Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Validity and reliability of the sleep health index among patients with spinal degenerative diseases.

OBJECTIVE: To test the validity and reliability of the Sleep Health Index (SHI) in a Chinese clinical sample, and thereby provide more evidence for the assessment of sleep health in future research and clinical practice. METHODS: This study used a cross-sectional design. A convenient sample of 265 participants with spinal degenerative diseases was recruited from outpatient clinics. The SHI, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Patient Health Questionnaire-9 (PHQ-9), Visual Analogue Scale (VAS), and EuroQoL 5-Dimension 5-Level (EQ-5D-5L) were administered via REDCap. Structural, concurrent, convergent, known-group validity, internal consistency, and test-retest reliability were evaluated. RESULTS: Confirmatory factor analysis confirmed a 3-factor structure (sleep duration, sleep quality, and disordered sleep). The overall SHI score had a high correlation with PSQI and ISI (r = -0.62 and -0.70, respectively) as well as a moderate correlation with PHQ-9 (r = -0.50, p<0.001). The overall SHI was significantly associated with VAS, ESS, and EQ-5D-5L (r = -0.15 to -0.23, p<0.05). Participants with pain had a lower score on the sleep quality sub-index than those without (p<0.001). Those with chronic diseases had a significantly lower score on the sleep duration sub-index than those without (p<0.05). Those with depression, poor sleep quality, and insomnia had lower scores on the overall scale and the three sub-indices than those without (p<0.05). The overall SHI showed acceptable internal consistency (Cronbach's α = 0.74) and test-retest reliability (intraclass correlation coefficient = 0.73). CONCLUSIONS: The Chinese version of SHI showed good validity and acceptable reliability and could be used to assess sleep health among clinical populations.

TMEM135 maintains the equilibrium of osteogenesis and adipogenesis by regulating mitochondrial dynamics.

BACKGROUND: Disturbance in the differentiation process of bone marrow mesenchymal stem cells (BMSCs) leads to osteoporosis. Mitochondrial dynamics plays a pivotal role in the metabolism and differentiation of BMSCs. However, the mechanisms underlying mitochondrial dynamics and their impact on the differentiation equilibrium of BMSCs remain unclear. METHODS: We investigated the mitochondrial morphology and markers related to mitochondrial dynamics during BMSCs osteogenic and adipogenic differentiation. Bioinformatics was used to screen potential genes regulating BMSCs differentiation through mitochondrial dynamics. Subsequently, we evaluated the impact of Transmembrane protein 135 (TMEM135) deficiency on bone homeostasis by comparing Tmem135 knockout mice with their littermates. The mechanism of TMEM135 in mitochondrial dynamics and BMSCs differentiation was also investigated in vivo and in vitro. RESULTS: Distinct changes in mitochondrial morphology were observed between osteogenic and adipogenic differentiation of BMSCs, manifesting as fission in the late stage of osteogenesis and fusion in adipogenesis. Additionally, we revealed that TMEM135, a modulator of mitochondrial dynamics, played a functional role in regulating the equilibrium between adipogenesis and osteogenesis. The TMEM135 deficiency impaired mitochondrial fission and disrupted crucial mitochondrial energy metabolism during osteogenesis. Tmem135 knockout mice showed osteoporotic phenotype, characterized by reduced osteogenesis and increased adipogenesis. Mechanistically, TMEM135 maintained intracellular calcium ion homeostasis and facilitated the dephosphorylation of dynamic-related protein 1 at Serine 637 in BMSCs. CONCLUSIONS: Our findings underscore the significant role of TMEM135 as a modulator in orchestrating the differentiation trajectory of BMSCs and promoting a shift in mitochondrial dynamics toward fission. This ultimately contributes to the osteogenesis process. This work has provided promising biological targets for the treatment of osteoporosis.

3D-printed gradient scaffolds for osteochondral defects: Current status and perspectives.

