Risk factors of instrumentation failure after laminectomy and posterior cervical fusions (PCF).

BACKGROUND: For patients with multilevel degenerative cervical myelopathy, laminectomy and posterior cervical fusions (PCF) with instrumentation are widely accepted techniques for symptom relief. However, hardware failure is not rare and results in neck pain or even permanent neurological lesions. There are no in-depth studies of hardware-related complications following laminectomy and PCF with instrumentation. METHODS: The present study was a retrospective, single centre, observational study. Patients who underwent laminectomy and PCF with instrumentation in a single institution between January 2019 and January 2021 were included. Patients were divided into hardware failure and no hardware failure group according to whether there was a hardware failure. Data, including sex, age, screw density, end vertebra (C7 or T1), cervical sagittal alignment parameters (C2-C7 cervical lordosis, C2-C7 sagittal vertical axis, T1 slope, Cervical lordosis correction), regional Hounsfield units (HU) of the screw trajectory and osteoporosis status, were collected and compared between the two groups. RESULTS: We analysed the clinical data of 56 patients in total. The mean overall follow-up duration was 20.6 months (range, 12-30 months). Patients were divided into the hardware failure group (n = 14) and no hardware failure group (n = 42). There were no significant differences in the general information (age, sex, follow-up period) of patients between the two groups. The differences in fusion rate, fixation levels, and screw density between the two groups were not statistically significant (p > 0.05). The failure rate of fixation ending at T1 was lower than that at C7 (9% vs. 36.3%) (p = 0.019). The regional HU values of the pedicle screw (PS) and lateral mass screw (LMS) in the failure group were lower than those in the no failure group (PS: 267 ± 45 vs. 368 ± 43, p = 0.001; LMS: 308 ± 53 vs. 412 ± 41, p = 0.001). The sagittal alignment parameters did not show significant differences between the two groups before surgery or at the final follow-up (p > 0.05). The hardware failure rate in patients without osteoporosis was lower than that in patients with osteoporosis (14.3% vs. 57.1%) (p = 0.001). CONCLUSIONS: Osteoporosis, fixation ending at C7, and low regional HU value of the screw trajectory were the independent risk factors of hardware failure after laminectomy and PCF. Future studies should illuminate if preventive measures targeting these factors can help reduce hardware failure and identified more risk factors, and perform long-term follow-up.

Myth or fact: 3D-printed off-the-shelf prosthesis is superior to titanium mesh cage in anterior cervical corpectomy and fusion?

BACKGROUND: To find out if three-dimensional printing (3DP) off-the-shelf (OTS) prosthesis is superior to titanium mesh cages in anterior cervical corpectomy and fusion (ACCF) when treating single-segment degenerative cervical spondylotic myelopathy (DCSM). METHODS: DCSM patients underwent ACCF from January 2016 to January 2019 in a single center were included. Patients were divided into the 3DP group (28) and the TMC group (23). The hospital stays, operation time, intraoperative blood loss, and the cost of hospitalization were compared. The Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI) were recorded pre-operatively, 1 day, 3, 6, 12, and 24 months post-operatively. Radiological data was measured to evaluate fusion, subsidence, and cervical lordosis. Patients were sent with SF-36 to assess their health-related quality of life (HRQoL). RESULTS: The differences in operative time, intraoperative blood loss, and hospital stay were not statistically significant between groups (p > 0.05). Postoperative dysphagia occurred in 2 cases in the 3DP group and 3 cases in the TMC group, which all relieved one week later. The difference in improvement of JOA and NDI between the two groups was not statistically significant (p > 0.05). No hardware failure was found and bony fusion was achieved in all cases except one in the 3DP group. The difference in cervical lordosis (CL), fused segmental angle (FSA), mean vertebral height (MVH), and subsidence rates between groups at each follow-up time point was not statistically significant and the results of the SF-36 were similar (p > 0.05). The total cost was higher in the 3DP group with its higher graft cost (p < 0.05). CONCLUSION: In treating single-segment DCSM with ACCF, both 3DP OTS prosthesis and TMC achieved satisfactory outcomes. However, the more costly 3DP OTS prosthesis was not able to reduce subsidence as it claimed.

Sagittal alignment of diverse mechanical complications following adult spinal deformity surgery.

