Ultrasound-guided Hydrogel Injection Provides Better Therapeutic Effects After Hand Tendon Surgery Than Intraoperative Injection: A Randomized Controlled Trial.

BACKGROUND: Hydrogels are used to provide a barrier against peritendinous adhesion formation, but when implanted intraoperatively, they degrade rapidly and aggravate early inflammatory pain. It is uncertain whether clinical efficacy can be improved by avoiding the inflammatory phase when hydrogels are delivered during adhesion formation. QUESTIONS/PURPOSES: (1) Compared with intraoperative hydrogel application, does ultrasound-guided postoperative application result in better total active motion (TAM) at 12 months after tendon injury? (2) Does ultrasound-guided postoperative application of hydrogels result in lower pain, better function, and better satisfaction? METHODS: This open-label, prospective, single-center, randomized controlled trial was conducted by reparative and reconstructive surgeons at the National Orthopedics Clinical Medical Center, Shanghai, People's Republic of China. Between May 2021 and December 2022, 53% (168 of 317) of patients who met our inclusion criteria were recruited, and 47% (149 of 317) of patients were excluded because of the exclusion criteria. Finally, 84 patients were randomized to the postoperative group to receive ultrasound-guided carboxymethyl chitosan (CMC) hydrogel delayed injection, and 84 patients were randomized to the intraoperative group to receive CMC hydrogel intraoperative application. Another 8% (7 of 84) of patients in the postoperative group and 10% (8 of 84) of patients in the intraoperative group were lost before the minimum study follow-up time of 1 year or had incomplete datasets, leaving 91% (153 of 168) of patients with data for analysis. Data on outcome events were analyzed according to the intention-to-treat principle, which included all patients who underwent randomization. Follow-up visits were completed at 3 weeks, 6 weeks, 3 months, 6 months, and 12 months after tendon repair. The primary outcome was TAM (ie, the sum of the degrees of active metacarpophalangeal joint, proximal interphalangeal joint, and distal interphalangeal joint flexion less the degrees from full extension; minimum clinically important difference [MCID] 20°) at 12 months. Secondary outcomes included pain (measured with a VAS; range 0 to 10, a higher score indicating worse pain; MCID 0.6), Michigan Hand Outcomes Questionnaire activities of daily living (MHQ-ADL) score (range 0 to 100, a higher score indicating better outcomes; MCID 10.1), and MHQ satisfaction (MHQ-SAT) score (range 0 to 100, a higher score indicating better outcomes; MCID 33.0). RESULTS: At 12 months, the ultrasound-guided postoperative injection group had improved TAM (intraoperative 189° [95% CI 179° to 199°] versus postoperative 209° [95% CI 199° to 219°], mean difference 20° [95% CI 6° to 35°]; p = 0.006; the mean difference in the primary outcome fulfilled the MCID value at all time points). At 6 weeks, we found no clinically important difference in VAS pain scores among groups (intraoperative mean ± SD 2.0 ± 1.0 versus postoperative 1.7 ± 1.0, mean difference 0.3 [95% CI 0.1 to 0.7]; p = 0.02); however, at 3 weeks, the VAS pain scores showed clinically important difference among groups (3.6 ± 1.4 versus 2.9 ± 1.2, mean difference 0.7 [95% CI 0.3 to 1.1]; p = 0.001). At 3 months, the ultrasound-guided postoperative injection group had higher MHQ-ADL scores (intraoperative 62 ± 10 versus postoperative 75 ± 10, mean difference 13 [95% CI 11 to 17]; p < 0.001), and the mean difference of MHQ-ADL scores reached the MCID value at all time points. At 3 months, there was no clinically important difference in MHQ-SAT scores between groups (intraoperative 62 ± 8 versus postoperative 70 ± 8, mean difference 8 [95% CI 6 to 11]; p < 0.001). CONCLUSION: Compared with intraoperative CMC hydrogel injection, postoperative ultrasound-guided injection improved the TAM and function of the affected limb, showed a short-term pain control effect, and did not increase the risk of complications. Clinical trials are needed to confirm the safety and efficacy of ultrasound-guided postoperative injection of CMC hydrogels and to determine the most effective dose and the health and economic benefits of treatment. LEVEL OF EVIDENCE: Level I, therapeutic study.

Development of a risk-predicting score for hip preservation with bone grafting therapy for osteonecrosis.

