Vitamin D reduces pain and cartilage destruction in knee osteoarthritis animals through inhibiting the matrix metalloprotease (MMPs) expression.

Aim of the study: In this study, we investigated the therapeutic potential of vitamin D (VITD) in OA Wistar rats induced by anterior cruciate ligament transection combined with medial meniscectomy (ACLT + MMx). In ACLT + MMx-induced OA rats, pain severity, cartilage destruction, inflammatory cytokines, and MMPs were all measured. Materials and methods: ACLT + MMx methods were used to induce OA, and pain behavioral studies such as the weight bearing test and paw withdrawal test were performed while the knee width and body weights were also measured. Furthermore, Hematoxylin and Eosin (H&E) staining was used to determine knee histopathological studies, as well as OARSI scoring, cartilage thickness, cartilage width, and cartilage degradation scores. The enzyme-linked immunosorbent assay (ELISA) studies were used to check the serum levels of VITD, C-telopeptide of Type II collagen (CTX-II), and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-10 (IL-10), and MMPs (MMP-3, MMP-9, and MMP-13). Finally, the reverse transcription polymerase chain reaction (RT-PCR) test was used to determine the levels of MMPs, nuclear factor-kappa B (NF-κB), TNF-α, IL-6, and IL-10 in IL-1ß stimulated chondrocytes. Results: The oral VITD supplement significantly reduced OA pain, inflammation, cartilage destruction, and MMPs levels. Furthermore, serum VITD levels increased while CTX-II levels decreased, indicating that VITD reduced cartilage degradation effectively. Moreover, VITD supplementation reduced the expression of pro-inflammatory TNF-α, IL-1ß, and IL-6 cytokines while increasing the expression of anti-inflammatory IL-10. The elevation of MMPs after ACLT + MMx surgery contributed to articular cartilage destruction, which was reduced by VITD supplementation. Finally, VITD supplementation significantly reduces serum levels of MMPs, IL-1ß, TNF-α, and IL-6 while increasing IL-10 levels. Then, using the in-vitro cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT assay, examine the cytotoxicity profile of VITD in rat chondrocytes after stimulated with IL-1ß, which shows no toxicity in the dose range of VITD 0-500 IU. Finally, RT-PCR studies in IL-1ß stimulated rat chondrocytes revealed that VITD (50, 100, and 500 IU) significantly reduced the mRNA levels of MMPs, NF-κB, TNF-α, and IL-6, while increasing IL-10 levels, indicating that VITD reduced chondrocyte destruction and overcame harsh conditions in a dose-dependent manner. Conclusion: Overall, the in vivo and in vitro findings show that VITD effectively reduces OA pain, inflammation, and chondrocyte destruction by lowering MMPs levels specifically.

Multimodal Analgesia With Extended-Release Dinalbuphine Sebacate for Perioperative Management: Expert Opinion and Consensus.

BACKGROUND: The insufficient treatment of postoperative pain is considered a major barrier to enhanced patient recovery following surgery. Opioids remain the standard therapy for postoperative pain; however, the epidemic crisis of opioid abuse in the US has resulted in opioid-sparing multimodal analgesia (MMA) strategies in anesthesia practice. Complete perioperative pain management, particularly after discharge, may be undermined, resulting in chronic postsurgical pain. Thus, anesthesiologists and pain physicians should provide comprehensive MMA guidance for perioperative pain management. METHODS: The Taiwan Pain Society organized a working group, which included experts in the field of anesthesia, pain, and surgery. This group performed an extensive literature search, quality review, and drafted a consensus, which was discussed by experts and edited for feedback. Recommendations covered consent instruction, treatment interventions, intramuscular injection techniques, and prophylaxis for postoperative adverse events. RESULTS: This consensus included (1) a comparison of the pharmacology and pharmacokinetics between nalbuphine and dinalbuphine sebacate, (2) recommendations to help clinicians establish MMA with extended-release dinalbuphine sebacate injection, and (3) management of common adverse events during the perioperative pain period. CONCLUSION: Extended-release dinalbuphine sebacate combined with the MMA strategy can reduce the medical burden and improve the quality of recovery following surgery.

Case Report: Successful Reversal of Residual Block with Sugammadex in a Patient Not Known to Have Myasthenia Gravis.