Articular osteochondral defects are quite common in clinical practice, and tissue engineering techniques can offer a promising therapeutic option to address this issue.The articular osteochondral unit comprises hyaline cartilage, calcified cartilage zone (CCZ), and subchondral bone.As the interface layer of articular cartilage and bone, the CCZ plays an essentialpart in stress transmission and microenvironmental regulation.Osteochondral scaffolds with the interface structure for defect repair are the future direction of tissue engineering. Three-dimensional (3D) printing has the advantages of speed, precision, and personalized customization, which can satisfy the requirements of irregular geometry, differentiated composition, and multilayered structure of articular osteochondral scaffolds with boundary layer structure. This paper summarizes the anatomy, physiology, pathology, and restoration mechanisms of the articular osteochondral unit, and reviews the necessity for a boundary layer structure in osteochondral tissue engineering scaffolds and the strategy for constructing the scaffolds using 3D printing. In the future, we should not only strengthen the basic research on osteochondral structural units, but also actively explore the application of 3D printing technology in osteochondral tissue engineering. This will enable better functional and structural bionics of the scaffold, which ultimately improve the repair of osteochondral defects caused by various diseases.

Dysfunction of Caveolae-Mediated Endocytic TßRI Degradation Results in Hypersensitivity of TGF-ß/Smad Signaling in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen-related genes, and excessive transforming growth factor-beta (TGF-ß) signaling is a common mechanism. TGF-ß/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF-ß receptors (TßRI and TßRII). During internalization, clathrin-mediated endocytosis enhances TGF-ß/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae-mediated endocytosis turns off TGF-ß/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2oim , osteogenesis imperfecta murine [oim]/oim mouse), we found that osteoblastic cells of oim/oim mice were more sensitive to the inhibitory effects of TGF-ß on osteoblast differentiation and maturation and had much higher cell membrane protein levels of TGF-ß receptors than those of wild-type (wt)/wt mice. Further results showed that clathrin-mediated endocytosis of TßRI was enhanced, whereas caveolae-mediated TßRI endocytic degradation was reduced in oim/oim mice, combined with reduced caveolin-1 (Cav-1) phosphorylation. In addition, type I collagen downregulated TßRI via focal adhesion kinase (FAK) and Src activation-dependent Cav-1 phosphorylation. To further examine this mechanism, 4-week-old oim/oim and wt/wt mice were treated with either TßRI kinase inhibitor (SD-208) or vehicle for 8 weeks. SD-208 treatment significantly reduced the fracture incidence in oim/oim mice. Micro-computed tomography and biomechanical testing showed that femoral bone mass and strength were significantly improved with SD-208 treatment in both genotypes. Additionally, SD-208 significantly promoted osteoblast differentiation and bone formation and inhibited bone resorption. In conclusion, dysfunction of caveolae-mediated endocytic TßRI degradation is a possible mechanism for the enhanced TGF-ß/Smad signaling in OI. Targeting this mechanism using a TßRI kinase inhibitor effectively reduced fractures and improved bone mass and strength in OI model and, thus, may offer a new strategy for the treatment of OI. © 2022 American Society for Bone and Mineral Research (ASBMR).

Cervical nerve root variant: report of two cases under the cervical endoscopy and review of clinical literature.

BACKGROUND: We know of five cases of cervical nerve root variants that have been reported, all of which were found during posterior cervical surgery. We reported two cases of cervical nerve root variants. One had two anomalous branches of the C7 root, is the other had a C5, C6 nerve root communication branch. CASE DESCRIPTION: A 62-year-old female presented with neck and right upper extremity pain, accompanied by hypaesthesia in her right forearm for 4 months. Preoperative X-ray film, magnetic resonance imaging (MRI) and computed tomography (CT) scan demonstrated C6-7 uncovertebral joint hyperplasia and foraminal stenosis. She underwent posterior cervical endoscopic foraminoplasty. The right C7 nerve root was observed to have two anomalous branches originated from a proximal trunk. After the surgery, the symptoms resolved. A 54-year-old female presented with radiating pain and numbness in her right arm and hand for 4 months. Preoperative MRI showed a C5/6 intervertebral disc herniation. She had hypaesthesia in radial side of her right arm and 1st-3rd fingers. Posterior cervical endoscopic foraminalplasty was performed for the patient. After decompression of the bony wall of the posterior nerve root canal, a 2-mm thick communicating nerve was observed emerging from the dura with the C6 nerve root and exiting to the caudal level. After the surgery, the symptoms resolved immediately. CONCLUSIONS: Cervical nerve root variant may be more apparent on edoscopic approaches to the cervical foraminae than at open surgery.