Identification and differentiation of appropriate indications on hip preserving with bone grafting therapy remains a crucial challenge in the treatment of osteonecrosis of the femoral head (ONFH). A prospective cohort study on bone grafting therapy for ONFH aimed to evaluate hip survival rates, and to establish a risk scoring derived from potential risk factors (multivariable model) for hip preservation. Eight variables were identified to be strongly correlated with a decreased rate of hip survival post-therapy, and a comprehensive risk scoring was developed for predicting hip-preservation outcomes. The C-index stood at 0.72, and the areas under the receiver operating characteristics for the risk score's 5- and 10-year hip failure event predictions were 0.74 and 0.72, respectively. This risk score outperforms conventional methods in forecasting hip preservation. Bone grafting shows sustained benefits in treating ONFH when applied under the right indications. Furthermore, the risk scoring proves valuable as a decision-making tool, facilitating risk stratification for ONFH treatments in future.

[Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort].

Objective: To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Methods: Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. Results: The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. Conclusion: The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Development of a Conjugation-Based Genome Editing System in an Undomesticated Bacillus subtilis Strain for Poly-γ-glutamic Acid Production with Diverse Molecular Masses.

Poly-γ-glutamic acid (γ-PGA) is a biodegradable polymer produced by microorganisms. Biosynthesizing γ-PGA with diverse molecular masses (Mw) is an urgent industrial technical problem to be solved. Bacillus subtilis KH2, a high-Mw γ-PGA producer, is an ideal candidate for de novo production of γ-PGA with diverse Mw values. However, the inability to transfer DNA to this strain has limited its industrial use. In this study, a conjugation-based genetic operating system was developed in strain KH2. This system enabled us to modify the promoter of γ-PGA hydrolase PgdS in strain KH2 chromosome to de novo biosynthesize γ-PGA with diverse Mws. The conjugation efficiency was improved to 1.23 × 10-4 by establishing a plasmid replicon sharing strategy. A further increase to 3.15 × 10-3 was achieved after knocking out two restriction endonucleases. To demonstrate the potential of our newly established system, the pgdS promoter was replaced by different phase-dependent promoters. A series of strains producing γ-PGA with specific Mws of 411.73, 1356.80, 2233.30, and 2411.87 kDa, respectively, were obtained. The maximum yield of γ-PGA was 23.28 g/L. Therefore, we have successfully constructed ideal candidate strains for efficient γ-PGA production with a specific Mw value, which provides an important research basis for sustainable production of desirable γ-PGA.

In-hospital waiting time to surgery and functional outcomes in geriatric hip fractures: a directed acyclic graph-based preplanned analysis from a prospective multicenter cohort study.

BACKGROUND: The early recovery of hip function after hip fracture surgery values more attention, especially for patients with delayed surgery of longer than 48 h. We aim to evaluate the associations of in-hospital surgical waiting time with the functional outcomes [Harris Hip Score (HHS), Parker Mobility Score (PMS), and EuroQol 5 dimensions VAS (visual analogue scale) score (EQ-5D VAS)] in elderly patients who sustained hip fractures. MATERIALS AND METHODS: Data on sociodemographic and clinical factors were prospectively collected using a multicenter hip fracture registry system. Participants in the cohort underwent a 12-month follow-up investigation. After adjusting potential confounders identified by the directed acyclic graphs, the associations between surgical waiting time longer than 48 h and functional outcomes were estimated by log-binomial regression and multivariable linear regression models with generalized estimating equations. RESULTS: Of 863 survival participants with available functional data at 12 months after surgery, an increased risk was obtained from receiving surgery after 48 h and the poor functional outcomes (HHS<80: relative risk (RR)=1.56, 95% CI: 1.00-2.51; PMS<7: RR=1.49, 95% CI: 1.13-2.01; EQ-5D VAS<80: RR=1.97, 95% CI: 1.57-2.47). In-hospital waiting time greater than 48 h were time-invariantly associated with lower PMS during recovery (-0.44 units 95% CI: -0.70 to -0.18). In addition, delayed surgery was time-varying associated with HHS and EQ-5D VAS. CONCLUSIONS: The associations between in-hospital waiting time and postoperative functional score suggest that delayed surgery can lead to poor functional outcomes, especially in patients waiting longer than 72 h from injury. Delayed surgery mainly impacted hip function and mobility recovery with a slower speed in early recovery of the first 3 months. More attention should be paid to mechanisms behind the associations between delayed surgery on general healthy status.