BACKGROUND Incomplete recovery from residual neuromuscular block agent (NMBA) after anesthesia is a serious adverse event in the post-anesthesia care unit. Acetylcholinesterase neostigmine is usually used to reverse residual neuromuscular blockade and facilitate spontaneous breathing and endotracheal extubation. CASE REPORT A 40-year-old woman received general anesthesia for strabismus correction surgery. At the end of surgery, repeated doses of neostigmine up to 85 µg/kg failed to reverse the residual neuromuscular blockade (train-of-four [TOF] ratio below 21%). Sugammadex (200 mg) provided immediate reversal, with the TOF ratio up to 100%. The patient regained spontaneous breathing, and the endotracheal tube was removed. After surgery, myasthenia gravis was diagnosed. CONCLUSIONS When unexpected prolonged neuromuscular blockade presents, the TOF ratio should be used to detect its depth and guide a reasonable dose of reversal agents. Anticholinesterase has a ceiling effect; once acetylcholinesterase activity is fully inhibited, administration of additional anticholinesterase can result in no further recovery. Furthermore, excessive acetylcholine can cause muscle weakness. In contrast, sugammadex is a selective reversal agent for steroidal NMBA, which works by encapsulation via tight water-soluble complexes with amino steroids (eg, rocuronium) rather than increasing acetylcholine at the neuromuscular junction. In this case, the recovery from moderate neuromuscular blockade by sugammadex was more effective and rapid than that by neostigmine. When refractory and prolonged residual neuromuscular blockade presents after repeated doses of anticholinesterase, sugammadex should be considered as an effective reversal agent. Particularly in cases of myasthenia gravis, sugammadex is superior to neostigmine for reversing rocuronium-induced NMBA in patients undergoing surgery.

Multimodal Analgesia with Extended-Release Dinalbuphine Sebacate for Perioperative Pain Management in Upper Extremity Trauma Surgery: A Retrospective Comparative Study.

INTRODUCTION: Patients undergoing upper extremity fracture surgery (UEFS) commonly suffer from unbearable acute pain. Opioids remain the mainstay of moderate to severe pain alleviation, although there is a growing concern regarding the increasing trend in misuse and abuse. This study aimed to observe the safety and efficacy of dinalbuphine sebacate (DS), a novel extended-release analgesic, along with multimodal analgesia (MMA) for post-UEFS pain control. METHODS: We retrospectively reviewed the records of patients undergoing UEFS between August 2020 and January 2021. Eligible patients were included and divided into two groups, depending on the analgesic regimen. In the DS group, 150 mg DS was administered intramuscularly at least 12 h pre-operatively, while in the conventional analgesia (CA) group, 40 mg parecoxib was given within 3 h before surgery. Intraoperative fentanyl administration was guided by the Analgesia Nociception Index System in both groups. For breakthrough pain, fentanyl was used as rescue medicine in the postanaesthesia care unit while tramadol and parecoxib were administered in the ward. RESULTS: Forty-nine patients were allocated to the DS group and 60 patients were allocated to the CA group. In comparison with the CA group, the proportion of patients requiring opioids for breakthrough pain post-operatively was significantly lower in the DS group (fentanyl: 31% vs. 68%, p < 0.001; tramadol: 27% vs. 70%, p < 0.001). The DS group also consumed lower amounts of post-operative rescue opioids. Furthermore, both mean worst and least pain scores were significantly lower in the DS group from post-operative day (POD) 1 to POD 5. There was no significant difference in intraoperative consumption of fentanyl or incidence of adverse events. CONCLUSION: This result suggests that extended-release DS is a suitable analgesic incorporated in MMA and a promising solution to the misuse and abuse of opioids.

Safe Practice of Total Intravenous Anesthesia With Target-Controlled Infusion in Taiwan: A Recommendation.

