Cervical Disc Arthroplasty (CDA) versus Anterior Cervical Discectomy and Fusion (ACDF) for Two-Level Cervical Disc Degenerative Disease: An Updated Systematic Review and Meta-Analysis.

Background: Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are both considered to be efficacious surgical procedures for treating cervical spondylosis in patients with or without compression myelopathy. This updated systematic review and meta-analysis aimed to compare the outcomes of these procedures for the treatment of cervical degenerative disc disease (DDD) at two contiguous levels. Methods: The PubMed, EMBASE, and Cochrane CENTRAL databases were searched up to 1 May 2023. Studies comparing the outcomes between CDA and ACDF in patients with two-level cervical DDD were eligible for inclusion. Primary outcomes were surgical success rates and secondary surgery rates. Secondary outcomes were scores on the Neck Disability Index (NDI) and Visual Analogue Scale (VAS) for neck and arm pain, as well as the Japanese Orthopaedic Association (JOA) score for the severity of cervical compression myelopathy and complication rates. Results: In total, eight studies (two RCTs, four retrospective studies, and two prospective studies) with a total of 1155 patients (CDA: 598; ACDF: 557) were included. Pooled results revealed that CDA was associated with a significantly higher overall success rate (OR, 2.710, 95% CI: 1.949-3.770) and lower secondary surgery rate (OR, 0.254, 95% CI: 0.169-0.382) compared to ACDF. In addition, complication rates were significantly lower in the CDA group than in the ACDF group (OR, 0.548, 95% CI: 0.326 to 0.919). CDA was also associated with significantly greater improvements in neck pain VAS than ACDF. No significant differences were found in improvements in the arm VAS, NDI, and JOA scores between the two procedures. Conclusions: CDA may provide better postoperative outcomes for surgical success, secondary surgery, pain reduction, and postoperative complications than ACDF for treating patients with two-level cervical DDD.

Patent blue versus methylene blue and indigo carmine as a better dye for chromodiscography: in vitro staining efficacy and cytotoxicity study using bovine coccygeal intervertebral discs.

BACKGROUND CONTEXT: Chromodiscography is an integral part of full-endoscopic discectomy (FED), comprising ordinary discography with radiopacity produced by contrast medium and intradiscal stain for visualizing annular defects in the endoscopic field. Nevertheless, concerns remain about the cytotoxicity of the stains used. The study of their staining efficacy is also lacking. PURPOSE: To evaluate the feasibility of methylene blue, patent blue, and indigo carmine for intradiscal injection, investigate the effectiveness of each dye, and define critical concentration with adequate staining efficacy and tolerable cytotoxicity for use in chromodiscography during FED. STUDY DESIGN: An experimental in vitro study. METHODS: Dye stock solutions were prepared from powder. The stock was diluted with culture medium or balanced saline and used for cytotoxicity or intervertebral disc staining assays, respectively. Bovine tails were obtained from the local slaughterhouse and functional spine units of intervertebral discs were acquired by transverse incision at the disc level. Each disc was punctured over the posterolateral aspect using a surgical knife to simulate an annular defect. The intradiscal injection was performed with each dye at different concentrations using a 22G needle from the contralateral aspect of the punctured site. Staining efficacy was quantified using ImageJ software. Primary cells of bovine tails were cultivated in each dye at different concentrations. Cytotoxicity was assessed 24 hours after stain exposure using the CCK-8 toxicity assay. RESULTS: Staining efficacy and cytotoxicity were proportional to the concentration of tested dyes. Lower limits of concentration producing significant staining efficacy of indigo carmine, methylene blue, and patent blue were 0.25 mg/mL, 0.25 mg/mL, and 0.05 mg/mL, respectively. Compared with controls, concentrations showing significant toxicity for indigo carmine, methylene blue, and patient blue were 1 mg/mL, 0.5 mg/mL, and 2.5 mg/mL, respectively. CONCLUSIONS: Patent blue can serve as a more suitable tissue stain than either indigo carmine or methylene blue due to the widest range of tradeoff concentration within 0.05 to 2.5 mg/mL. CLINICAL SIGNIFICANCE: Patent blue with the characteristic of good staining efficacy and lower cytotoxicity may be a promising option for chromodiscography during FED.

Clinical Efficacy of Polycaprolactone ß-Calcium Triphosphate Composite for Osteoconduction in Rabbit Bone Defect Model.

The combination of ß-tricalcium phosphate (ß-TCP) with polycaprolactone (PCL) has been considered a promising strategy for designing scaffolds for bone grafting. This study incorporated PCL with commercially available ß-TCP (OsteoceraTM) to fabricate an injectable bone substitute and evaluate the effect of PCL on compressive strength and setting time of the hydraulic cement. The mechanical testing was compliant with the ASTM D695 and ASTM C191-13 standards. Results showed that PCL-TCP composite presented a well-defined architecture with uniform pore distribution and a significant increase in compressive strength compared with ß-TCP alone. Eighteen rabbits, each with two surgically created bone defects, were treated using the PCL-TCP composites. The composite materials were resorbed and replaced by newly formed bone tissue. Both PCL-TCP and ß-TCP demonstrated equivalent clinical effects on osteoconduction property in terms of the percentage of newly formed bone area measured by histomorphometric analysis. PCL-TCP was proven to be as effective as the commercially available ß-TCP scaffold (OsteoceraTM).