Integrated Rabies Surveillance - Hunan Province, China, 2020.

Introduction: The objective of this paper was to assess the epidemiology of rabies in Hunan Province, analyze the associated factors, understand the status of prevention and treatment after rabies exposure, evaluate the effectiveness of prevention and treatment, and provide a scientific basis for formulating effective prevention and control measures. Methods: The surveillance data of rabies in Hunan Province in 2020 were collected and analyzed by descriptive epidemiological method. Results: In 2020, a total of 59 cases of rabies were reported in Hunan Province, with an incidence rate of 0.09/100,000. Overall, 42 cases (71.19%) were due to animal bites and 43 cases (72.88%) were of grade III. The proportion of hand and combined injury of hand was the highest (40.68%). A total of 603,261 cases of rabies exposure were reported from the rabies post-exposure prophylaxis (PEP) clinic in Hunan Province. Dogs were the main animal causing injuries, accounting for 74.21%. Only 83,418 (13.84%) of the animals had a clear immune history, and a total of 11 dog attacks were reported in Hunan Province. The average immunity rate of dogs in the whole province was 30.98%. In 2020, 554 dogs were sampled in the whole province; 20 of them were positive for a positivity rate of 3.61%. Conclusions: Rabies in Hunan Province in 2020 had a relatively low prevalence. Failure to treat wounds, immunoglobulin injections, and vaccination after exposure were the main causes of rabies. Therefore, post-exposure management of rabies should be further strengthened to reduce the risk of rabies for high-risk populations.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Efficient molasses utilization for low-molecular-weight poly-γ-glutamic acid production using a novel Bacillus subtilis stain.

BACKGROUND: Poly-γ-glutamic acid (γ-PGA) is a biopolymer and has various applications based on its biocompatibility, non-toxicity, and edibility. Low-molecular-weight (Mw)-γ-PGA has promising applications in agriculture and pharmaceuticals. It is traditionally produced by enzymatic hydrolysis. Cost-effective bioproduction of low-Mw-γ-PGA is essential for commercial application of γ-PGA. RESULTS: Bacillus subtilis 242 is a newly isolated low-Mw-γ-PGA-producing strain. To develop cost-effective production of γ-PGA using this newly isolated strain, cane molasses and corn steep liquor were used to produce γ-PGA. The concentration of cane molasses was optimized and 100 g/L cane molasses resulted in high γ-PGA production. The effects of yeast extract and corn steep liquor on γ-PGA yield were investigated. High concentration of γ-PGA was obtained in the medium with corn steep liquor. A concentration of 32.14 g/L γ-PGA was achieved in fed-batch fermentation, with a productivity of 0.67 g/L/h and a percentage yield (gγ-PGA/gglutamate) of 106.39%. The Mw of γ-PGA was 27.99 kDa. CONCLUSION: This study demonstrated the potential application of B. subtilis 242 for cost-effective production of low-Mw-γ-PGA from cane molasses.

The Impact of COVID-19 on SARSCoV-2-Negative Elderly Patients with Hip Fractures: A Single-Center Retrospective Study from Shanghai, China.

Purpose: Coronavirus disease 2019 (COVID-19) has brought an unprecedented change in wellbeing globally. The spread of the pandemic reportedly reduced the incidence of activity-related trauma, while that of fragility fractures remained stable. Here, we aimed to identify the risk factors associated with the prognosis of SARS-CoV-2 negative elderly patients with hip fractures. Patients and Methods: This retrospective study included elderly patients with hip fractures between 1st January and 9th May during the COVID-19 pandemic (Experiment group) and the same period from 2017 to 2019 (Control group). Perioperative mortality, complications, and functional recovery were compared between two groups of different time frame in the total cohort and patients who received surgical treatment. Multiple linear regression was carried out to identify the risk factors influencing the prognosis of COVID-negative elderly patients with hip fractures. Results: The proportion of patients with admission time less than 24 hours and the 6-month postoperative Parker score were significantly decreased during COVID-19 compared with the pre-COVID-19 period (p < 0.001). Multiple linear regression demonstrated that TTA (defined as time from injury to admission), rehabilitation after discharge and outpatient follow-up were associated with the 6-month Parker score in the total population (p < 0.001) and in patients who received surgical treatment (p < 0.001). Conclusion: Elderly patients with hip fractures had a poorer prognosis in epidemic period despite being COVID-19 negative. Factors including timely admission, postoperative follow-up, and rehabilitation could optimize safety and significantly improve the prognosis of elderly COVID-19 negative patients with hip fractures, even during a pandemic.