There have been immense advances in the safety and variety of intravenous anesthetic delivery systems including drug cost reduction, development of more effective opioids, and improvement in depth of anesthesia monitoring in the last 20 years. Propofol-based total intravenous anesthesia (TIVA) with target-controlled infusion (TCI) is relatively easy to practice. While this technique promotes a higher overall anesthesia quality and patient survival, especially for cancer patients, there are deficiencies in training and education of the technique. Therefore, the Society for Intravenous Anesthesia and the Association of Anesthetists (United Kingdom) have laid out guidelines in an attempt to highlight multiple important TIVA-related safety issues to help clinicians feel more confident. In the present article, we discuss five recommendations and four special clinical situations. Preparation, equipment familiarity, and safe delivery techniques are extremely important for the proper employment of this method. Herein, we emphasize the importance of proper education, and the clinical practice experience of the TIVA technique. Additionally, we suggest a modified connection method to set up a safely administered line. We highlight the advantages of using processed electroencephalogram monitoring (such as bispectral index or Entropy) to prevent awareness during TIVA administration in difficult clinical situations. These situations may include triple low patients (e.g., low blood pressure, low maintained effect-site concentration of propofol, and low body weight ≤ 18), obese patients, and patients with difficult infusion site monitoring or use of neuromuscular blocking agents. Due to a limited consensus among Taiwanese medical professionals, this document is intended to act as a safe practice reference for the use of TIVA with TCI. Additionally, two pithy formula codes, 4321 for propofol with fentanyl/alfentanil and 42222111 for propofol with remifentanil, are provided for the general population and one pithy formula code, 4321 for propofol with fentanyl, is provided for pediatric patients.

Detection and Evaluation of Serological Biomarkers to Predict Osteoarthritis in Anterior Cruciate Ligament Transection Combined Medial Meniscectomy Rat Model.

Biomarkers are essential tools in osteoarthritis (OA) research, clinical trials, and drug development. Detecting and evaluating biomarkers in OA research can open new avenues for researching and developing new therapeutics. In the present report, we have explored the serological detection of various osteoarthritis-related biomarkers in the preclinical model of OA. In this surgical OA model, we disrupted the medial tibial cartilage's integrity via anterior cruciate ligament transection combined with medial meniscectomy (ACLT+MMx) of a single joint of Wistar rats. The progression of OA was verified, as shown by the microscopic deterioration of cartilage and the increasing cartilage degeneration scoring from 4 to 12 weeks postsurgery. The concentration of serological biomarkers was measured at two timepoints, along with the complete blood count and bone electrolytes, with biochemical analysis further conducted. The panel evaluated inflammatory biomarkers, bone/cartilage biomarkers, and lipid metabolic pathway biomarkers. In chronic OA rats, we found a significant reduction of total vitamin D3 and C-telopeptide fragments of type II (CTX-II) levels in the serum as compared to sham-operated rats. In contrast, the serological levels of adiponectin, leptin, and matrix metallopeptidase (MMP3) were significantly enhanced in chronic OA rats. The inflammatory markers, blood cell composition, and biochemical profile remained unchanged after surgery. In conclusion, we found that a preclinical model of single-joint OA with significant deterioration of the cartilage can lead to serological changes to the cartilage and metabolic-related biomarkers without alteration of the systemic blood and biochemical profile. Thus, this biomarker profile provides a new tool for diagnostic/therapeutic assessment in OA scientific research.

Multimodal Analgesia With Long-Acting Dinalbuphine Sebacate Plus Transversus Abdominis Plane Block for Perioperative Pain Management in Bariatric Surgery: A Case Report.

Laparoscopic bariatric surgery is increasingly performed in morbidly obese patients. However, post-surgical pain is common and is usually managed with classical opioids such as morphine and fentanyl. Further, morbidly obese patients are predisposed to opioid-related side effects, especially post-operative nausea and vomiting (PONV), and respiratory depression. Obstructive sleep apnea in morbidly obese patients even predisposes them to respiratory depression. Thus, reducing opioid consumption is important. Multimodal analgesia (MMA) provides optimal perioperative analgesia while minimizing opioid consumption. Studies have shown that MMA strategy can provide sufficient pain relief in bariatric surgery with enhanced recovery. There are very few reports on the use of dinalbuphine sebacate (DS), a newly introduced non-controlled opioid medication with long-lasting analgesic effects. DS has a different mechanism of action from that of morphine or fentanyl and is non-addictive, with minimal side effects. It has been successfully used in laparoscopic cholecystectomy in our previous study. We present a case of a new MMA protocol with DS on a 46-year-old morbidly obese female patient who underwent laparoscopic sleeve gastrectomy. The MMA protocol included ultrasound-guided intramuscular DS injection plus transversus abdominis plane (TAP) block and other analgesics; it achieved good perioperative analgesia with opioid-sparing effect and enhanced patient's recovery with no pain in the following 4 months.