PURPOSE: To compare the sagittal alignment of patients with diverse mechanical complications (MCs) following adult spinal deformity (ASD) surgery with that of patients without MCs. METHODS: A total of 371 patients who underwent ASD surgery were enrolled. The sagittal spinopelvic parameters were measured preoperatively and at the 6-month and last follow-up, and the global alignment and proportion (GAP) score was calculated. The subjects were divided into non-MC and MCs groups, and the MCs group was further divided into rod fracture (RF), screw breakage (SB), screw dislodgement (SD) and proximal junctional kyphosis (PJK) subgroups. RESULTS: Preoperatively, the RF group had greater thoracolumbar kyphosis (TLK) and relative upper lumbar lordosis (RULL); the SB group had the largest pelvic incidence (PI) and lumbar lordosis (LL); the SD group had the least global sagittal imbalance; and the PJK group had the highest thoracic kyphosis (TK), TLK and RULL. At the last follow-up, the RF and SB groups featured a large PI minus LL (PI-LL), while the PJK group featured a prominent TK; all the MCs subgroups had sagittal malalignment and a higher GAP score, and the SB group had the most severe cases. Logistic regressions showed that the relative spinopelvic alignment (RSA) score was correlated with RF, SB and SD, while the RSA and age scores were associated with PJK. CONCLUSION: Each patient with MCs had individual characteristics in the sagittal plane following ASD surgery, which may be helpful to understand the pathophysiology of poor sagittal alignment with its subsequent MCs and guide an eventual revision strategy.

Relationships between lumbar lordosis correction and the change in global tilt (GT) in adult spinal deformity.

PURPOSE: This study aimed to explore the relationships between lumbar lordosis (LL) correction and improvement of postoperative global sagittal alignment and to establish corresponding linear regressions to predict the change in global tilt (GT) based on the corrected LL following adult spinal deformity (ASD) surgery. METHODS: A total of 240 ASD patients who underwent lumbar correction were enrolled in this multicentre study. The following sagittal parameters were measured pre- and postoperatively: thoracic kyphosis (TK), LL, upper and lower LL (ULL and LLL), pelvic tilt (PT), sagittal vertical axis (SVA) and GT. The correlations among the changes in GT (△GT), SVA (△SVA), PT (△PT), TK (△TK), LL (△LL), ULL (△ULL) and LLL (△LLL) were assessed, and linear regressions were conducted to predict △GT, △SVA, △PT and △TK from △LL, △ULL and △LLL. RESULTS: △LL was statistically correlated with △GT (r = 0.798, P < 0.001), △SVA (r = 0.678, P < 0.001), △PT (r = 0.662, P < 0.001) and △TK (r = - 0.545, P < 0.001), and the outcomes of the linear regressions are: △GT = 3.18 + 0.69 × â–³LL (R2 = 0.636), △SVA = 4.78 + 2.57 × â–³LL (R2 = 0.459), △PT = 2.57 + 0.34 × â–³LL (R2 = 0.439), △TK = 7.06-0.43 × â–³LL (R2 = 0.297). In addition, △LLL had more correlations with △GT, △SVA and △PT, while △ULL had more correlations with △TK. CONCLUSION: Surgical correction of LL could contribute to the restoration of global sagittal morphology following ASD surgery. These models were established to predict the changes in sagittal parameters, in particular △GT, determined by △LL, which has not been previously done and may help to customize a more precise correction plan for ASD patients.

Predicting thoracic kyphosis morphology and the thoracolumbar inflection point determined by individual lumbar lordosis in asymptomatic adults.