Risk factors for preterm birth: a prospective cohort study. / æ—©äº§å±é™©å› ç´ çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To investigate the incidence of preterm birth and risk factors for preterm birth. METHODS: A prospective cohort study was performed for the pregnant women in early pregnancy and their spouses, who underwent prenatal examination for the first time in Hunan Provincial Maternal and Child Health Care Hospital from May 2014 to December 2016 and decided to be hospitalized for delivery. A questionnaire survey was performed to collect exposure information possibly related to preterm birth. The hospital's medical record system was used for information verification and to record the pregnancy outcome. A multivariate logistic regression analysis was used to investigate the risk factors for preterm birth. RESULTS: A total of 6 764 pregnant women with complete data were included, and the incidence rate of preterm birth was 17.09%. The multivariate logistic regression analysis showed that a history of adverse pregnancy outcomes, eating areca nut before pregnancy, a history of pregnancy complications, a history of hepatitis, no folate supplementation during pregnancy, medication during pregnancy, active smoking and passive smoking during pregnancy, drinking during pregnancy, unbalanced diet during pregnancy, high-intensity physical activity during pregnancy, and natural conception after treatment of infertility or assisted conception as the way of conception were risk factors for preterm birth (P<0.05). Additionally, the pregnant women whose spouses were older, had a higher body mass index or smoked had an increased risk for preterm birth (P<0.05). A higher level of education of pregnant women or their spouses and lower gravidity were protective factors against preterm birth (P<0.05). CONCLUSIONS: There are many risk factors for preterm birth. Special attention should be paid to the life behaviors of pregnant women during pregnancy, and health education should be strengthened for pregnant women and their spouses to develop good living habits and reduce the incidence of preterm births.

Analysis of Combined Indicators for Risk of Osteoporotic Hip Fracture in Elderly Women.

OBJECTIVE: To compare the accuracy of combined independent risk factors in assessing the risk of hip fractures in elderly women. METHODS: Ninety elderly females who sustained hip fractures (including femoral neck fractures and intertrochanteric fractures) and 110 female outpatients without a hip fracture were included in our cross-sectional study from 24 November 2017 to 20 May 2019. The age of subjects in the present study was ≥65 years, with the mean age of 78.73 ± 7.77 and 78.09 ± 5.03 years for women with and without elderly hip fractures, respectively. Bone mineral density (BMD), Beta-carboxy terminal telopeptide (ß-CTX), N-terminal/mid region (N-MID), and 25(OH)D levels were analyzed. A novel evaluation model was established to evaluate combined indicators in assessing hip fractures in elderly women. RESULTS: Compared with the control group, taller height (155.68 ± 6.40 vs 150.97 ± 6.23, P < 0.01), higher levels of ß-CTX (525.91 ± 307.38 vs 330.94 ± 289.71, P < 0.01), and lower levels of total hip BMD (0.662 ± 0.117 vs 0.699 ± 0.111, P = 0.022), femoral neck BMD (0.598 ± 0.106 vs 0.637 ± 0.100, P = 0.009), and 25(OH)D (15.67 ± 7.23 vs 29.53 ± 10.57, P < 0.01) were found in the facture group. After adjustment for confounding factors, logistic regression analysis revealed that 25(OH)D (adjusted OR 0.837 [95% CI 0.790-0.886]; P < 0.01), femoral neck BMD (adjusted OR 0.009 [95% CI 0.000-0.969]; P = 0.048) and height (adjusted OR 1.207 [95% CI 1.116-1.306]; P < 0.01) remained risk factors for hip fractures in elderly women. Then a model including independent risk factors was established. A DeLong test showed the area under the receiver operator characteristic (ROC) (Area under the curve [AUC]) of 25(OH)D was significantly greater than that for femoral neck BMD (P < 0.01) and height (P < 0.01). The AUC of model including 25(OH)D and height was significantly greater than that of other combinations (P < 0.01). CONCLUSION: 25(OH)D, femoral neck BMD and height were associated with the occurrence of hip fractures in elderly women even after adjustment for confounding factors, and a model including 25(OH)D and height could provide better associated power than other combinations in the assessment of elderly hip fractures.

