A narrative review of endoscopic spine surgery: history, indications, uses, and future directions.

Background and Objective: The concept of endoscopic surgery began in the 1930s and has since undergone numerous advancements in both technology and surgical indications. Its main benefit is providing the opportunity to perform surgery while minimizing disruption to surrounding structures. The purpose of this review is to summarize the history, uses, and future directions for spine endoscopic surgery. Methods: A review of national databases was performing using key terms "endoscopic", "spine" and "surgery" for literature from 1900 to 2023. Studies that aimed to describe the utilities of endoscopic surgeries, associated outcomes, limitations, and future directions were included. Studies that were not in English were excluded. Key Content and Findings: This review includes a brief overview of the history of endoscopic surgery and its current two main approaches, transforaminal and interlaminar approaches. It then summarizes the main indications and utilization of endoscopic surgery in the lumbar, cervical and thoracic spine, as well as expansion in managing spine tumors, infections, and outpatient surgical cases. Conclusions: There are many rising indications and uses for endoscopic spine surgery in nearly every aspect of the spine. Compared to conventional spine surgery, there is early evidence showing endoscopic surgery is associated with less post-operative pain, shorter hospital stays, and possibly quicker recovery times. As current trends in spine surgery move towards minimally invasive techniques, it is anticipated that the use of endoscopic surgery will continue to expand.

Narrative review: erector spinae block in spine surgery.

Background: Lumbar spine surgery is an ever-increasing procedure with multiple analgesia techniques utilized for postoperative pain control. More recently, erector spinae plane (ESP) blocks have been used to limit the use of opioids after surgery. The authors aimed to review the current literature on ESP blocks and its potential use in the outpatient setting. Methods: Several randomized controlled trials were evaluated that compared erector spinae block to traditional anesthesia where the primary outcome of postoperative opioid use was assessed. Randomized control trials comparative studies were also evaluated to assess erector spinae block effect on outpatient procedures. Secondary outcomes include, postoperative pain, patient satisfaction, patient length of stay, and post-operative complications. Key Content and Findings: Erector spinae block was found in general to lower postoperative opioid use compared to traditional anesthesia. In addition, the authors found improved patient satisfaction and less postoperative pain in the erector spinae cohort. Post-operative complications were lower in the erector spinae block group compared to traditional anesthesia, especially in regards to vomiting and nausea. Conclusions: While these studies do possess their limitations due to the low number of randomized control studies on erector spinae block, early data does suggest that erector spinae block appears to be superior to that of traditional anesthesia for those undergoing spine surgery.

Comparison of treatment recompression tables for neurologic decompression illness in swine model.

BACKGROUND: Significant reductions in ambient pressure subject an individual to risk of decompression illness (DCI); with incidence up to 35 per 10,000 dives. In severe cases, the central nervous system is often compromised (>80%), making DCI among the most morbid of diving related injuries. While hyperbaric specialists suggest initiating recompression therapy with either a Treatment Table 6 (TT6) or 6A (TT6A), the optimal initial recompression treatment for severe DCI is unknown. METHODS: Swine were exposed to an insult dive breathing air at 7.06 ATA (715.35 kPa) for 24 min followed by rapid decompression at a rate of 1.82 ATA/min (184.41 kPa/min). Swine that developed neurologic DCI within 1 hour of surfacing were block randomized to one of four United States Navy Treatment Tables (USN TT): TT6, TT6A-air (21% oxygen, 79% nitrogen), TT6A-nitrox (50% oxygen, 50% nitrogen), and TT6A-heliox (50% oxygen, 50% helium). The primary outcome was the mean number of spinal cord lesions, which was analyzed following cord harvest 24 hours after successful recompression treatment. Secondary outcomes included spinal cord lesion incidence and gross neurologic outcomes based on a pre- and post- modified Tarlov assessment. We compared outcomes among these four groups and between the two treatment profiles (i.e. TT6 and TT6A). RESULTS: One-hundred and forty-one swine underwent the insult dive, with 61 swine meeting inclusion criteria (43%). We found no differences in baseline characteristics among the groups. We found no significant differences in functional neurologic outcomes (p = 0.77 and 0.33), spinal cord lesion incidence (p = 0.09 and 0.07), or spinal cord lesion area (p = 0.51 and 0.17) among the four treatment groups or between the two treatment profiles, respectively. While the trends were not statistically significant, animals treated with TT6 had the lowest rates of functional deficits and the fewest spinal cord lesions. Moreover, across all animals, functional neurologic deficit had strong correlation with lesion area pathology (Logistic Regression, p < 0.01, Somers' D = 0.74). CONCLUSIONS: TT6 performed as well as the other treatment tables and is the least resource intensive. TT6 is the most appropriate initial treatment for neurologic DCI in swine, among the tables that we compared.