Transcriptome Analysis Reveals Novel Genes Associated with Cartilage Degeneration in Posttraumatic Osteoarthritis Progression.

OBJECTIVE: The current therapeutic strategy for posttraumatic osteoarthritis (PTOA) focuses on early intervention to attenuate disease progression, preserve joint function, and defer joint replacement timing. Sequential transcriptomic changes of articular cartilage in a rat model were investigated to explore the molecular mechanism in early PTOA progression. DESIGN: Anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx)-induced PTOA model was applied on male Wistar rats. Articular cartilages were harvested at time 0 (naïve), 2 week, and 4 weeks after surgery. Affymetrix Rat genome 230 2.0 array was utilized to analyze the gene expression changes of articular cartilages. RESULTS: We identified 849 differentially expressed genes (DEGs) at 2 weeks and 223 DEGs at 4 weeks post-ACLT + MMx surgery compared with time 0 (naïve group). Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to gain further insights from these DEGs. 22 novel genes and 1 novel KEGG pathway (axon guidance) in cartilage degeneration of osteoarthritis were identified. Axon guidance molecules-Gnai1, Sema4d, Plxnb1, and Srgap2 commonly dysregulated in PTOA progression. Gnai1 gene showed a concordant change in protein expression by immunohistochemistry staining. CONCLUSIONS: Our study identified 22 novel dysregulated genes and axon guidance pathway associated with articular cartilage degeneration in PTOA progression. These findings provide the potential candidates of biomarkers and therapeutic targets for further investigation.

In Vitro Differentiation of Human Placenta-Derived Multipotent Cells into Schwann-Like Cells.

Human placenta-derived multipotent stem cells (PDMCs) resembling embryonic stem cells can differentiate into three germ layer cells, including ectodermal lineage cells, such as neurons, astrocytes, and oligodendrocytes. The favorable characteristics of noninvasive cell harvesting include fewer ethical, religious, and legal considerations as well as accessible and limitless supply. Thus, PDMCs are attractive for cell-based therapy. The Schwann cell (SC) is the most common cell type used for tissue engineering such as nerve regeneration. However, the differentiation potential of human PDMCs into SCs has not been demonstrated until now. In this study, we evaluated the potential of PDMCs to differentiate into SC-like cells in a differentiation medium. After induction, PDMCs not only exhibited typical SC spindle-shaped morphology but also expressed SC markers, including S100, GFAP, p75, MBP, and Sox 10, as revealed by immunocytochemistry. Moreover, a reverse transcription-quantitative polymerase chain reaction analysis revealed the elevated gene expression of S100, GFAP, p75, MBP, Sox-10, and Krox-20 after SC induction. A neuroblastoma cell line, SH-SY5Y, was cultured in the conditioned medium (CM) collected from PDMC-differentiated SCs. The growth rate of the SH-SY5Y increased in the CM, indicating the function of PDMC-induced SCs. In conclusion, human PDMCs can be differentiated into SC-like cells and thus are an attractive alternative to SCs for cell-based therapy in the future.

Comparison of Anesthesia-Controlled Operating Room Time Between Propofol-Based Total Intravenous Anesthesia and Desflurane Anesthesia in Open Liver Resection: A Retrospective Study.

BACKGROUND: Reducing anesthesia-controlled time (ACT) such as extubation time may improve operation room (OR) efficiency result from different anesthetic techniques. However, the information about the difference in ACT between desflurane (DES) anesthesia and propofol-based total intravenous anesthesia (TIVA) techniques for open liver resection under general anesthesia is not available in the literature. METHODS: This retrospective study uses our hospital database to analyze the ACT of open liver resection after either DES/fentanyl-based anesthesia or TIVA via target-controlled infusion (TCI) with fentanyl/propofol from January 2010 to December 2011. The various time intervals including waiting for anesthesia time, anesthesia time, surgical time, extubation time, exit from OR after extubation, total OR time, and post-anesthetic care unit stay time and percentage of prolonged extubation (≥ 15 minutes) were compared between the two anesthetic techniques. RESULTS: We included 143 hepatocellular carcinoma patients, with 82 patients receiving TIVA and 61 patients receiving DES. The extubation time was faster (10.1 ± 3.2 min vs. 11.8 ± 5.2 min; P = 0.03), and the incidence of prolonged extubation was lower (9.8% vs. 26.8%; P = 0.02) in the DES group than in the TIVA group. The factors contributed to prolonged extubation were age, sex, anesthetic technique, and anesthesia time. CONCLUSION: The DES anesthesia provided faster extubation time and lower incidence of prolonged extubation compared with propofol-based TIVA by TCI in elective open liver resection. Besides, older age, male, TIVA, and lengthy anesthesia time were factors affecting prolonged extubation.