PURPOSE: The aims of this study were to explore the correlations between thoracic kyphosis (TK) and lumbar lordosis (LL) parameters and to build corresponding linear regressions to predict TK morphology and the thoracolumbar inflection point (IP) determined by individual LL parameters in asymptomatic adults. METHODS: A total of 280 adult healthy volunteers were recruited, and full-spine X-rays were performed for each subject in a standing posture. The following sagittal parameters were measured: cumulative TK, LL, proximal LL (PLL), the apices of TK (TKA) and LL (LLA), the IP and the distance from the plumb line of the thoracic apex (TAPL) and the lumbar apex (LAPL) to the gravity line. The correlations between TK and LL parameters were analyzed, and the corresponding linear regressions were conducted. RESULTS: Extensive variations existed in TK alignment, including angular and morphological parameters. In addition, there were statistical correlations of all cumulative TK angles with LL (r values from - 0.173 to - 0.708) and PLL (r values from - 0.206 to - 0.803), TKA and IP with LLA (rs = 0.359 and 0.582, respectively) and TAPL with LAPL (rs = 0.335). The common predictive formulas employed in ASD surgery could include T10-L1 = - 3.6-0.2*LL (R2 = 0.201), T4-L1 = 3.4-0.5*LL (R2 = 0.457), TKA = - 10.3 + 1.1*LLA (R2 = 0.180) and IP = - 12.7 + 1.6*LLA (R2 = 0.330). CONCLUSION: There were intimate associations between TK and LL parameters in asymptomatic adults. Moreover, predictive models for thoracic alignment, particularly cumulative TK, based on LL parameters were proposed, which could better delineate anatomical relationships, guide thoracic construction during adult spinal deformity surgery and may help preventing proximal junctional failure.

Myoblast-derived exosomal Prrx2 attenuates osteoporosis via transcriptional regulation of lncRNA-MIR22HG to activate Hippo pathway.

BACKGROUND: Sarcopenia and osteoporosis are common diseases that predominantly affect older individuals. The interaction between muscle and skeleton exerts pivotal roles in bone remodeling. This study aimed to explore the function of myoblast-derived exosomal Prrx2 in osteogenic differentiation and its potential mechanisms. METHODS: Exosomes were isolated from myogenic differentiated C2C12 cells. qRT-PCR and Western blotting were used to determine target molecule expression. Osteogenic differentiation of BMSCs was evaluated by Alizarin red staining, ALP activity and levels of OCN, OPN, RUNX2, and BMP2. Dual-luciferase reporter assay, RIP, and ChIP assays were performed to verify the interaction between molecules. The nuclear translocation of YAP1 was observed by immunofluorescence staining. In vivo osteoporotic model was established by ovariectomy in mice. Bone loss was examined using HE staining. RESULTS: Prrx2 expression was elevated in myogenic differentiated C2C12 cells and their exosomes. Myoblast-derived exosomal Prrx2 enhanced osteogenic differentiation of BMSCs. Delivering exosomal Prrx2 directly bond to MIR22HG promoter and promoted its transcription and expression. MIR22HG enhanced expression and nuclear translocation of YAP via sponging miR-128, thus facilitating BMSC osteogenic differentiation. Knockdown of exosomal Prrx2 suppressed osteogenic differentiation, which could be abolished by MIR22HG overexpression. Similarly, miR-128 inhibitor or YAP overexpression reversed the inhibitory effect of MIR22HG depletion or miR-128 mimics on osteogenic differentiation. Finally, myoblast-derived exosomal Prrx2 alleviated osteoporosis in mice via up-regulating MIR22HG and activating the Hippo pathway. CONCLUSION: Myoblast-derived exosomal Prrx2 contributes to transcriptional activation of MIR22HG to activate YAP pathway via sponging miR-128, thereby facilitating osteogenic differentiation of BMSCs.

Is 3D-printed prosthesis stable and economic enough for anterior spinal column reconstruction after spinal tumor resection? A retrospective comparative study between 3D-printed off-the-shelf prosthesis and titanium mesh cage.

