immunosorbent assay. Liver stiffness values were assessed by transient elastography. RESULTS: BA patients had significantly higher serum HSP70 and liver stiffness values than controls. Serum HSP70 and liver stiffness values were markedly elevated in BA patients with jaundice compared to those without jaundice (P < 0.001). Furthermore, serum HSP70 was more elevated in BA children with portal hypertension than those without portal hypertension (35.1 ± 2.1 vs. 27.9 ± 2.5 ng/mL, P < 0.001). Moreover, serum HSP70 was positively correlated with serum aspartate aminotransferase (r = 0.491, P < 0.001), alanine aminotransferase (r = 0.448, P < 0.001), total bilirubin (r = 0.303, P = 0.002), alkaline phosphatase (r = 0.414, P < 0.001), and liver stiffness values (r = 0.455, P < 0.001). There was a negative correlation between serum HSP70 and serum albumin (r = -0.434, P = 0.001). CONCLUSION: Serum HSP70 and liver stiffness values were higher in BA patients than controls. The increased serum HSP70 was correlated with hepatic dysfunction in BA. Consequently, serum HSP70 and liver stiffness could serve as non-invasive parameters reflecting the severity in post-Kasai BA.

Alteration of inflammatory cytokine production in primary total knee arthroplasty using antibiotic-loaded bone cement.

BACKGROUND: The aim was to compare serum levels of interleukin-6 (SIL6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and joint fluid IL-6 (JIL-6) level between total knee arthroplasty (TKA) that used bone cement (BC group) and antibiotic-loaded bone cement (ALBC group). MATERIALS AND METHODS: Thirty-nine patients (40 TKAs) with a mean age of 69.6 years were non-randomly assigned to the BC or ALBC groups. Samples of SIL6, ESR, and CRP were collected at baseline and at 24 h, 72 h, and 4 weeks after surgery. JIL-6 levels were collected intraoperatively before joint arthrotomy, before finishing the procedure and 24 h after surgery. Postoperative mediator levels were compared with baseline levels within the same group and between groups at each time point. Knee Society Score-knee (KSSK) and Knee Society Score-function (KSSF) scores were evaluated. RESULTS: SIL-6, ESR, and CRP levels were significantly elevated at 24 and 72 h, compared to baseline. Only SIL-6 levels at 72 h in the ALBC group showed a significantly lower level than those in the BC group. JIL-6 levels were not different between groups. There were no significant differences in KSSK or KSSF scores between groups at 4 weeks and the most recent follow-up (1.4 ± 0.6 years) evaluation. No correlations were identified among SIL-6 and JIL-6 levels at 24 and 72 h, and KSSK and KSSF scores at 4 weeks and at the most recent evaluation. CONCLUSIONS: ALBC showed a favorable immunomodulatory effect and lower SIL-6 level at 72 h following TKA compared to BC, although functional benefits require further investigation. LEVEL OF EVIDENCE: OCEBM, Level 3.

Plasma and synovial fluid inflammatory cytokine profiles in primary knee osteoarthritis.

OBJECTIVE: The objective of this study is to compare inflammatory cytokine levels in primary knee osteoarthritis (OA) patients and healthy controls. METHODS: A total of 32 knee OA patients and 14 healthy controls were enrolled. A multiplex immunoassay was utilized for 10 cytokines in plasma and synovial fluid. RESULTS: Plasma IL-2, IL-4, and IL-6 concentrations were significantly greater in knee OA patients than controls. Moreover, both plasma IL-4 and IL-6 were positively correlated with the radiographic severity of knee OA. CONCLUSIONS: Plasma IL-4 and IL-6 may serve as biomarkers reflecting the severity of OA.