Preoperative Administration of Extended-Release Dinalbuphine Sebacate Compares with Morphine for Post-Laparoscopic Cholecystectomy Pain Management: A Randomized Study.

PURPOSE: Perioperative pain management plays a critical role in the effort to promote enhanced recovery after surgery (ERAS). Pain is also the most concern for patients after laparoscopic cholecystectomy (LC). Naldebain (extended-release dinalbuphine sebacate, DS) is an oil-based formulation for intramuscular injection that has been designed for extended release and can be used for preoperative analgesia over a 7-day period. This study was aimed to compare the efficacy of DS injection with that of regular postoperative morphine administered when necessary for the management of post-laparoscopic cholecystectomy pain. PATIENTS AND METHODS: Forty-four patients scheduled for elective laparoscopic cholecystectomy were included in this prospective study. The patients were allocated randomly into two groups, with equal numbers receiving preoperative DS versus post-operative morphine. A total of 21 and 22 patients completed the study within the preoperative DS and post-operative morphine group, respectively. RESULTS: There were no statistically significant differences between two treatment groups with respect to length of surgery, anesthetics used during operation, or the average visual analog scale pain score in the post-operative anesthesia care unit (PACU), and at 4, 24, 48, and 72 hours post-procedure. Morphine was required only during the first postoperative day among those in the DS group. Safety was comparable in both DS and morphine groups. CONCLUSION: A single preoperative dose of DS provides sufficient analgesia along with a manageable safety profile and no interference with surgical anesthetics when compared to control cases that underwent surgery without preoperative DS treatment. This pilot study suggests that preoperative administration of DS is safe and may decrease the need for postoperative opioid use after laparoscopic cholecystectomy. REGISTRATION: ClinicalTrials.gov Identifier: NCT03713216.

Shea Nut Oil Extracts Enhance the Intra-Articular Sodium Hyaluronate Effectiveness on Surgically Induced OA Progression in Rats.

Osteoarthritis (OA) progression is associated with joint pain and stiffness. Intra-articular hyaluronic acid (IAHA) injection in knee OA restores the viscoelasticity of the joint and prevents cartilage damage. Shea nut oil extract (SNO) was shown to provide chondroprotection on surgically-induced OA progression in rats. Here we aim to examine IAHA injection supplemented with SNO diet for a synergetic evaluation on the disease progression in OA rats. We employed an anterior cruciate ligament transection plus medial meniscectomy-induced knee OA rat model with up to 12 weeks of sign/behavior observation (knee width, weight-bearing) and histological assessments of joint damage. We found both IAHA and SNO alone significantly attenuated histological changes of cartilage degeneration and synovial reactions in these knee OA rats. Nonetheless, oral SNO alone mitigated OA pain and inflammation while IAHA alone had no significant impact on the weight-bearing test and knee joint swelling. Moreover, with IAHA-treated rats fed with oral SNO diet, additional anti-inflammatory and anti-nociceptive effects were found, which further enhanced and maintained IAHA protection. Given the differential phenotype of oral SNO vs. IAHA, a regimen of IAHA coupled with SNO supplement provides a long-term effect of IAHA treatment. Taken together, the SNO supplement can be safely used as an adjuvant diet for chronic symptomatic relief of OA coupled with IAHA management.

Scope and Applications of Nanomedicines for the Management of Neuropathic Pain.

Neuropathic pain, resulting from the dysfunction of the peripheral and central nervous system, occurs in a variety of pathological conditions including trauma, diabetes, cancer, HIV, surgery, multiple sclerosis, ischemic attack, alcoholism, spinal cord damage, and many others. Despite the availability of various treatment strategies, the percentage of patients achieving adequate pain relief remains low. The clinical failure of most effective drugs is often not due to a lack of drug efficacy but due to the dose-limiting central nervous system (CNS) toxicity of the drugs that preclude dose escalation. There is a need for cross-disciplinary collaborations to meet these challenges. In this regard, the integration of nanotechnology with neuroscience is one of the most important fields. In recent years, promising preclinical research has been reported in this field. This review highlights the current challenges associated with conventional neuropathic pain treatments, the scope for nanomaterials in delivering drugs across the blood-brain barrier, and the state and prospects of nanomaterials for the management of neuropathic pain.