OBJECT: To investigate the stability and cost-effectiveness of the three-dimensional-printed (3DP) off-the-shelf (OTS) prosthesis in the reconstruction of the anterior column of the thoracic/lumbar spine after tumor resection. METHODS: Thirty-five patients (26 with primary malignant tumors and nine with metastatic malignant tumors) who underwent tumor resection and anterior column reconstruction between January 2014 and January 2019 were included in a single institute. Patients were divided into the 3DP OTS prosthesis (3DP) group (n = 14) and the titanium mesh cage (TMC) group (n = 21) by the type of implant. The operation time, intraoperative blood loss, hospital stay, history of radiotherapy, surgical level and total cost were collected and compared between the two groups. Mechanical complications and radiological parameters including mean vertebral height, subsidence, fixation failure(nonunion, migration, screw loosening, rod breakage) rate were recorded at preoperation, 1 week, 3 months, 6 months, 12 months after surgery then at 1 year interval or stop until the end of survival. The follow-up patients were also sent with short form-36 to assess their health-related quality of life (HRQoL) and questions about the current condition of their disease. RESULTS: The mean overall follow-up was 24.6 months. Of the 35 patients involved, six patients died and six were lost to follow-up. The differences between the two groups in operative time, intraoperative blood loss, and hospital stay were not statistically significant (p > 0.05). The differences in fixation failure and the subsidence rate between the two groups were not statistical significant (p > 0.05). The difference of subsidence rate between the cases with and without osteoporosis, cases with and without radiotherapy was statistically significant within each group (p < 0.05). However, the difference of subsidence rate between the surgical level above or below T10 was not statistically significant (p > 0.05). The response rate of the questionnaire among the survived patients was 100% (23/23 patients). The results of the Short Form- (SF-)36 between the two groups were similar (p > 0.05). The total cost was higher in the 3DP group (p < 0.05) with its higher graft cost (p < 0.05), but the differences in internal fixation cost and other cost were not statistically significant between groups (p > 0.05). CONCLUSION: Compared to TMC, the 3DP OTS prosthesis achieved similar clinical and radiological results in spinal anterior spinal column reconstruction of thoracic/lumbar spinal tumor resection. However, the 3DP OTS prosthesis was more expansive than TMC.

Predictive formulae of ideal lumbar lordosis determined by individual pelvic incidence and thoracic kyphosis in asymptomatic adults.

BACKGROUND: The precise prediction of ideal lumbar lordosis (LL) has become increasingly important in clinical practice. The aim of this study was to explore the regulatory mechanisms of sagittal spinopelvic alignment and to predict ideal LL based on individual pelvic incidence (PI) and thoracic kyphosis (TK) parameters in asymptomatic adults. METHODS: A total of 233 asymptomatic subjects older than 18 years were consecutively enrolled in our study between April 2017 and December 2019. A full-spine, standing X-ray was performed for each subject. The following parameters were measured in the sagittal plane: the apex of lumbar lordosis (LLA), the distance between the plumb line of the lumbar apex (LAPL) and the gravity plumb line, the inflection point (IP), LL, the upper arc and lower arc of lumbar lordosis (LLUA and LLLA, respectively), PI and TK. Stepwise multiple linear regressions were conducted, and the statistical significance level was P < 0.05. RESULTS: Both PI and TK were two important predictive variables for LLA, LAPL, IP and LL. In addition, the LLUA was mainly explained by TK, while the LLLA was explained by PI. The corresponding predictive models are listed as follows: LLA = 17.110 - 0.040∗PI + 0.023∗TK (R2 = 0.380), LAPL = 31.296 + 0.467∗PI - 0.126∗TK (R2 = 0.309), IP = 10.437 + 0.091∗TK - 0.029∗PI (R2 = 0.227), LL = 2.035 + 0.618∗PI + 0.430∗TK (R2 = 0.595), LLUA = 0.893 + 0.418∗TK (R2 = 0.598), LLLA = 3.543 + 0.576∗PI (R2 = 0.433). CONCLUSION: The specific sagittal lumbar profile should be regulated by both pelvic and thoracic morphology. Such predictive models for lumbar parameters determined by individual PI and TK parameters have been established, which are meaningful for surgeons to better understand the regulatory mechanisms of sagittal spinopelvic alignment and reconstruct a satisfactory lumbar alignment.

Predictive model of global tilt (GT) determined by individual thoracic kyphosis, lumbar lordosis and pelvic incidence in the human degenerative spine.