Cytotoxic triterpenoids from the root bark of Helicteres angustifolia.

Three new triterpenoids, 3beta-acetoxy-27-[(E)-cinnamoyloxy]lup-20(29)-en-28-oic acid methyl ester (1), 3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]lup-20(29)-en-28-oic acid (2), and 3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl ester (3), together with nine known triterpenoids, 4-12, were isolated from the root bark of Helicteres angustifolia. The structures of these compounds were established on the basis of spectroscopic methods including 2D-NMR experiments. All twelve compounds were tested for their cytotoxic activities against human colorectal cancer (COLO 205), human hepatoma (Hep G2), and human gastric cancer (AGS) cell lines in vitro. Among them, compounds 2, 3, 3beta-O-[(E)-coumaroyl]betulinic acid (6), and pyracrenic acid (7) showed significant cytotoxic activities against human cancer cells COLO 205 and AGS.

Oleanane-type triterpenes from the flowers, pith, leaves, and fruit of Tetrapanax papyriferus.

Four oleanane-type triterpenes, 3alpha,21beta,22alpha-trihydroxy-11,13(18)-oleanadien-28-oic acid (1), 3-epi-papyriogenin C (2), 21-O-acetyl-21-hydroxy-3-oxo-11,13(18)-oleanadien-28-oic acid (3) and 3beta-hydroxy-21-oxo-11,13(18)-oleanadien-28-oic acid methyl ester (4), together with four known triterpenes, were isolated from Tetrapanax papyriferus (Hook) K. Koch. Papyriogenin A (8) exhibited anti-HIV activity and low cytotoxicity in acutely infected H9 lymphocytes. Their structures were determined by analysis of spectroscopic data, including by 1D and 2D NMR.

Spontaneous rupture of the patellar and contralateral quadriceps tendons associated with secondary hyperparathyroidism in a patient receiving long-term dialysis.

Although spontaneous rupture of the extensor tendon of the knee is more likely to occur in uremic patients with secondary hyperparathyroidism, simultaneous ruptures of bilateral knee extensor tendons is a rarely reported condition. We describe a 30-year-old man with uremia who underwent subtotal parathyroidectomy because of secondary hyperparathyroidism with very high serum parathyroid hormone (PTH) level (1940.4 pg/mL). Two weeks later, he complained of a sharp pain in both knees without trauma when he walked downstairs with his left knee forward and right knee behind. Spontaneous simultaneous ruptures of the right patellar tendon and the left quadriceps tendon were diagnosed and surgically repaired. The mechanism of spontaneous tendon rupture in uremic patients with secondary hyperparathyroidism seems to be related to high PTH level which results in osteolytic bone resorption at the tendon insertion site. Early surgical repair, control of secondary hyperparathyroidism, early use of vitamin D analogs, and total parathyroidectomy with or without autotransplantation of part of the parathyroid gland, can treat and prevent tendon rupture or re-rupture with satisfactory results.

Substance P Receptor Antagonist Suppresses Inflammatory Cytokine Expression in Human Disc Cells.

STUDY DESIGN: Laboratory study. OBJECTIVE: To evaluate whether blockade of the Substance P (SP) NK1R attenuates its proinflammatory effect on human intervertebral disc cells (IVD), and to evaluate the signaling pathways associated with SP. SUMMARY OF BACKGROUND DATA: SP and its receptors are expressed in human IVD cells, and cause upregulation of inflammatory mediators; however, the effects of blocking these receptors have not been studied in human IVD cells. METHODS: Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were expanded in monolayer, and then suspended in alginate beads. The alginate beads were treated with culture medium first containing a high affinity NK1R antagonist (L-760735) at different concentrations, and then with medium containing both NK1R antagonist and SP at 2 concentrations. Ribonucleic acid was isolated and transcribed into cDNA. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to evaluate expression of interleukin (IL)-1ß, IL-6, and IL-8. Western blot analysis was performed to examine levels of the phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB p65). The cells were pretreated with specific inhibitors of p38 (SB203580), ERK1/2 (PD98059), and p65 (SM7368) and then stimulated with SP. RESULTS: We detected expression of NK1R, neurokinin receptor 2 (NK2R), and neurokinin receptor 3 (NK3R) in AF and NP cells. Treatment of disc cells with the NK1R antagonist was able to suppress expression of IL-1ß, IL-6, and IL-8 in a dose-dependent manner. SP stimulation increased phosphorylation of p38-MAPK and ERK1/2, but not of NFκB p65. This indicates that p38-MAPK and ERK1/2 control SP-induced cytokine expression independently from NF-kB p65. Inhibition of p38 and ERK1/2 activation reduced SP-induced IL-6 production in human disc cells. CONCLUSION: NK1R is responsible for the proinflammatory effect of SP on IVD cells and this effect can be blocked by preventing binding of SP to NK1R. This study shows for the first time that SP mediates signaling in disc cells through NK1R and that SP activates the proinflammatory p38-MAPK and ERK1/2 pathways. LEVEL OF EVIDENCE: 4.