Suspected allergy to titanium after anterior cervical discectomy and fusion using a Zero-P device: a case report.

PURPOSE: Cases of allergy to large surgical implants have been reported. However, few studies have reported allergy to small titanium-containing implants (e.g. Zero-P device). METHODS: We reported the case of a 51-year old male patient who underwent the anterior cervical discectomy and fusion (ACDF) procedure using a Zero-P device and exhibited allergic symptoms 1 month after the surgery. RESULTS: The allergic symptoms included intermittent tingling and itches in the throat induced by speaking. Systemic rashes over the skin surface and congestion of the eyeball, and dysphagia were also present. Anti-allergic treatment did not resolve the symptoms. Patch tests revealed negative reactions to the rested reagents including titanium. Radiographic results showed solid bone fusion and no signs of chronic inflammation or hypotoxic infection in the surrounding tissues. Upon the patient's request, we removed the titanium screws and plate of the Zero-P device. No allergic reactions were observed after the surgery and at a 6-month follow-up. CONCLUSIONS: Even with a small implant such as the Zero-P device, allergy to titanium may still occur. This case demonstrated the need to screen for the presence of allergy to metals including titanium before the surgery.

Irisin reduces bone fracture by facilitating osteogenesis and antagonizing TGF-ß/Smad signaling in a growing mouse model of osteogenesis imperfecta.

Objective: Osteogenesis imperfecta (OI) is a congenital disorder characterized by muscle defect and skeletal fragility, and no cure is yet available. Crosstalk between bone and muscle has become a new coming focus of therapeutic strategy in OI. Irisin, a secreted myokine, was found to be involved in regulating bone metabolism, and may be beneficial for the treatment of OI. However, its effects in OI have yet to be determined. This study sought to determine whether Irisin therapy is capable of reducing fracture risk in OI and to investigate the potential mechanisms of action. Methods: Fibronectin type III domain containing 5 (FNDC5)/Irisin expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. In vivo, X-ray was used for fracture counting and micro-CT, dynamic histomorphometry analysis, immunohistochemistry, histomorphometry, and biomechanical test were used to evaluate the effects of Irisin on fracture frequency and bone quality in OI mouse model, oim/oim mouse. In vitro, osteogenesis-related gene expressions were determined by quantitative real-time PCR (qRT-PCR), western blot, and osteoblastogenesis assay were assessed by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining. Mechanistically, cell immunofluorescence staining, co-immunoprecipitation (co-IP) (Co-IP), molecular docking, western blot, luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay were used for elucidating the mechanisms of how Irisin antagonized transforming growth factor-ß (TGF-ß)/Smad signaling in oim/oim osteoblasts and further attenuated the inhibitory effect of TGF-ß1 on osteogenic differentiation. Results: Musculoskeletal system-related FNDC5/Irisin was decreased in the serum, muscle, and bone in oim/oim mice. Irisin administration reduced bone fracture and attenuated bone abnormalities by improving bone mass and strength and facilitating the expression of osteogenic differentiation markers. In vivo study and in vitro experiments showed that Irisin antagonized TGF-ß/Smad signaling by interfering with TGF-ß1-TGF-ß receptor II (TßRII) binding. In oim/oim osteoblasts, Irisin alleviated TGF-ß1-induced suppression of osteogenic differentiation through both integrin-dependent and integrin-independent mechanisms. Independent of integrin receptors, Irisin affected osteogenesis by activating ERK/p38 signaling and counteracting TGF-ß/Smad2/3 signaling. In particular, Irisin alleviated TGF-ß1-induced inhibition of Runx2 function at the osteocalcin promoter through decreasing Smad2/3 signaling and inducing HADC4/5 degeneration. Conclusions: Collectively, Irisin could effectively reduce bone fracture in oim/oim mice through promoting osteogenesis and counteracting TGF-ß/Smad signaling. Translational potential statement: Findings from this study provided evidence for using Irisin as a potential therapeutic reagent to prevent the progression of OI.

Clinical Outcomes of Percutaneous Endoscopic Lumbar Discectomy Assisted With Sequential SNRB in Treating Lumbosacral Contiguous Double-Level Disc Herniation.