PURPOSE: Previous studies only investigated the simple linear relationships of global tilt (GT) with thoracic kyphosis (TK), lumbar lordosis (LL) and pelvic incidence (PI). This study aimed to establish multiple linear regressions of GT based on individual TK, LL and PI in patients with degenerative spines. METHODS: Four hundred sixty-nine adult patients aged older than 35 years with various degenerative spinal diseases were enrolled in this two-centre study between January 2017 and December 2020. Full-spine X-rays were performed for all the subjects in a standing position. The following regional and global parameters were measured in the sagittal plane: TK, LL, PI, pelvic tilt (PT), sagittal vertical axis (SVA) and GT. The correlations of the GT, PT and SVA with the TK, LL and PI were analysed, and then multiple linear regressions were constructed. RESULTS: GT was statistically correlated with TK, LL and PI. Additionally, TK, LL and PI were significant predictors for the GT, PT and SVA models. The relevant predictive formulae were as follows: GT = -9.60 + 1.09*PI + 0.89*LL + 0.42*TK (R2 = 0.935), PT = -4.49 + 0.81*PI + 0.56*LL + 0.24*TK (R2 = 0.792) and SVA = -25.68 + 2.98*LL + 2.37*PI + 1.67*TK (R2 = 0.416). CONCLUSION: The specific sagittal spinopelvic morphology, evaluated by GT parameters, should be determined by individual TK, LL and PI values in the degenerative spine. Surgeons can utilize such predictive models to better understand the degenerative evolution of sagittal alignment and recognize the relationships between regional parameters and global sagittal alignment to customize a precise correction strategy.

Patient characteristics and 6-month dose of basal insulin associated with HbA1c achievement <7.0% in Chinese people with type 2 diabetes: results from the Observational Registry of Basal Insulin Treatment (ORBIT).

BACKGROUND: The efficacy of basal insulin (BI) for adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) has been well documented by randomized clinical trials. This post hoc analysis of the Observational Registry of Basal Insulin Treatment (ORBIT) study was performed to explore the 6-month dose of BI used in insulin-naïve T2DM patients achieving HbA1c target (<7%) and determine the patient characteristics that affect the 6-month dose of BI in the setting of real-world clinics in China. METHODS: This multicenter observational registry screened 19 894 adult T2DM patients with inadequately controlled hyperglycemia and treated with oral antidiabetic drugs (OADs) in China. Of these patients, 5191 who continued to receive BI after 6 months and achieved HbA1c target were analyzed. Patient characteristics including age, body weight, fasting plasma glucose (FPG), use of OADs, insulin (type and dose), and glycemic control were recorded at baseline and 6-month follow-ups. RESULTS: The 6-month dose of BI needed for effective glycemic control was 0.20 ± 0.08 U/kg/day. High body mass index, high FPG, young age, longer duration of diabetes or OAD treatment, a greater number of OADs at baseline, and allocation to detemir and glargine were significant independent predictors for high dose of BI at 6 months. CONCLUSIONS: This post hoc analysis of the ORBIT registry provides key information on the 6-month dose of BI needed for effective glycemic control in Chinese T2DM patients. Furthermore, it identified crucial patient characteristics that are significant determinants of the dose of BI in a real-world setting.

Greater macrovascular and microvascular morbidity from type 2 diabetes in northern compared with southern China: A cross-sectional study.

AIMS/INTRODUCTION: There are substantial differences in genes, diet, culture and environment between the northern and southern Chinese populations, which might influence treatment strategy and screening policy. We studied the differences in type 2 diabetes and diabetic complications between northern and southern China. MATERIALS AND METHODS: We carried out a cross-sectional survey using data from the China Cardiometabolic Registries on blood pressure, blood lipids and blood glucose in 25,398 Chinese type 2 diabetes patients. Macrovascular, microvascular and other complications were collected by self-report or medical records, and then divided into the northern and southern groups by the boundary of the Yangtze River. RESULTS: Northern patients were younger, and had heavier weight, greater body mass index and waist circumference, higher blood pressure, higher total cholesterol, higher low-density lipoprotein cholesterol, and higher hemoglobin A1C. The prevalence of cardiovascular, cerebrovascular and macrovascular complications were 1.76-fold, 1.24-fold and 1.47-fold more in northern than that in southern Chinese patients. In addition, the prevalence of diabetic nephropathy, retinopathy, neuropathy and microvascular complications in northern Chinese patients also increased. When stratified by age, the difference in both cardiovascular disease and ischemic stroke morbidity became significant, even in the 35-44 years age group. CONCLUSIONS: More macrovascular and microvascular complications were found in northern compared with southern patients, and the largest difference also appeared in the younger age groups <55 years, which might be meaningful to a screening and treatment strategy according to geographic differences.

Correlations between the inflection point and spinal sagittal alignment in asymptomatic adults.