The effect of posture on lumbar muscle morphometry from upright MRI.

PURPOSE: To assess the effect of upright, seated, and supine postures on lumbar muscle morphometry at multiple spinal levels and for multiple muscles. METHODS: Six asymptomatic volunteers were imaged (0.5 T upright open MRI) in 7 postures (standing, standing holding 8 kg, standing 45° flexion, seated 45° flexion, seated upright, seated 45° extension, and supine), with scans at L3/L4, L4/L5, and L5/S1. Muscle cross-sectional area (CSA) and muscle position with respect to the vertebral body centroid (radius and angle) were measured for the multifidus/erector spinae combined and psoas major muscles. RESULTS: Posture significantly affected the multifidus/erector spinae CSA with decreasing CSA from straight postures (standing and supine) to seated and flexed postures (up to 19%). Psoas major CSA significantly varied with vertebral level with opposite trends due to posture at L3/L4 (increasing CSA, up to 36%) and L5/S1 (decreasing CSA, up to 40%) with sitting/flexion. For both muscle groups, radius and angle followed similar trends with decreasing radius (up to 5%) and increasing angle (up to 12%) with seated/flexed postures. CSA and lumbar lordosis had some correlation (multifidus/erector spinae L4/L5 and L5/S1, r = 0.37-0.45; PS L3/L4 left, r = - 0.51). There was generally good repeatability (average ICC(3, 1): posture = 0.81, intra = 0.89, inter = 0.82). CONCLUSION: Changes in multifidus/erector spinae muscle CSA likely represent muscles stretching between upright and seated/flexed postures. For the psoas major, the differential level effect suggests that changing three-dimensional muscle morphometry with flexion is not uniform along the muscle length. The muscle and spinal level-dependent effects of posture and spinal curvature correlation, including muscle CSA and position, highlight considering measured muscle morphometry from different postures in spine models.

Racial disparities in late-stage prostate cancer: a SEER analysis 2005-2015.

INTRODUCTION: To evaluate the impact of prostate cancer screening guidelines on different racial and ethnic populations. MATERIALS AND METHODS: Data was collected from the 2005-2015 Surveillance, Epidemiology, and End Results (SEER) program. Incidence of prostate cancer diagnosis was categorized and analyzed by stage, race/ethnicity, and age group. Appropriate univariate and multivariable statistical analysis was performed. RESULTS: The odds of being diagnosed with regional-stage prostate cancer in 2013-2015 were 1.3 times higher for black men, 1.3 times higher for Asian American/Pacific Islander (AAPI) men, and 1.2 times higher for white men when compared to 2005-2008. The odds of being diagnosed with distant-stage prostate cancer in 2013-2015 were 1.6 times higher for black men, 1.8 times higher for AAPI men, and 2.1 times higher for white men when compared to 2005-2008. In 2005-2008, 2009-2012, and 2013-2015 respectively, the odds of being diagnosed with distant-stage prostate cancer were 1.8 times higher, 1.7 times higher, and 1.4 times higher for black men compared to white men, and 1.5 times higher, 1.5 times higher, and 1.4 times higher for AAPI men compared to white men (all respective p < .001). CONCLUSIONS: The proportion of late-stage prostate cancer has increased significantly in all US males regardless of race and/or ethnicity. From 2013-2015, all men had a higher chance of being diagnosed with regional or distant stage disease compared to years prior. Newly-diagnosed regional-stage disease increased the most over time in AAPI and black men, while distant prostate cancer increased the most over time in white men.