Flavonoids from the aquatic plant Eriocaulon buergerianum.

Four flavonoids including (2S)-3',4'-methylenedioxy-5,7-dimethoxyflavan and hispidulin 7-(6-E-p-coumaroyl-beta-D-glucopyranoside), and one tocopherol were isolated from the capitulum of Eriocaulon buergerianum KOERN. Their structures were established by spectral and chemical evidence.

Withangulatin I, a new cytotoxic withanolide from Physalis angulata.

A new withanolide, withangulatin I (2), was isolated from the whole plant of Physalis angulata. Its structure was established as (20S,22R)-15alpha-acetoxy-5beta,6beta-epoxy-14alpha-hydroxy-1,4-dioxo-witha-2,16,24-trienolide on the basis of chemical and spectroscopic methods including 2D-NMR and circular dichroism (CD) experiments. Withangulatin A (1) and withangulatin I (2) were tested for their cytotoxic activities against two human cancer cell lines, colorectal carcinoma COLO 205 and gastric carcinoma AGS, in vitro. Compounds 1 and 2 exhibited inhibitory activities against these two human cancer cells with IC(50) values of 16.6 and 1.8 and 53.6 and 65.4 muM, respectively.

Cerebrosides and tocopherol trimers from the seeds of Euryale ferox.

Two new cerebrosides, ferocerebrosides A (1) [(2S,3R,4E,8E,2'R)-1-O-(beta-glucopyranosyl)-N-(2'-hydroxydocosanoyl)-4,8-sphingadienine] and B (2) [(2S,3R,4E,8E,2'R)-1-O-(beta-glucopyranosyl)-N-(2'-hydroxytetracosanoyl)-4,8-sphingadienine], two new tocopherol trimers, ferotocotrimers C (5) and D (6), and two known tocopherol trimers, IVb (3) and IVa (4), were isolated from the seeds of Euryale ferox. Their structures were determined on the basis of spectroscopic data, especially 1D and 2D NMR experiments. Compounds 1 and 2 showed cytotoxicity in the brine shrimp lethality bioassay, with LC50 values of 0.17 and 0.20 mM, respectively.

Cucurbitacin B 2-sulfate and cucurbitacin glucosides from the root bark of Helicteres angustifolia.

A new sulfated cucurbitacin, cucurbitacin B 2-sulfate (1) and a new cucurbitacin glucoside, cucurbitacin G 2-O-beta-D-glucopyranoside (2) together with two known cucurbitacin glucosides, arvenin I and arvenin III were isolated from the root bark of Helicteres angustifolia. The structures of these compounds were established on the basis of spectroscopic and chemical evidence. These four compounds taste of strong bitterness. Compound 1 is a first sulfated cucurbitacin found in plants.

Dioscorin isolated from Dioscorea alata activates TLR4-signaling pathways and induces cytokine expression in macrophages.

The Toll-like receptor 4 (TLR4)-signaling pathway is crucial for activating both innate and adaptive immunity. TLR4 is a promising molecular target for immune-modulating drugs, and TLR4 agonists are of therapeutic potential for treating immune diseases and cancers. Several medicinal herb-derived components have recently been reported to act via TLR4-dependent pathways, suggesting that medicinal plants are potential resources for identifying TLR4 activators. We have applied a screening procedure to systematically identify herbal constituents that activate TLR4. To exclude possible LPS contamination in these plant-derived components, a LPS inhibitor, polymyxin B, was added during screening. One of the plant components we identified from the screening was dioscorin, the glycoprotein isolated from Dioscorea alata. It induced TLR4-downstream cytokine expression in bone marrow cells isolated from TLR4-functional C3H/HeN mice but not from TLR4-defective C3H/HeJ mice. Dioscorin also stimulated multiple signaling molecules (NF-kappaB, ERK, JNK, and p38) and induced the expression of cytokines (TNF-alpha, IL-1beta, and IL-6) in murine RAW 264.7 macrophages. Furthermore, the ERK, p38, JNK, and NF-kappaB-mediated pathways are all involved in dioscorin-mediated TNF-alpha production. In summary, our results demonstrate that dioscorin is a novel TLR4 activator and induces macrophage activation via typical TLR4-signaling pathways.

Flavonoids and benzene derivatives from the flowers and fruit of Tetrapanax papyriferus.

Two new flavonoids, kaempferol 7-O-(2-E-p-coumaroyl-alpha-l-rhamnoside) (1) and kaempferol 7-O-(2,3-di-E-p-coumaroyl-alpha-l-rhamnoside) (2), together with 10 known compounds were isolated from the flowers and fruit of Tetrapanax papyriferus. Compounds 1 and 2 showed cytotoxicity by brine shrimp lethality bioassay with LC(50) values of 0.57 and 0.40 mM, respectively.