PURPOSE: The purposes of this study were to analyse the correlations between the inflection point (IP) and spinal sagittal parameters and to establish the corresponding linear regressions in asymptomatic adults. METHODS: A total of 205 asymptomatic subjects older than 18 years were recruited between April 2017 and September 2019. A full-spine, standing X-ray was collected for each subject. The following parameters were documented: the IP, the apices of thoracic kyphosis (TKA) and lumbar lordosis (LLA), the distance between the plumb line of the thoracic apex (TAPL) or lumbar apex (LAPL) and gravity plumb line, thoracic kyphosis (TK), lumbar lordosis (LL) and the upper arc and the lower arc of lumbar lordosis (LLUA and LLLA, respectively). The correlations between the IP and the above parameters and between the thoracic and lumbar parameters were analysed. The level of significance was P < 0.05. RESULTS: The IP was statistically correlated with age (rs = 0.327), the TKA (rs = 0.639), the TAPL (rs = 0.338), TK (rs = 0.391), the LLA (rs = 0.545), the LAPL (rs = - 0.383), the LLUA (rs = 0.371) and the LLLA (rs = - 0.145) but was not linked with LL (rs = 0.118). In addition, there were relationships between the TKA and LLA (rs = 0.397), the TAPL and LAPL (rs = - 0.357), TK and LL (rs = 0.529), TK and the LLUA (rs = 0.742) and TK and the LLLA (rs = 0.148). CONCLUSION: The IP was significantly related to spinal sagittal alignment in asymptomatic adults. Moreover, predictive formulae for sagittal parameters as a function of the IP were developed, which are helpful for surgeons in comprehending the regulatory mechanisms of spinal sagittal alignment and designing an ideal therapeutic plan. These slides can be retrieved under Electronic Supplementary Material.

Evaluation of effectiveness of treatment paradigm for newly diagnosed type 2 diabetes patients in Chin: A nationwide prospective cohort study.

AIMS/INTRODUCTION: Data of nationwide glycemic control and hypoglycemic treatment patterns in newly diagnosed type 2 diabetes patients in China are absent. The aim of this study was to assess the evolution of treatment patterns for newly diagnosed type 2 diabetes patients and the clinical outcomes during 12-month follow up. MATERIALS AND METHODS: This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes for <6 months were enrolled. Glycated hemoglobin A1c (HbA1c) levels and hypoglycemic treatment patterns were collected at baseline and at every 3 months of follow up. RESULTS: A total of 79 hospitals were recruited, consisting of 5,770 participants. The mean HbA1c was 8.4 ± 2.5% at baseline, and decreased to 6.7 ± 1.2% at 12 months with 68.5% of patients achieving HbA1c <7%. At baseline, 44.6% of the patients were without hypoglycemic medications, 37.7% had oral hypoglycemic agents and 17.7% received insulin treatment. Determinants of change in HbA1c were treatment patterns, comorbidities, baseline characteristics such as obesity and smoking, regions, and tiers of hospitals. Associated factors with treatment alterations were time of follow up, treatment patterns, patient-reported reasons such as the economic factors and poor efficacy. CONCLUSIONS: In newly diagnosed type 2 diabetes patients, compared with patients without medications, patients with one oral hypoglycemic agent had higher possibilities of reaching glycemic control, whereas patients using insulin had lower possibilities of reaching the target. Factors associated with change in HbA1c and treatment alterations were also revealed.

Correlation between the apex of lumbar lordosis and pelvic incidence in asymptomatic adult.