Bilateral cervical facet dislocations at two adjacent levels: A case report.

BACKGROUND: Cervical facet dislocations are rare in patients sustaining traumatic subaxial injuries. They occur due to hyperflexion-distraction and can occur unilaterally or bilaterally resulting in significant spinal instability. Bilateral facet dislocations at one level are less common than unilateral dislocations, while bilateral facet dislocations at adjacent spinal levels have only been reported twice in literature. CASE DESCRIPTION: A 31-year-old male presented with bilateral facet dislocations at two adjacent cervical levels (C6/C7 and C7/T1) following a fall from 40 to 50 feet. The patient had undergone a C6/C7 disk arthroplasty a few weeks before the traumatic event. CONCLUSION: Here, we present the unique case of cervical bilateral jumped facets occurring at two adjacent levels (i.e., C6-C7 and C7-T1). Notably, the antecedent cervical C6-C7 arthroplasty likely contributed to the altered load distribution, leading to this unusual instance of bilateral adjacent level facet dislocations. In such cases, surgical reduction and fixation may prove technically challenging warranting, therefore, careful preoperative planning.

The effects of tranylcypromine on osteoclastogenesis in vitro and in vivo.

Identification of anti-osteoclastogenic agents is important for the treatment of bone loss diseases that feature excessive osteoclast (OC) activity and bone resorption. Tranylcypromine (TCP), an irreversible inhibitor of monoamine oxidase (MAO), has been used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders. TCP has been discovered to exert anabolic effect on osteoblasts, and MAO-A has also been verified as an important mediator in prostate cancer cells to accelerate osteoclastogenesis. In current study, we were focused on TCP and MAO-A effects on osteoclastogenesis. As illustrated by tartrate-resistant acid phosphatase staining, TCP was capable of inhibiting osteoclastogenesis induced by receptor activators of the NF-κB ligand (RANKL) in bone marrow-derived macrophage cells without any cytotoxicity. It was also shown to effectively suppress bone resorption of OCs. The subsequent study revealed that TCP inhibited osteoclastogenesis-related genes in a time-dependent manner through protein kinase B (AKT)-mediated mechanism followed by the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)-c-fos pathway. And TCP could overcome the osteoclastogenic effects of AKT activator SC79. In addition, our results indicated that the expression and catalytic activity of MAO-A were up-regulated by RANKL stimulation and down-regulated by TCP in vitro and in vivo. Furthermore, the effects of MAO-A knockdown on OC differentiation indicated that MAO-A played an important role in osteoclastogenesis in vitro and might contribute to the inhibitory effects of TCP. And AKT, NFATc1, and c-fos were involved in the MAO-A pathway. Notably, our in vivo study reflected that TCPs were capable of restoring the bone loss in LPS-induced calvaria osteolysis and estrogen deficiency-induced osteoporosis models. Thus, our current work provided a potential option for the treatment of bone loss diseases and highlighted the important role of MAO-A in osteoclastogenesis as well.-Liu, Z., Yang, K., Yan, X., Wang, T., Jiang, T., Zhou, Q., Qi, J., Qian, N., Zhou, H., Chen, B., Huang, P., Guo, L., Zhang, X., Xu, X., Jiang, M., Deng, L. The effects of tranylcypromine on osteoclastogenesis in vitro and in vivo.

Development of Small-Molecules Targeting Receptor Activator of Nuclear Factor-κB Ligand (RANKL)-Receptor Activator of Nuclear Factor-κB (RANK) Protein-Protein Interaction by Structure-Based Virtual Screening and Hit Optimization.