BACKGROUND: For patients with lumbosacral contiguous double-level disc herniation, there has been no consensus on which level(s) should be treated. Selective nerve root block (SNRB) can identify the pain-generating nerve root; however, its diagnostic accuracy remains controversial due to potential spread of the injectate. Sequential SNRB from S1 to L5 may improve the diagnostic specificity. OBJECTIVES: To examine the clinical and radiographic outcomes of percutaneous endoscopic lumbar discectomy (PELD) assisted with sequential SNRB from S1 to L5 in patients who had lumbosacral contiguous double-level disc herniation. STUDY DESIGN: A retrospective design was used. SETTING: This study was conducted in a university-affiliated tertiary hospital in Shanghai, China. METHODS: Fifty-eight consecutive patients with lumbosacral contiguous double-level disc herniation were included (January 2018 to January 2021). Sequential SNRB from S1 to L5 was performed to identify the symptomatic level(s), followed by PELD based on the results of sequential SNRB. Clinical outcomes were assessed by the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and modified Macnab criteria. Pre- and post-operation radiologic and clinical parameters were evaluated. Demographics were retrieved from medical records. RESULTS: Patients were followed-up with an average duration of 18.6 months. Among the 58 patients, 21 received surgical treatment at L4/L5 level, 25 at L5/S1 level, and 12 at both levels based on the results of sequential SNRB from S1 to L5. Compared with preoperative values, mean VAS scores for leg and back pain, as well as the ODI score, improved significantly after the surgery. There were no significant differences in the clinical outcomes between patients receiving surgical treatment at L4/L5, L5/S1, or both levels. According to the Macnab criteria, 49 patients (84.5%) had excellent or good results. LIMITATIONS: This study used a retrospective design with relatively small sample size and medium follow-up duration. CONCLUSIONS: Sequential SNRB from S1 to L5 was an effective approach to guide PELD treatment for patients with lumbosacral contiguous double-level disc herniation. Health care providers may consider using this approach to facilitate future clinical practice.

Alendronate-functionalized double network hydrogel scaffolds for effective osteogenesis.

Development of artificial bone substitutes mimicking the extracellular matrix is a promising strategy for bone repair and regeneration. In views of the actual requirement of biomechanics, biodegradability, and bioactivity, herein, a double-network (DN) hydrogel was constructed by interspersing a methacrylated gelatin (GelMA) network into alendronate (ALN)-modified oxidized alginate (OSA) network via Schiff base reaction and photo-crosslinking process to promote in situ bone regeneration. This GelMA@OSA-ALN DN hydrogel possessed favorable network and pores, good biocompatibility, and enhanced biomechanics. Notably, the introduction of Schiff base furnished the ND hydrogel scaffold with pH-responsive biodegradation and sustained ALN drug release delivery, which could provide effective bioactivity, upregulate osteogenesis-related genes, and promote the cell viability, growth, proliferation, and osteogenesis differentiation for bone regeneration. Therefore, we provide a new insight to develop functional DN hydrogel scaffold toward governing the on-demand drug release and achieving the stem cell therapy, which will be developed into the minimally invasive gelling system to prolong local delivery of bisphosphonates for the bone-related diseases.

Alendronate modified mPEG-PLGA nano-micelle drug delivery system loaded with astragaloside has anti-osteoporotic effect in rats.

Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (-23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10-200 µg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.

Formulation of pH-responsive PEGylated nanoparticles with high drug loading capacity and programmable drug release for enhanced antibacterial activity.

In the current global crisis of antibiotic resistance, delivery systems are emerging to combat resistant bacteria in a more efficient manner. Despite the significant advances of antibiotic nanocarriers, many challenges like poor biocompatibility, premature drug release, suboptimal targeting to infection sites and short blood circulation time are still challenging. To achieve targeted drug delivery and enhance antibacterial activity, here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin (PEG-Schiff-Van) prodrug and free Van in one drug delivery system. The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition. Notably, on account of the combination of physical encapsulation and chemical conjugation of vancomycin, these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior, which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period. In addition, more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity. Using this strategy, this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites, thereby presenting prominent antibacterial therapy both in vitro and in vivo. This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles, which would be a promising class of antimicrobial materials for potential clinical translation.

Fabrication of Naturally Derived Double-Network Hydrogels With a Sustained Aspirin Release System for Facilitating Bone Regeneration.