Associations between glucocorticoids, antiphospholipid antibodies and femur head necrosis in patients with SLE: a directed acyclic graph-based multicentre study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE. METHODS: We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis. RESULTS: Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0-1.1; GC therapy duration (3-5 years: aOR 3.3, 95% CI 1.4-7.8; >5 years: aOR 8.0, 95% CI 3.3-19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9-10.1); positive aPLs (aOR 2.8, 95% CI 1.4-5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4-19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82-0.94). CONCLUSION: Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.

The Associations of Serum Vitamin D and Bone Turnover Markers with the Type and Severity of Hip Fractures in Older Women.

PURPOSE: Vitamin D (25[OH]D) status and bone turnover markers (BTMs) are considered important determinants of bone quality, which is associated with the risk of hip fractures, including both femoral neck and intertrochanteric fractures, in older adults; however, the exact relationship of 25(OH)D and BTMs with the type and severity of hip fractures remains unclear and the present study aimed to identify any specific associations. PATIENTS AND METHODS: According to the inclusion and exclusion criteria, 441 older female patients with hip fractures from 2015 to 2020 and 215 women without hip fractures were included in this cross-sectional study. According to Garden and AO/OTA classifications for femoral neck and intertrochanteric fractures, patients were divided into less severe (Garden I and Garden II; 31A1) and more severe (Garden III and Garden IV; 31A2 and 31A3) fracture groups. Levels of the serum osteoblast indicator, N-terminal/mid region (N-MID); the osteoclast indicator, beta-carboxy terminal telopeptide (ß-CTX); and 25(OH)D were analyzed. RESULTS: For patients with less severe fractures, mean 25(OH)D levels were significantly higher than those with more severe fractures (17.67 vs 15.30 ng/mL, p = 0.006). Higher 25(OH)D levels were also observed in patients with less severe intertrochanteric fractures (p = 0.01). After adjustments for confounders, 25(OH)D remained a risk factor for patients with more severe fractures (p = 0.01), particularly those with intertrochanteric fractures (p = 0.011). No significant differences in BTMS were found between patients with less severe and more severe fractures. CONCLUSION: Levels of 25(OH)D were significantly associated with the severity of intertrochanteric, but not femoral neck, fractures. Neither 25(OH)D nor BTMs were associated with the type of hip fracture in older women. Separate consideration of intertrochanteric and femoral neck fractures may be appropriate when investigating the clinical association between 25(OH)D and the severity of hip fractures in older women.

Association between infertility treatment and perinatal depressive symptoms: A meta-analysis of observational studies.

OBJECTIVE: Recent reports have shown a considerable number of couples received infertility treatment, raising new concerns about the association between infertility treatment and perinatal depressive symptoms. However, the conclusions of existing studies were inconsistent. Therefore, we conducted a meta-analysis to determine whether infertility treatment increase the risk of developing perinatal depressive symptoms. METHODS: A systematic literature search was performed in several databases up to July 2018 for relevant articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup and sensitivity analyses were performed to explore possible sources of heterogeneity. RESULTS: Twenty-two studies with a total of 69,201 individuals were included in this study. The pooled OR of the association between infertility treatment and perinatal depressive symptoms was 1.01(95% CI: 0.83, 1.23), with substantial heterogeneity (I2 = 63%, P < .001). However, in subgroup analyses, a significantly positive association between infertility treatment and depressive symptoms was observed only in some Asian countries (six studies), and the pooled OR was 1.73 (95% CI:1.07, 2.81). An inverse association was found in 6-12 months after delivery (OR = 0.56, 95% CI:0.33, 0.96). Sensitivity analyses validated evidence of the robustness of the findings. CONCLUSION: The results show that women who receive infertility treatment do not appear to be at increased risk of significant perinatal depressive symptoms compared with those after spontaneous conception.

Exosomes Secreted from Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Prevent Osteonecrosis of the Femoral Head by Promoting Angiogenesis.