Targeting RANKL/RANK offers the possibility of developing novel therapeutic approaches to treat bone metabolic diseases. Multiple efforts have been made to inhibit RANKL. For example, marketed monoclonal antibody drug Denosumab could inhibit the maturation of osteoclasts by binding to RANKL. This study is an original approach aimed at discovering small-molecule inhibitors impeding RANKL/RANK protein interaction. We identified compound 34 as a potent and selective RANKL/RANK inhibitor by performing structure-based virtual screening and hit optimization. Disruption of the RANKL/RANK interaction by 34 effectively inhibits RANKL-induced osteoclastogenesis and bone resorption. The expression of osteoclast marker genes was also suppressed by treatment of 34. Furthermore, 34 markedly blocked the NFATc1/c-fos pathway. Thus, our current work demonstrates that the chemical tractability of the difficult PPI (RANKL/RANK) target by a small-molecule compound 34 offers a potential lead compound to facilitate the development of new medications for bone-related diseases.

Corrigendum: Repeated Low Intensity Blast Exposure Is Associated With Damaged Endothelial Glycocalyx and Downstream Behavioral Deficits.

[This corrects the article DOI: 10.3389/fnbeh.2017.00104.].

SF-deferoxamine, a bone-seeking angiogenic drug, prevents bone loss in estrogen-deficient mice.

Deferoxamine (DFO) possesses a good chelating capability and is therefore used for the clinical treatment of ion deposition diseases. Increasing evidence shows that DFO can inhibit the activity of proline hydroxylase (PHD) by chelating iron, resulting in hypoxia-induced factor (HIF) signaling activation and angiogenesis promotion. However, clinical evidence indicates that a high concentration of DFO could be biotoxic due to its enrichment in related organs. Thus, we established a new compound by conjugating DFO with the bone-seeking agent iminodiacetic acid (IDA); the new agent is called SF-DFO, and we verified its promotion of HIF activation and tube formation in vivo. After confirming the bone-seeking property of SF-DFO in the femur and vertebra of both male and female mice and comparing it to that of DFO, we analyzed the protective effect of DFO and SF-DFO in an ovariectomized (OVX) mouse model. The serum CTX-I level revealed no influence of DFO and SF-DFO on osteoclast activity, but the blood vessels and osteoblasts in the metaphysis were more abundant after SF-DFO treatment, which resulted in a greater protective effect against trabecular bone loss compared to the DFO group. Additionally, the cortical parameters and bone strength performance were identical between the DFO and SF-DFO groups. However, the diffuse inflammatory response in the liver and spleen that occurred after DFO injection was not observed in the SF-DFO group. Thus, with reduced biotoxicity and an equivalent bone-seeking capability, SF-DFO may be a better choice for the prevention of vascular degradation-induced osteoporosis.

Small molecule nAS-E targeting cAMP response element binding protein (CREB) and CREB-binding protein interaction inhibits breast cancer bone metastasis.

Bone is the most common metastatic site for breast cancer. The excessive osteoclast activity in the metastatic bone lesions often produces osteolysis. The cyclic-AMP (cAMP)-response element binding protein (CREB) serves a variety of biological functions including the transformation and immortalization of breast cancer cells. In addition, evidence has shown that CREB plays a key role in osteoclastgenesis and bone resorption. Small organic molecules with good pharmacokinetic properties and specificity, targeting CREB-CBP (CREB-binding protein) interaction to inhibit CREB-mediated gene transcription have attracted more considerations as cancer therapeutics. We recently identified naphthol AS-E (nAS-E) as a cell-permeable inhibitor of CREB-mediated gene transcription through inhibiting CREB-CBP interaction. In this study, we tested the effect of nAS-E on breast cancer cell proliferation, survival, migration as well as osteoclast formation and bone resorption in vitro for the first time. Our results demonstrated that nAS-E inhibited breast cancer cell proliferation, migration, survival and suppressed osteoclast differentiation as well as bone resorption through inhibiting CREB-CBP interaction. In addition, the in vivo effect of nAS-E in protecting against breast cancer-induced osteolysis was evaluated. Our results indicated that nAS-E could reverse bone loss induced by MDA-MB-231 tumour. These results suggest that small molecules targeting CREB-CBP interaction to inhibit CREB-mediated gene transcription might be a potential approach for the treatment of breast cancer bone metastasis.

A Novel Rhein Derivative Modulates Bone Formation and Resorption and Ameliorates Estrogen-Dependent Bone Loss.