Continuous efforts on pursuit of effective drug delivery systems for engineering hydrogel scaffolds is considered a promising strategy for the bone-related diseases. Here, we developed a kind of acetylsalicylic acid (aspirin, ASA)-based double-network (DN) hydrogel containing the positively charged natural chitosan (CS) and methacrylated gelatin (GelMA) polymers. Combination of physical chain-entanglement, electrostatic interactions, and a chemically cross-linked methacrylated gelatin (GelMA) network led to the formation of a DN hydrogel, which had a suitable porous structure and favorable mechanical properties. After in situ encapsulation of aspirin agents, the resulting hydrogels were investigated as culturing matrices for adipose tissue-derived stromal cells (ADSCs) to evaluate their excellent biocompatibility and biological capacities on modulation of cell proliferation and differentiation. We further found that the long-term sustained ASA in the DN hydrogels could contribute to the anti-inflammation and osteoinductive properties, demonstrating a new strategy for bone tissue regeneration.

Myricetin Loaded Nano-micelles Delivery System Reduces Bone Loss Induced by Ovariectomy in Rats Through Inhibition of Osteoclast Formation.

In recent years, much attention has been paid to the therapeutic effects of phytochemicals on osteoporosis. Other studies have shown that myricetin (MY) could promote osteogenic activity and inhibit osteoclastic effect, albeit little is known about effect of MY micellar system on osteoporosis. Therefore, we sought to discuss the therapeutic effect and mechanism of MY-loaded bone-targeting micelles on osteoporosis induced by ovariectomy (OVA) in rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles were prepared via ethanol injection method, while in vitro release study, bone targeting, pharmacokinetic studies, and the effect on proliferation of osteoblasts were investigated. Further, the therapeutic effect on osteoporosis was studied through ovariectomized rats. Compared with free MY, oral bioavailability of AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles in rats was increased by 3.54 times. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles exhibited bone targeting potential, and could significantly increase the activity of alkaline phosphatase and promote the proliferation of osteoblasts. Importantly, AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles mainly regulated bone metabolism by inhibiting bone resorption, thereby improving the symptoms of osteoporosis in OVA rats. The AL-P(LLA-CL)-PEG-P(LLA-CL)-MY micelles substantially enhanced the oral bioavailability of MY and demonstrated good bone targeting capability, thereby suggesting its prospect as carrier for osteoporotic improvement in OVA rats.

Feasibility of sleep extension and its effect on cardiometabolic parameters in free-living settings: a systematic review and meta-analysis of experimental studies.

AIMS: Inadequate sleep is a global health issue and has been associated with an increased risk for cardiovascular diseases. As a part of sleep hygiene, intentional lengthening of night-time sleep duration (i.e. sleep extension) might be a behavioural intervention to improve cardiometabolic health. To examine the feasibility of sleep extension and its effects on cardiometabolic parameters in free-living settings. METHODS AND RESULTS: This review was registered in PROSPERO (CRD42019146174). Five databases were searched. Only experimental studies conducted in adults without a diagnosis of sleep disorder were included. The pooled mean difference was calculated by the inverse variance method. Narrative summaries were also used. Thirteen studies from 11 trials were included. The intervention ranged from 3 days to 6 weeks. Sleep extension increased total sleep time by 51 min [95% confidence interval (CI) 39-63]. Overall, sleep extension did not result in significant changes in blood pressure. However, sub-group analysis revealed that when 24 h mean blood pressure was obtained among those with pre-hypertension or Stage 1 hypertension, sleep extension reduced systolic (weighted mean difference = -7.8 mm/Hg; 95% CI -10.6 to -4.9), and diastolic blood pressure (weighted mean difference = -4.2 mm/Hg; 95% CI -6.7 to -1.8). The pooled effects on fasting glucose and insulin resistance were not significant. The effect of sleep extension on other parameters (e.g. heart rate) was not consistent. CONCLUSION: Sleep extension is feasible and could increase sleep in free-living settings. Sleep extension shows promise for reducing 24 h mean blood pressure among those with pre-hypertension or hypertension. More large-scale studies are needed to examine its long-term effects.

Morphology of Herniated Disc as a Predictor for Outcomes of Posterior Percutaneous Full-endoscopic Cervical Discectomy in Treating Cervical Spondylotic Radiculopathy.