PURPOSE: The objective of this study was to test the correlation between the apex of lumbar lordosis (LLA) and pelvic incidence (PI) in asymptomatic adults, and to establish predictive formulae based on the PI to obtain the reference values of lumbar sagittal parameters. METHODS: A cohort of 183 asymptomatic volunteers older than 18 years was enrolled in this study between April 2017 and May 2019. A full-spine, standing X-ray was taken for each subject. The following parameters in the sagittal plane were measured: the LLA, the distance between the plumb line of the lumbar apex (LAPL) and gravity plumb line, lumbar lordosis (LL), the upper arc of lumbar lordosis (LLUA), the lower arc of lumbar lordosis (LLLA) and the PI. The correlations between lumbar parameters and PI were analysed, and simple linear regressions were simultaneously constructed. The statistical significance level was P < 0.05. RESULTS: The PI was statistically correlated with the LLA (rs = - 0.595, P < 0.001), LAPL (rs = 0.503, P < 0.001), LL (rs = 0.605, P < 0.001), LLUA (r = 0.354, P < 0.001) and the LLLA (r = 0.658, P < 0.001). The corresponding regression formulae were as follows: LLA = - 0.042*PI + 6.134 (R2 = 0.306), LAPL = 0.448*PI + 26.570 (R2 = 0.279), LL = 0.888*PI - 2.667 (R2 = 0.370), LLUA = 0.272*PI - 2.297 (R2 = 0.126) and LLLA = 0.607*PI + 0.177 (R2 = 0.433). CONCLUSION: The PI has strong correlations with the LLA, LAPL, LL, LLUA and LLLA, which demonstrates that the specific lumbar shape can be affected by the pelvic morphology. Moreover, predictive models for ideal lumbar sagittal parameters based on the PI have been developed, contributing to the design of precise and individualized preoperative plans. These slides can be retrieved under Electronic Supplementary Material.

Characteristics of Newly Diagnosed Type 2 Diabetes in Chinese Older Adults: A National Prospective Cohort Study.

AIM: To investigate the metabolic profiles of newly diagnosed type 2 diabetes (NEW2D) in Chinese older adults (≥65 years) and assess the proportion of patients who achieved the targeted goals of blood glucose, blood pressure, and blood lipid. METHODS: NEW2D study was an observational, longitudinal, prospective cohort study involving patients who were diagnosed with type 2 diabetes (T2D) within the past 6 months and had a follow-up of 12 months. Participants were divided into younger NEW2D group (aged 20-65 years old) and older NEW2D group (aged ≥65 years old) according to age of diabetes onset. The baseline metabolic profiles were compared and the proportion of patients achieving adequate control of blood glucose, blood pressure, and blood lipids in reference to target goals were assessed during treatment. RESULTS: The older NEW2D (n = 1362) had a lower BMI, HbA1c%, diastolic blood pressure, triglyceride, low-density lipoprotein cholesterol (LDL-C), and total cholesterol, higher systolic blood pressure, and high-density lipoprotein cholesterol levels at baseline. 47.8%, 66.7%, and 39.4% reached the target of HbA1c < 7.0%, BP < 140/90 mmHg, and LDL - C < 2.6 mmol/L, respectively. After 12 months, the proportion achieving above three targets increased to 70.2%, 76.1%, and 47.5%, respectively. The proportions of patients achieving three combined therapeutic targets doubled from 13.5% to 26.7%. CONCLUSION: The older NEW2D patients have special metabolic profiles compared with younger patients. The control of cardiovascular disease risk factors was suboptimal in older adults with type 2 diabetes.

The risk factors of glycemic control, blood pressure control, lipid control in Chinese patients with newly diagnosed type 2 diabetes _ A nationwide prospective cohort study.

Nationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This study was registered at www.clinicaltrials.gov (NCT01525693). A total of 5770 participants from 79 hospitals across six geographic regions of China were recruited. After 12 months of treatment, 68.5% of these patients achieved HbA1c <7.0%; 83.7% reached BP <140/90 mmHg; 48.2% met low density lipoprotein cholesterol (LDL-c) <2.6 mmol/L; and 29.5% of patients reached the combined three therapeutic targets. Compared to those patients with baseline HbA1c <7.0%, patients with baseline HbA1c ≥7.0% had higher failure rate to reach glycemic control (relative risk (RR) = 2.04, p < 0.001), BP control (RR = 1.21, p < 0.001) and LDL-c control (RR = 1.11, p < 0.001). Obese patients had higher possibilities of failure in glucose control (RR = 1.05, p = 0.004), BP control (RR = 1.62, p < 0.001) and lipid control (RR = 1.09, p = 0.001) than patients with normal weight. The active smokers were more likely to fail in glycemic control than non-smokers (RR = 1.06, p = 0.002), and patients with physical activities were less likely to fail in lipid control than patients without exercises (RR = 0.93, p = 0.008). This study outlined the burdens of glycemic control, blood pressure control, lipid control in newly diagnosed type 2 diabetic patients in China, identified gaps in the quality of care and risk-factor control and revealed the factors influencing these gaps.

Targeting allosteric site of AKT by 5,7-dimethoxy-1,4-phenanthrenequinone suppresses neutrophilic inflammation.