Osteoporosis, an osteolytic disease that affects millions of people worldwide, features a bone remodeling imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Identifying dual target-directed agents that inhibit excessive bone resorption and increase bone formation is considered an efficient strategy for developing new osteoporosis treatments. Rhein, a natural anthraquinone, can be isolated from various Asian herbal medicines. Rhein and its derivatives have been reported to have various beneficial pharmacological effects, especially their bone-targeting ability and anti-osteoclastogenesis activity. Moreover, hydrogen sulfide (H2 S) was reported to prevent ovariectomy- (OVX-) induced bone loss by enhancing bone formation, and sulfur replacement therapy has been considered a novel and plausible therapeutic option. Based on this information, we synthesized a rhein-derived thioamide (RT) and investigated its effects on bone resorption and bone formation in vitro and in vivo. It has been found that the RT-inhibited receptor activator of the nuclear factor-κB (NF-κB) ligand- (RANKL-) induced osteoclastogenesis and bone resorption in a dose-dependent manner. The expression of osteoclast marker genes was also suppressed by RT treatment. Furthermore, exploration of signal transduction pathways indicated that RT markedly blocked RANKL-induced osteoclastogenesis by attenuating MAPK pathways. However, RT treatment in an osteoblastic cell line, MC3TE-E1, indicated that RT led to an increase in the deposition of minerals and the expression of osteoblast marker genes, as demonstrated by Alizarin Red staining and alkaline phosphatase activity. Importantly, an OVX mouse model showed that RT could attenuate the bone loss in estrogen deficiency-induced osteoporosis in vivo with a smart H2 S-releasing property and that there was a considerable improvement in the biomechanical properties of bone. Accordingly, our current work highlights the dual regulation of bone remodeling by the rhein-derived molecule RT. This may be a highly promising approach for a new type of anti-osteoporosis agent. © 2018 American Society for Bone and Mineral Research.

Surgical Site Infection in Spine Surgery: Who Is at Risk?

STUDY DESIGN: Retrospective literature review of spine surgical site infection (SSI). OBJECTIVE: To perform a review of SSI risk factors and more specifically, categorize them into patient and surgical factors. METHODS: A review of published literature on SSI risk factors in adult spine surgery was performed. We included studies that reported risk factors for SSI in adult spinal surgery. Excluded are pediatric patient populations, systematic reviews, and meta-analyses. Overall, we identified 72 cohort studies, 1 controlled-cohort study, 1 matched-cohort study, 1 matched-paired cohort study, 12 case-controlled studies (CCS), 6 case series, and 1 cross-sectional study. RESULTS: Patient-associated risk factors-diabetes mellitus, obesity (body mass index >35 kg/m2), subcutaneous fat thickness, multiple medical comorbidities, current smoker, and malnutrition were associated with SSI. Surgical associated factors-preoperative radiation/postoperative blood transfusion, combined anterior/posterior approach, surgical invasiveness, or levels of instrumentation were associated with increased SSI. There is mixed evidence of age, duration of surgery, surgical team, intraoperative blood loss, dural tear, and urinary tract infection/urinary catheter in association with SSI. CONCLUSION: SSIs are associated with many risk factors that can be patient or surgically related. Our review was able to identify important modifiable and nonmodifiable risk factors that can be essential in surgical planning and discussion with patients.

A locking compression plate versus the gold-standard non-locking plate with lag screw for first metatarsophalangeal fusion: A biomechanical comparison.

INTRODUCTION: The treatment of end-stage first metatarso-phalangeal joint (MTP) arthritis has been arthrodesis. A dorsal non-locking plate with a lag screw has been the standard traditional fixation method. This study compares the biomechanical strength of a locking compression plate (LCP) with and without internal compression versus this known gold standard. METHODS: In group 1, six matched pairs of cadaver great toes were used to compare the standard non-locking dorsal plate and 3.5mm lag screw to an anatomic locking compression plate in which a lag screw was utilized rather than the internal compression features of the plate. In group 2, another six matched pairs of cadaver great toes were used to compare the gold standard to the locking compression plate, utilizing the plate's internal compression feature instead of a lag screw. A material testing system (MTS) machine applied loads to the MTP joints and measured displacement and stiffness of the constructs. The stiffness of the constructs (Young's modulus) was calculated from the force-displacement curves, and the displacement was measured. RESULTS: The locking compression plate group that used the compression features of the plate, without the lag screw, had less joint displacement and higher stiffness than control (p<0.05). The same plating construct in which a lag screw was used rather than internal compression of the plate was found to be stiffer than the control (p<0.05), but displacement was not statistically significant. DISCUSSION: The results suggest that a locking compression plate alone provides the stiffest construct for a first MTP joint fusion.