Background: Local ischemia is the main pathological performance in osteonecrosis of the femoral head (ONFH). There is currently no effective therapy to promote angiogenesis in the femoral head. Recent studies revealed that exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSC-Exos) have great therapeutic potential in ischemic tissues, but whether they could promote angiogenesis in ONFH has not been reported, and little is known regarding the underlying mechanism. Methods: iPS-MSC-Exos were intravenously injected to a steroid-induced rat osteonecrosis model. Samples of the femoral head were obtained 3 weeks after all the injections. The effects were assessed by measuring local angiogenesis and bone loss through histological and immunohistochemical (IHC) staining, micro-CT and three-dimensional microangiography. The effects of exosomes on endothelial cells were studied through evaluations of proliferation, migration and tube-forming analyses. The expression levels of angiogenic related PI3K/Akt signaling pathway of endothelial cells were evaluated following stimulation of iPS-MSC-Exos. The promoting effects of exosomes were re-evaluated following blockade of PI3K/Akt. Results: The in vivo study revealed that administration of iPS-MSC-Exos significantly prevented bone loss, and increased microvessel density in the femoral head compared with control group. We found that iPS-MSC-Exos significantly enhanced the proliferation, migration and tube-forming capacities of endothelial cells in vitro. iPS-MSC-Exos could activate PI3K/Akt signaling pathway in endothelial cells. Moreover, the promoting effects of iPS-MSC-Exos were abolished after blockade of PI3K/Akt on endothelial cells. Conclusions: Our findings suggest that transplantation of iPS-MSC-Exos exerts a preventative effect on ONFH by promoting local angiogenesis and preventing bone loss. The promoting effect might be attributed to activation of the PI3K/Akt signaling pathway on endothelial cells. The data provide the first evidence for the potential of iPS-MSC-Exos in treating ONFH.

The temporal effect of platelet-rich plasma on pain and physical function in the treatment of knee osteoarthritis: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Quite a few randomized controlled trials (RCTs) investigating the efficacy of platelet-rich plasma (PRP) for treatment of knee osteoarthritis (OA) have been recently published. Therefore, an updated systematic review was performed to evaluate the temporal effect of PRP on knee pain and physical function. METHODS: Pubmed, Embase, Cochrane library, and Scopus were searched for human RCTs comparing the efficacy and/or safety of PRP infiltration with other intra-articular injections. A descriptive summary and quality assessment were performed for all the studies finally included for analysis. For studies reporting outcomes concerning Western Ontario and McMaster Universities Arthritis Index (WOMAC) or adverse events, a random-effects model was used for data synthesis. RESULTS: Fourteen RCTs comprising 1423 participants were included. The control included saline placebo, HA, ozone, and corticosteroids. The follow-up ranged from 12 weeks to 12 months. Risk of bias assessment showed that 4 studies were considered as moderate risk of bias and 10 as high risk of bias. Compared with control, PRP injections significantly reduced WOMAC pain subscores at 3, 6, and 12 months follow-up (p = 0.02, 0.004, <0.001, respectively); PRP significantly improved WOMAC physical function subscores at 3, 6, and 12 months (p = 0.002, 0.01, <0.001, respectively); PRP also significantly improved total WOMAC scores at 3, 6 and 12 months (all p < 0.001); nonetheless, PRP did not significantly increased the risk of post-injection adverse events (RR, 1.40 [95% CI, 0.80 to 2.45], I 2 = 59%, p = 0.24). CONCLUSIONS: Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and corticosteroids. REVIEW REGISTRATION: PROSPERO CRD42016045410 . Registered 8 August 2016.

Prevalence of clinical anxiety, clinical depression and associated risk factors in chinese young and middle-aged patients with osteonecrosis of the femoral head.

OBJECTIVE: To investigate the prevalence of clinical anxiety and clinical depression in Chinese young and mid-aged patients with osteonecrosis of the femoral head (ONFH) and to analyze their potential risk factors. METHODS: Two hundred and sixteen Chinese patients with ONFH were consecutively enrolled in this cross-sectional study from January 2010 to December 2010. The Zung self-rating anxiety scale (SAS) and the Zung self-rating depression scale (SDS) were used to assess the prevalence of clinical anxiety and clinical depression. An additional questionnaire containing seventeen items of potential risk factors was completed by all patients. Binary logistic regression analysis was employed to reveal potential risk factors of anxiety and depression. RESULTS: The prevalence of clinical anxiety and clinical depression was 20.4% and 21.8% in Chinese young and middle-aged patients with ONFH, respectively. Binary regression analysis showed that independent risk factors correlated with high incidence of clinical anxiety included involved femoral head (OR = 3.168, 95% CI: 1.496 - 6.708) and stages of ONFH (ORIV-V / II = 5.383, 95% CI: 1.664-17.416). Independent risk factors correlated with high incidence of depression included gender (OR = 2.853, 95% CI: 1.467-5.778), comorbid diseases (OR = 4.243, 95% CI: 1.940-9.278) and stages of the disease (OR IV-V/II = 16.963, 95% CI: 4.404-65.331). CONCLUSIONS: Patients with bilateral ONFH are inclined to have clinical anxiety, while female patients and patients with comorbid diseases might tend to get clinical depression. Advanced stages of ONFH are independent risk factors for both clinical anxiety and clinical depression.