OBJECTIVE: To quantitively characterize the morphology of cervical disc herniation (CDH) causing cervical spondylotic radiculopathy (CSR) and investigate whether the morphological features of CDH are associated with clinical outcomes in CSR patients treated by posterior percutaneous full-endoscopic cervical discectomy (PPECD). METHODS: This is a single-center retrospective study. Eighty-seven PPECD-treated patients meeting the inclusion criteria were included between May 2017 and May 2019. Based on preoperative T2-weighted magnetic resonance imaging (MRI), we designed and measured six morphological parameters of CDH for all patients to reflect its relative position to cervical spinal cord and protruding degree: DC-SC distance from the center of disc (DC) and the center of spinal cord (SC); DC-DP distance from the center of cervical disc (DC) to the peak of herniation (DP); internal diameter of the disc; axial length of CDH; central angle of CDH formed by central axes of CDH and spinal cord; the modified index of CDH. We recorded general information, neck disability index (NDI) scores, visual analog scale (VAS) scores of neck and arm of all patients preoperatively and postoperatively at 1-year follow-up. The association of preoperative general variables and morphological parameters with clinical outcomes were explored by utilizing logistic regression and receiver operating characteristic curve (ROC) analysis. RESULTS: The preoperative neck-VAS, arm-VAS, and NDI were significantly decreased after PPECD and remained at a low value at follow-up. In regards to the morphological parameters of CDH, the mean value of DC-SC distance, DC-DP distance, internal diameter of the disc, axial length of CDH, central angle of CDH, and modified index of CDH were 1.61 ± 0.30 cm, 1.66 ± 0.32cm, 1.04 ± 0.21 cm, 0.63 ± 0.19cm, 39.38° ± 11.94°, and 0.39 ± 0.24, respectively. For patients grouped by difference in the recovery rate of NDI and arm-VAS (excellent improved group, EI; and limited improved group, LI), there were no differences in the age, gender, surgical segments, and morphological parameters, except for the central angle of CDH. According to binary logistic regression analysis, only the preoperative central angle of CDH was significantly associated with postoperative NDI recovery (odds ratio: 0.873; 95% confidence interval: 0.819-0.931, P = 0.002). ROC analysis showed the optimal cut-off value of the central angle of CDH for predicting the postoperative improvement of functional outcomes is 33.788°. CONCLUSION: Preoperative morphology of CDH is related to the outcomes of CSR patients after PPECD. Patients with a large central angle of CDH (>33.788°) have more likelihood of ameliorating neurological symptoms of CSR. There is the potential to select the central angle of CDH as a predictor for outcomes of PPECD in treating CSR.

Clinical Outcomes of Posterior Percutaneous Endoscopic Cervical Foraminotomy and Discectomy Assisted with SNRB in Treating Cervical Radiculopathy with Diagnostic Uncertainty.

BACKGROUND: Selective nerve root block (SNRB) has been used to facilitate the diagnostic process when radiologic abnormalities are not correlated with clinical symptomatology in patients with cervical radiculopathy. Meanwhile, minimally invasive posterior percutaneous endoscopic cervical foraminotomy and discectomy (PPECFD) has been widely used to treat cervical radiculopathy because of its advantages. However, combination of these 2 procedures in the treatment of cervical radiculopathy with diagnostic uncertainty has not been reported. OBJECTIVES: To examine the clinical outcomes of PPECFD assisted with SNRB in patients who had cervical radiculopathy with diagnostic uncertainty. STUDY DESIGN: A retrospective design was used. SETTING: This study was conducted in a university-affiliated tertiary hospital in Shanghai, China. METHODS: Thirty consecutive patients with cervical radicular pain who had diagnostic uncertainty were included (January 2018 to January 2019). Diagnostic SNRB was performed to identify the responsible nerve root(s). PPECFD was selected as the treatment when the SNRB result was positive. Clinical outcomes were assessed by the Visual Analog Scale (VAS), Neck Disability Index (NDI), and modified Macnab criteria. Pre- and post-operative radiologic and clinical parameters were evaluated. Other information was retrieved from the electronic records. RESULTS: All patients had successful SNRB procedures. Four were excluded from the analysis because of the negative results of the SNRB. Among the remaining 26 patients who underwent the subsequent PPECFD surgery, the mean follow-up was 14 months. Compared with preoperative values, the mean VAS scores for radicular arm pain and neck pain, as well as the NDI score, improved significantly. According to the Macnab criteria, 22 patients (84.6%) had excellent or good results. No major peri- and postoperative complications were observed. LIMITATIONS: This study used a retrospective design with relatively small sample size and medium follow-up duration. CONCLUSIONS: Diagnostic SNRB may be a helpful tool to identify the origin of cervical radicular pain for patients with diagnostic uncertainty. With the guidance of SNRB, PPECFD is likely to be an effective and safe option for the treatment of cervical radiculopathy with diagnostic uncertainty.