The prevention of latanoprost on osteoclastgenesis in vitro and lipopolysaccharide-induced murine calvaria osteolysis in vivo.

Identification of agents that inhibit osteoclast formation and function is important for the treatment of osteolytic diseases which feature excessive osteoclast formation and bone resorption. Latanoprost (LTP), an analog of prostaglandin F2α, is a medication which works to lower pressure inside the eyes. Prostaglandin F2α was reported to regulate bone metabolism, however, the effect of LTP in osteoclastogenesis is still unknown. Here, we found that LTP suppressed RANKL-induced osteoclastogenesis in a dose-dependent manner as illustrated by TRAP activity and TRAP staining. In addition, the osteoclast function was also reduced by LTP treatment, as indicated in less osteoclastic resorption pit areas. Furthermore, LTP inhibited the mRNA expressions of osteoclast marker genes such as TRAP and cathepsin K. In order to illustrate its molecular mechanism, we examined the changing of mRNA and protein levels of NFATc1 and c-fos by LTP treatment, as well as the phosphorylation of ERK, AKT, JNK, and p38. The results suggested that LTP inhibited RANKL-induced osteoclastgenesis and function by inhibiting ERK, AKT, JNK, and p38 cascade, following by the c-fos/NFATc1 pathway. In agreement with in vitro results, using an in vivo lipopolysaccharide-induced murine calvaria osteolysis mouse model, we found that administration of LTP was able to reverse the lipopolysaccharide-induced bone loss. Together, these data demonstrated that LTP attenuated the bone loss in lipopolysaccharide-induced murine calvaria osteolysis mice through inhibiting osteoclast formation and function. Our study thus provided the evidences that LTP was a potential treatment option against osteolytic bone diseases.

Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the pathogenesis of osteoarthritis.

15-Lipoxygenase-1 (15-LO-1) is involved in many pathological processes. The purpose of this study was to determine the potential role of 15-LO-1 in osteoarthritis (OA). The levels of 15-LO-1 expression were measured by western blotting and quantitative real-time PCR in articular cartilage from the OA rat models and OA patients. To further investigate the effects of 15-LO-1 on chondrocyte functions, such as extracellular matrix (ECM) secretion, the release of matrix-degrading enzymes, the production of reactive oxygen species (ROS), cell proliferation and apoptosis, we decreased or increased 15-LO-1 expression in chondrocytes by means of transfecting with siRNA targeting 15-LO-1 and plasmid encoding 15-LO-1, respectively. The results showed that 15-LO-1 expression was obviously increased in articular cartilage from OA rats and OA patients. It was also found that many factor-related OA, such as mechanical loading, ROS, SNP and inflammatory factor, significantly promoted 15-LO-1 expression and activity in chondrocytes. Silencing 15-LO-1 was able to markedly alleviate mechanical loading-induced cartilage ECM secretion, cartilage-degrading enzyme secretion and ROS production. Overexpression of 15-LO-1 could inhibit chondrocyte proliferation and induce chondrocyte apoptosis. In addition, reduction of 15-LO-1 in vivo significantly alleviated OA. Taken together, these results indicate that 15-LO-1 has an important role in the disease progression of OA. Thus 15-LO-1 may be a good target for developing drugs in the treatment of OA.

Repeated Low Intensity Blast Exposure Is Associated with Damaged Endothelial Glycocalyx and Downstream Behavioral Deficits.