Free vascularized fibular grafting for patients receiving postoperative corticosteroids.

Free vascularized fibular grafting (FVFG) is an effective method to treat corticosteroid-induced osteonecrosis of the femoral head (ONFH). Some patients continued to receive maintenance doses of corticosteroids to treat the primary disease postoperatively. This study was performed to evaluate outcomes of FVFG for corticosteroid-induced ONFH in patients who continued to receive corticosteroids postoperatively. The authors retrospectively reviewed the records of 44 patients (78 hips) who had received corticosteroid treatment for their primary disease after FVFG. They were followed up for at least 2 years (mean, 5.6 years). Demographic details, Harris Hip scores, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and radiographic data were collected and analyzed. The mean Harris Hip score for all hips was 70.9±9.9 points before surgery and increased to 84±12.1 points at the latest follow-up. There were also significant increases (P<.05) in physical component summary score and mental component summary score. According to the latest radiographic evaluation, 49 hips (62.8%) appeared improved, 10 hips (12.8%) appeared unchanged, and only 19 hips (24.4%) appeared worse. Seven hips (9%) underwent total hip arthroplasty during the follow-up period. Therefore, the results showed that FVFG was a viable method of treating corticosteroid-induced ONFH in patients who receive maintenance doses of corticosteroids postoperatively.

The effect of postoperative corticosteroid administration on free vascularized fibular grafting for treating osteonecrosis of the femoral head.

Free vascularized fibular grafting (FVFG) has been reported to be an effective method of treating osteonecrosis of the femoral head (ONFH). This study evaluated whether postoperative maintenance doses of corticosteroids had an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH. We retrospectively reviewed the records of 39 patients (67 hips) who had received maintenance doses of corticosteroids following FVFG. This group was matched to a group of patients who had not received corticosteroids treatment after operation. The mean follow-up duration was 5.4 years for the postoperative corticosteroid administration group (PCA group) and 5.0 years for the control group. At the latest follow-up, the average increase in Harris hip score was 11.1 ± 8.7 points for all hips in the PCA group and 12.6 ± 7.4 points for all hips in the control group (P > 0.05). In the PCA group, through radiographic evaluation, 49 hips were improved, 10 hips appeared unchanged, and 8 hips appeared worse. In the control group, 47 hips were improved, 13 hips appeared unchanged, and 7 hips appeared worse. The results suggested that postoperative maintenance doses of corticosteroids do not have an adverse effect on FVFG outcomes in patients with corticosteroid-induced ONFH.

Modified surgical techniques of free vascularized fibular grafting for treatment of the osteonecrosis of femoral head: results from a series of 407 cases.

The goal for treatment of osteonecrosis of the femoral head (ONFH) is to relieve pain, preserve the contour of the femoral head, and delay the need for total hip arthroplasty. The free vascularized fibular grafting (FVFG) has been shown to support the subchondral architecture as well as restore local circulation for the necrotic femoral head in treatment of ONFH. This report aimed to present the clinical results of the use of a modified surgical technique of FVFG for treatment of ONFH. Four hundred and seven patients with 578 hips of ONFH were included. The patients' average age was 36.7 years old (ranging 19-55 years old). The disease was staged from II to V based on the Steinberg classification system. By the modified procedure, the vascularized fibular graft was harvested via a lateral incision with fibular osteotomy prior to the exposure of the vascular pedicle, and the removal of necrotic tissue and inset of graft were performed through an anterior approach. The operative time averaged 90 min for unilateral ONFH (ranging 75-110 min) and 190 min for simultaneous treatment of bilateral ONFH (ranging 160-230 min). The average length of follow-up was 5.0 years (ranging 3-10 years). The complications included one infection in one case, temporary loss of sensation of the thigh in eleven cases, and restricted motion of the great toe in nine cases. The Harris hip score of patients improved from 65.0 to 86.9 on average. Radiographic evaluation showed no changes in 331 hips (57.3%), improvement in 195 hips (33.7%) and necrosis progression in 52 hips (9.0%). Twenty-three hips (4.0%) in 20 patients had total hip arthroplasty during the period. These results show that the modified technique of the use of FVFG for treatment of ONFH yields similar postoperative results in comparison to the traditional method.