Clinical and radiological outcomes of endoscopic foraminoplasty and decompression assisted with preoperative planning software for lumbar foraminal stenosis.

PURPOSE: To assess the clinical and radiological outcomes of using endoscopic foraminoplasty and decompression assisted with a preoperative planning software in the treatment of lumbar foraminal stenosis. METHODS: This retrospective study included 43 patients with lumbar foraminal stenosis (Jan 2018 and June 2019). These patients were divided into two groups. Patients in the conventional group (group A) underwent endoscopic lumbar foraminoplasty and decompression. Patients in the experimental group (group B) underwent the same surgery assisted with a preoperative software. The total operation time, puncture-channel establishment time, and the number of intraoperative fluoroscopic images taken were recorded. The Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were administered preoperatively and postoperatively (at 1-month, 3-month, and 12-month follow-up). The modified MacNab criteria were used to assess the global outcome at 12-month follow-up. RESULTS: Patients in group B had shorter operation time, puncture-channel establishment time, and less number of intraoperative fluoroscopic images taken, as compared with group A. The VAS and ODI scores were significantly lower than pre-operation for both groups at all follow-ups. No significant difference was observed between these two groups. Based on the modified MacNab criteria, the excellent-to-good rate was 86.4% in group A and 90.5% in group B, respectively. After the operation, no patients had residual osteophytes in group B, while two patients still had residual osteophytes and foraminal stenosis in group A. CONCLUSION: For endoscopic surgery treating lumbar foraminal stenosis, using preoperative planning software could reduce the puncture-channel establishment time, operation time, and the number of intraoperative fluoroscopic images taken without affecting the clinical outcomes.

Prehospital aortic blood flow control techniques for non-compressible traumatic hemorrhage.

Non-compressible hemorrhage in the junctional areas and torso could be life-threatening and its prehospital control remains extremely challenging. The aim of this review was to compare commonly used techniques for the control of non-compressible hemorrhage in prehospital settings, and thereby provide evidence for further improvements in emergency care of traumatic injuries. Three techniques were reviewed including external aortic compression (EAC), abdominal aortic junctional tourniquet (AAJT), and resuscitative endovascular balloon occlusion of the aorta (REBOA). In prehospital settings, all three techniques have demonstrated clinical effectiveness for the control of severe hemorrhage. EAC is a cost- and equipment-free, easy-to-teach, and immediately available technique. In contrast, AAJT and REBOA are expensive and require detailed instructions or systematic training. Compared with EAC, AAJT and REBOA have greater potentials in the management of traumatic hemorrhage. AAJT can be used not only in the junctional areas but also in pelvic and bilateral lower limb injuries. However, both AAJT and REBOA should be used for a limited time (less than 1 hour) due to possible consequences of ischemia and reperfusion. Compared with EAC and AAJT, REBOA is invasive, requiring femoral arterial access and intravascular guidance and inflation. Mortality from non-compressible hemorrhage could be reduced through the prehospital application of aortic blood flow control techniques. EAC should be considered as the first-line choice for many non-compressible injuries that cannot be managed with conventional junctional tourniquets. In comparison, AAJT or REBOA is recommended for better control of the aorta blood flow in prehospital settings. Although these three techniques each have advantages, their use in trauma is not widespread. Future studies are warranted to provide more data about their safety and efficacy.

Comparable Effects of Strontium Ranelate and Alendronate Treatment on Fracture Reduction in a Mouse Model of Osteogenesis Imperfecta.

Alendronate (Aln) has been the first-line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three-week-old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR- and Aln-treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.