Current clinical research into mild traumatic brain injury (mTBI) has focused on white matter changes as identified by advanced MRI based imaging techniques. However, perivascular tau accumulation in the brains of individuals diagnosed with mTBI suggests that the vasculature plays a key role in the pathology. This study used a rat model to examine whether the endothelial glycocalyx, a layer of the vasculature responsible for sensing luminal shear forces, is damaged by exposure to repeated low intensity blast, and whether this layer is associated with observed behavioral deficits. The blast exposure used consisted of 12, 40 kPa blast exposures conducted with a minimum of 24 h between blasts. We found that repeated blast exposure reduced glycocalyx length and density in various brain regions indicating damage. This blast exposure paradigm was associated with a mild performance decrement in the Morris water maze (MWM) which assesses learning and memory. Administration of hyaluronidase, an enzyme that binds to and degrades hyaluronan (a major structural component of the glycocalyx) prior to blast exposure reduced the observed behavioral deficits and induced a thickening of the glycocalyx layer. Taken together these findings demonstrate that the endothelial glycocalyx degradation following repeated blast is associated with behavioral decrements which can be prevented by treatment with hyaluronidase.

Synthesis and biological evaluation of rhein amides as inhibitors of osteoclast differentiation and bone resorption.

Approaches of targeting excessive activation and differentiation of osteoclasts were considered as an effective treatment option for osteoporosis or osteopenia. In the present work, a series of rhein derivatives were synthesized and employed for their cytotoxicity screening against bone marrow-derived macrophages cells (BMMs) and their inhibition effects on osteoclasts activation and differentiation in vitro using an MTT assay and a TRAP activity assay respectively. Two rhein derivatives d6 and d11 inhibited BMMs activation and differentiation with 98% and 85% inhibitory activity respectively, without showing any cytotoxicity on BMMs. Subsequently, the most potent compound d6 was further validated for its inhibitory effects on the formation of TRAP-positive multinucleated cells and bone resorption as evaluated by TRAP staining and bone resorption assay. The regulation by d6 of osteoclast marker genes assay revealed that treatment of BMMs with M-CSF and RANKL resulted in the stimulation of mRNA expressions of NFATc1, c-fos, TRAP, MMP-9 and cathepsin K which were highly related with osteoclast activation and differentiation, while d6 decreased mRNA expressions of these genes. It was indicated that d6 might regulate osteoclasts activity through RANKL/RANK/NFATc1 pathway. Thus our current work is expected to provide a highly promising approach for the development of a new type of anti-osteoporosis agent.

Total Elbow Arthroplasty in the United States: Evaluation of Cost, Patient Demographics, and Complication Rates.

Total elbow arthroplasty (TEA) is utilized in the treatment of rheumatoid and post-traumatic elbow arthritis. TEA is a relatively low volume surgery in comparison to other types of arthroplasty and therefore little is known about current surgical utilization, patient demographics and complication rates in the United States. The purpose of our study is to evaluate the current practice trends and associated in-patient complications of TEA at academic centers in the United States. We queried the University Health Systems Consortium administrative database from 2007 to 2011 for patients who underwent an elective TEA. A descriptive analysis of demographics was performed which included patient age, sex, race, and insurance status. We also evaluated the following patient clinical benchmarks: hospital length of stay (LOS), hospital direct cost, in-hospital mortality, complications, and 30-day readmission rates. Our cohort consisted of 3146 adult patients (36.5% male and 63.5% female) with an average age of 58 years who underwent a total elbow arthroplasty (159 academic medical centers) in the United States. The racial demographics included 2334 (74%) Caucasian, 285 (9%) black, 236 (7.5%) Hispanic, 16 (0.5%) Asian, and 283 (9%) other patients. The mean LOS was 4.2±5 days and the mean total direct cost for the hospital was 16,300±4000 US Dollars per case. The overall inpatient complication rate was 3.1% and included mortality <1%, DVT (0.8%), re-operation (0.5%), and infection (0.4%). The 30-day readmission rate was 4.4%. TEA is a relatively uncommon surgery in comparison to other forms of arthroplasty but is associated with low in-patient and 30-day perioperative complication rate. Additionally, the 30-day readmission rate and overall hospital costs are comparable to the traditional total hip and knee arthroplasty surgeries.