Statin use and the risk of renal cell carcinoma: national cohort study.

Statins are a therapeutic drug with reducing plasma cholesterol levels and have been linked with potential antitumor effects. However, epidemiological studies on statin use and renal cell carcinoma (RCC) risk have been inconsistent. This cohort study aimed to examine this association in an Asian population. We identified patients who filled initial prescriptions for statins in the inpatient and ambulatory care order files from Taiwan's National Health Insurance Research Database between January 1, 1998 and December 31, 2005 as the statin users cohort (n=14,067). The comparison cohort comprised of patients who had not taken any statin in the previous years prior to January 1, 1998 or had used statins for less than 28 cumulative defined daily doses between January 1, 1998 and December 31, 2005 (n=56 268). The outcome of interest was pathologically verified RCC occurred between January 1, 1999 and December 31, 2013. The Fine-Gray competing risk model was fitted to estimate HRs accompanying 95% CI. Patients with the use of statins had a significantly lower risk of RCC as compared with the non-users cohort, yielding an adjusted HR of 0.64 (95% CI, 0.38 to 0.87). Moreover, we found a significant inverse association between cumulative statin use and the risk of RCC. Further, the inverse association between statin use and risk of RCC was evident in both sexes. This population-based cohort study provides longitudinal evidence that the use of statins was associated with a reduced risk of RCC.

Propofol-based total intravenous anesthesia did not improve survival compared to desflurane anesthesia in breast cancer surgery.

BACKGROUND: Breast cancer is the most common cancer in women and several perioperative factors may account for tumor recurrence and metastasis. The anesthetic agents employed during cancer surgery might play a crucial role in cancer cell survival and patient outcomes. We conducted a retrospective cohort study to investigate the relationship between the type of anesthesia and overall survival in patients who underwent breast cancer surgery performed by one experienced surgeon. METHODS: All patients who underwent breast cancer surgery by an experienced surgeon between January 2006 and December 2010 were included in this study. Patients were separated into two groups according to the use of desflurane or propofol anesthesia during surgery. Locoregional recurrence and overall survival rates were assessed for the two groups (desflurane or propofol anesthesia). Univariable and multivariable Cox regression models and propensity score matching analyses were used to compare the hazard ratios for death and adjust for potential confounders (age, body mass index, American Society of Anesthesiologists physical status classification, TNM stage, neoadjuvant chemotherapy, Charlson Comorbidity Index, anesthesiologists, and functional status). RESULTS: Of the 976 breast cancer patients, 632 patients underwent breast cancer surgery with desflurane anesthesia, while 344 received propofol anesthesia. After propensity scoring, 592 patients remained in the desflurane group and 296 patients in the propofol group. The mortality rate was similar in the desflurane (38 deaths, 4%) and propofol (22 deaths, 4%; p = 0.812) groups in 5-year follow-up. The crude hazard ratio (HR) for all patients was 1.13 (95% confidence interval [CI] 0.67-1.92, p = 0.646). No significant difference in the locoregional recurrence or overall 5-year survival rates were found after breast surgery using desflurane or propofol anesthesia (p = 0.454). Propensity score-matched analyses demonstrated similar outcomes in both groups. Patients who received propofol anesthesia had a higher mortality rate than those who received desflurane anesthesia in the matched groups (7% vs 6%, respectively) without significant difference (p = 0.561). In the propensity score-matched analyses, univariable analysis showed an insignificant finding (HR = 1.23, 95% CI 0.72-2.11, p = 0.449). After adjustment for the time since the earliest included patient, the HR remained insignificant (HR = 1.23, 95% CI 0.70-2.16, p = 0.475). CONCLUSION: In our non-randomized retrospective analysis, neither propofol nor desflurane anesthesia for breast cancer surgery by an experienced surgeon can affect patient prognosis and survival. The influence of propofol anesthesia on breast cancer outcome requires further investigation.