BACKGROUND: Acute lung injury (ALI) is a severe life-threatening inflammatory disease. Neutrophil activation is a major pathogenic factor in ALI. Protein kinase B (PKB)/AKT regulates diverse cellular responses, but the significance in neutrophilic inflammation and ALI remains unknown. METHODS: Human neutrophils and neutrophil-like differentiated HL-60 (dHL-60) cells were used to examine the anti-inflammatory effects of 5,7-dimethoxy-1,4-phenanthrenequinone (CLLV-1). The therapeutic potential of CLLV-1 was determined in a mouse model of lipopolysaccharide (LPS)-induced ALI. FINDINGS: CLLV-1 inhibited respiratory burst, degranulation, adhesion, and chemotaxis in human neutrophils and dHL-60 cells. CLLV-1 inhibited the phosphorylation of AKT (Thr308 and Ser473), but not of ERK, JNK, or p38. Furthermore, CLLV-1 blocked AKT activity and covalently reacted with AKT Cys310 in vitro. The AKT309-313 peptide-CLLV-1 adducts were determined by NMR or mass spectrometry assay. The alkylation agent-conjugated AKT (reduced form) level was also inhibited by CLLV-1. Significantly, CLLV-1 ameliorated LPS-induced ALI, neutrophil infiltration, and AKT activation in mice. INTERPRETATION: Our results identify CLLV-1 as a covalent allosteric AKT inhibitor by targeting AKT Cys310. CLLV-1 shows potent anti-inflammatory activity in human neutrophils and LPS-induced mouse ALI. Our findings provide a mechanistic framework for redox modification of AKT that may serve as a novel pharmacological target to alleviate neutrophilic inflammation.

Kinetic of bone turnover markers after osteoporotic vertebral compression fractures in postmenopausal female.

BACKGROUND: Osteoporotic fracture occurs mostly at the spine, in which the commonest one is vertebral compression fracture. Bone turnover markers (BTMs) can be applied to assess bone formation and resorption activity. Nevertheless, there are few reports on BTMs changes after osteoporotic vertebral compression fracture. The aim of this study is to investigate the kinetics of bone turnover markers after osteoporotic vertebral compression fractures in postmenopausal female. METHODS: Three hundred nine postmenopausal female patients with osteoporotic vertebral compression fractures were included in the study. Fasting blood samples were obtained to analyze the serum concentration of bone turnover markers including osteocalcin (OC), ß-isomerized type I collagen amino-terminal peptide (ß-CTX), alkaline phosphatase (ALP), type I procollagen amino-terminal peptides (PINP), calcium, and phosphorus. According to periods long after vertebral fracture, all the cases were divided into seven phases: phase 1 (within 3 days), phase 2 (3 days to 1 week), phase 3 (1 to 2 weeks), phase 4 (2 to 4 weeks), phase 5 (4 to 12 weeks), phase 6 (12 to 24 weeks), and phase 7 (24 weeks to 1 year). Comparisons among the phases and kinetics during the phases were conducted. RESULTS: All the kinds of BTM's serum concentration began to increase within 3 days after vertebral fracture in phase 1. Osteocalcin and ß-CTX had two peaks, the first one in phase 2 (21.4 ± 6.0 ng/ml and 0.72 ± 0.17 ng/ml, respectively) and the second in phase 6 (25.8 ± 7.5 ng/ml and 0.89 ± 0.23 ng/ml, respectively). The peak of ALP arrived in phase 4 at the value of 123.9 ± 25.7 U/L. PINP reached its peak value (69.50 ± 16.82 ng/ml) in phase 6. Serum phosphorus arrived at its first peak (1.21 ± 0.13 mmol/L) in phase 2 and the second peak (1.23 ± 0.13 mmol/L) in phase 4. Serum calcium reached the first peak (2.30 ± 0.07 mmol/L) in phase 3 and the second peak (2.34 ± 0.08 mmol/L) in phase 5. CONCLUSION: The time-dependent variations of BTMs based on the fracture healing process of inflammation, regeneration, and remodeling occur after vertebral fracture. Kinetics of BTMs after vertebral fracture as well as the reference value at each period were established in the present study. It is helpful to assess vertebral fracture healing process according to the kinetics of BTMs.