Propofol-based total intravenous anaesthesia is associated with better survival than desflurane anaesthesia in hepatectomy for hepatocellular carcinoma: a retrospective cohort study.

BACKGROUND: Previous studies have shown that anaesthetic technique can affect outcomes of cancer surgery. We investigated the association between anaesthetic technique and patient outcomes after elective hepatectomy for hepatocellular carcinoma. METHODS: This was a retrospective single-centre cohort study of patients who received elective hepatectomy for hepatocellular carcinoma from January 2005 to December 2014. Patients were grouped according to propofol or desflurane anaesthesia. Kaplan-Meier analysis was performed and survival curves were constructed from the date of surgery to death. After propensity matching, univariable and multivariable Cox regression models were used to compare hazard ratios for death. Subgroup analyses were performed for tumour-node-metastasis staging and distant metastasis and local recurrence. RESULTS: A total of 492 patients (369 deaths, 75.0%) with desflurane anaesthesia and 452 (139 deaths, 30.8%) with propofol anaesthesia were eligible for analysis. After propensity matching, 335 patients remained in each group. In the matched analysis, propofol anaesthesia had a better survival with hazard ratio of 0.47 (95% confidence interval, 0.38-0.59; P<0.001). Subgroup analyses also showed significantly better survival in the absence of distant metastasis (hazard ratio, 0.47; 95% confidence interval, 0.37-0.60; P<0.001) or local recurrence (hazard ratio, 0.22; 95% confidence interval, 0.14-0.34; P<0.001) in the matched groups. CONCLUSIONS: Propofol anaesthesia was associated with better survival in hepatocellular carcinoma patients who underwent hepatectomy. Prospective studies are warranted to evaluate the effects of propofol anaesthesia on surgical outcomes in hepatocellular carcinoma patients.

Oral shea nut oil triterpene concentrate supplement ameliorates pain and histological assessment of articular cartilage deterioration in an ACLT injured rat knee osteoarthritis model.

Osteoarthritis (OA) is a multifactorial joint disease and a common disabling condition in the elderly population. The associated pain and pathohistological changes in cartilage are common features of OA in both humans and animal models. Shea nut oil extract (SheaFlex75) contains a high triterpenoid concentration and has demonstrated anti-inflammatory and antiarthritic effects in both human and animal studies. In this study, we aim to investigate the potential of SheaFlex75 to prevent articular cartilage deterioration in a rat model of chronic OA progression. By employing anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx)-induced OA, we found attenuation of both early and chronic onset OA pain and cartilage degeneration in ACLT+MMx rats receiving SheaFlex75 dietary supplementation. Under long-term oral administration, the rats with induced OA presented sustained protection of both pain and OA cartilage integrity compared to the OA-control rats. Moreover, rats subjected to long-term SheaFlex75 ingestion showed normal biochemical profiles (AST, BUN and total cholesterol) and presented relatively lower triglycerides (TGs) and body weights than the OA-control rats, which suggested the safety of prolonged use of this oil extract. Based on the present evidence, preventive management is advised to delay/prevent onset and progression in OA patients. Therefore, we suggest that SheaFlex75 may be an effective management strategy for symptom relief and cartilage protection in patients with both acute and chronic OA.

Effects of intraoperative propofol-based total intravenous anesthesia on postoperative pain in spine surgery: Comparison with desflurane anesthesia - a randomised trial.

BACKGROUND: As reported, patients experience less postoperative pain after propofol-based total intravenous anesthesia (TIVA). In the present study, we investigated the postoperative analgesic effects between propofol-based TIVA and desflurane anesthesia after spine surgery. METHODS: Sixty patients were included who received (surgical time >180 minutes) lumbar spine surgery. Patients were randomly assigned to receive either TIVA (with target-controlled infusion) with propofol/fentanyl-based anesthesia (TIVA group) or desflurane/fentanyl-based anesthesia (DES group), titrated to maintain Bispectral Index values between 45 and 55. All patients received patient-controlled analgesia (PCA) with fentanyl for postoperative pain relief. Numeric pain rating scale (NRS) pain scores, postoperative fentanyl consumption, postoperative rescue tramadol use, and fentanyl-related side effects were recorded. RESULTS: The TIVA group patients reported lower NRS pain scores during coughing on postoperative day 1 but not day 2 and 3 (P = .002, P = .133, P = .161, respectively). Less fentanyl consumption was observed on postoperative days 1 and 2, but not on day 3 (375 µg vs 485 µg, P = .032, 414 µg vs 572 µg, P = .033, and 421 µg vs 479 µg, P = .209, respectively), less cumulative fentanyl consumption at postoperative 48 hours (790 µg vs 1057 µg, P = .004) and 72 hours (1210 µg vs 1536 µg, P = .004), and total fentanyl consumption (1393 µg vs 1704 µg, P = .007) when compared with the DES group. No difference was found in rescue tramadol use and fentanyl-related side effects. CONCLUSION: Patients anesthetized with propofol-based TIVA reported less pain during coughing and consumed less daily and total PCA fentanyl after lumbar spine surgery.

Magnesium sulfate inhibits binding of lipopolysaccharide to THP-1 cells by reducing expression of cluster of differentiation 14.

We investigated effects of magnesium sulfate (MgSO4) on modulating lipopolysaccharide (LPS)-macrophage binding and cluster of differentiation 14 (CD14) expression. Flow cytometry data revealed that the mean levels of LPS-macrophage binding and membrane-bound CD14 expression (mCD14) in differentiated THP-1 cells (a human monocytic cell line) treated with LPS plus MgSO4 (the LPS + M group) decreased by 28.2% and 25.3% compared with those THP-1 cells treated with LPS only (the LPS group) (P < 0.001 and P = 0.037), indicating that MgSO4 significantly inhibits LPS-macrophage binding and mCD14 expression. Notably, these effects of MgSO4 were counteracted by L-type calcium channel activation. Moreover, the mean level of soluble CD14 (sCD14; proteolytic cleavage product of CD14) in the LPS + M group was 25.6% higher than in the LPS group (P < 0.001), indicating that MgSO4 significantly enhances CD14 proteolytic cleavage. Of note, serine protease inhibition mitigated effects of MgSO4 on both decreasing mCD14 and increasing sCD14. In conclusion, MgSO4 inhibits LPS-macrophage binding through reducing CD14 expression. The mechanisms may involve antagonizing L-type calcium channels and activating serine proteases.

Manganese Oxide Nanozymes Ameliorate Mechanical Allodynia in a Rat Model of Partial Sciatic Nerve-Transection Induced Neuropathic Pain.

BACKGROUND: Reactive oxygen species (ROS) induced oxidative stress is linked to numerous neurological diseases, including neuropathic pain. Natural ROS scavenging enzymes like superoxide dismutase (SOD) and catalase have been found to be efficient in alleviating neuropathic pain. However, their sensitivity towards extreme pH and a short half-life limit their efficacy in vivo. Manganese oxide nanoparticles (MONPs) are recently known to possess ROS scavenging properties. In this study, MONPs were examined for their therapeutic effect on neuropathic pain. METHODS: The MONPs were synthesized by a hydrothermal method. The synthesized MONPs were characterized by UV/Vis, TEM, SEM, FTIR, NTA and XRD. The biocompatibility of the nanoparticles is evaluated in neural cells using LDH assay. MONPs were evaluated for their antioxidant activity by DPPH assay. In addition, in vitro ROS scavenging properties were examined in bone marrow-derived macrophage (BMDM) cells using 2',7'-dichlorofluorescin diacetate (DCFDA) assay. To evaluate the in vivo efficacy of nanoparticles, neuropathic pain was induced in Wistar rats by partial sciatic nerve transection (PSNT). On post-transection days 14 to 18, rats were intrathecally injected with MONPs and paw withdrawal threshold was measured. The spinal cords were collected and processed for Western blotting and histological analysis. RESULTS: The synthesized MONPs were biocompatible and showed effective antioxidant activity against DPPH free radical scavenging. Further, the nanoparticles scavenged ROS efficiently in vitro in BMDM and their intrathecal administration significantly reduced mechanical allodynia as well as the expression of cyclooxygenase-2 (COX-2), an important mediator of chronic and inflammatory pain in the spinal dorsal horns of PSNT rats. CONCLUSION: As ROS play a significant role in neuropathic pain, we expect that MONPs could be a promising tool for the treatment of various inflammatory diseases and might also serve as a potential nanocarrier for the delivery of analgesics.