ABSTRACT Eravacycline is a broad-spectrum fluorocycline currently approved for complicated intra-abdominal infections (cIAIs). In lung-infection models, it is effective against methicillin-resistant Staphylococcus aureus (MRSA) and tetracycline-resistant MRSA. As such, we aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model to evaluate eravacycline’s pulmonary distribution and kinetics. Data were extracted from a Phase I study ( NCT01989949 ) which assessed the bronchopulmonary disposition of intravenous eravacycline to construct the population PK model that could adequately describe the drug’s pulmonary kinetics. Eravacycline lung PK was best described by a three-compartment model with allometric scaling, with the epithelial lining fluid (ELF) component parameterized as the ELF distribution ratio ( R a t i o = C f r e e , E L F C f r e e , c e n t r a l , unbound concentration in ELF over central compartment). The estimated ELF distribution ratio was 8.26 (95% confidence interval = 6.8–9.8). Besides allometrically scaled weight, no other significant covariate was found. MIC 90 was 0.5 mg/L ( Escherichia coli ), 2 mg/L ( Klebsiella pneumoniae ), 0.5 mg/L ( Acinetobacter baumannii ), and 0.12 mg/L ( S. aureus ). At the approved cIAI dosage or higher (1 mg/kg or 1.5 mg/kg q12h), a PK/PD cutoff value of 2 mg/L was appropriate for E. coli , while a lower value of 1 mg/L was selected for K. pneumoniae , A. baumannii , and S. aureus . For lower doses, the cutoff value was reduced to 0.5 mg/L for K. pneumoniae , A. baumannii , and S. aureus . The study showed eravacycline was widely distributed into the lungs with promising antibacterial efficacy, thus justifying further investigations into its uses for pulmonary infections.

Timely and accurate diagnosis of acute thoracolumbar vertebral compression fractures in X-ray images is critical for initiating prompt and effective treatment, preventing potential neurological damage and long-term disability. Recent advancements in artificial intelligence (AI) have significantly improved medical imaging analysis, providing sophisticated tools to assist clinicians in diagnosing acute thoracolumbar vertebral compression fractures. Nonetheless, detecting these fractures through imaging remains challenging due to the complex overlapping of bony structures in the thoracolumbar region, variability in fracture patterns, and often subtle nature of these injuries. Additionally, the limited availability and sometimes poor quality of medical images further complicate accurate AI-based detection. Addressing these challenges, this study introduces a transfer learning model optimized for recognizing acute thoracolumbar vertebral compression fractures from a small set of low-quality X-ray images. The model starts with a feature extraction model that analyzes multiple texture features of X-ray images. It then employs a Vision Transformer Detector (ViTDet) combined with a faster region-based convolutional neural network (Faster R-CNN) to recognize fractures efficiently. To enhance its performance on small datasets, the model employs a transfer learning approach for training. Extensive experiments with a large dataset of real-world images have shown that this model can effectively recognize acute thoracolumbar vertebral compression fractures from low-quality images, outperforming professionals with specialized knowledge in some cases.

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π–π stacking interaction and a water–magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.

Background: Vancomycin-resistant Enterococcus (VRE) can be carried in the gut for a long period and its carriage status is associated with subsequent infections. This study aimed to investigate the frequency of intestinal VRE carriage in intensive care patients in Beijing. Methods: A multicenter, retrospective cross-sectional study was conducted at six hospitals in Beijing, China. All patients admitted to intensive care units (ICUs) between April 2 and May 1, 2017, were enrolled, and their clinical data were gathered by reviewing electronic medical records. Rectal swabs collected from patients were stored at -80 degrees C in the Institute of Clinical Pharmacology, Peking University First Hospital, and they were selectively cultured for VRE, then the identified strains were analyzed by polymerase chain reaction (PCR) to detect the glycopeptide resistance gene and were characterized by multilocus sequence typing (MLST). Results: Of 148 patients recruited, 46 (31.1%) carried VRE, with the majority (n Z 42) being Enterococcus faecium. In total, 78.3% of the VRE were vanA positive and 15.2% vanM positive, while 6.5% undetected glycopeptide resistance gene. The predominant ST was ST78 (47.6%) followed by ST192 (14.3%), ST555 (9.5%), and ST789 (9.5%). Multivariate analysis showed that factors associated VRE carriage were patients aged >65 years (odds ratio [OR], 3.786; 95% confidence interval [CI], 1.402-10.222) and recent third-generation cephalosporins use (OR, 6.360; 95% CI, 1.873-21.601).

Objectives: This study aimed to investigate the synergistic activity of eravacycline combined with other antimicrobial agents against carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii collected from China. Methods: Sixty carbapenem-resistant strains, including 20 Escherichia coli, 20 Klebsiella pneumoniae, and 20 Acinetobacter baumannii were investigated for the synergy analysis. Imipenem, ceftazidime, cefoperazone-sulbactam, ciprofloxacin, amikacin, and polymyxin B were selected to investigate their efficacy in combination with eravacycline against 60 carbapenem-resistant strains. Minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution method. The efficacy of eravacycline in combination with these agents was determined by the chequerboard method. Results: Antimicrobial susceptibility testing revealed that polymyxin B was most effective against all carbapenem-resistant strains, with resistance rates between 0% and 15%. Eravacycline showed potent activity against E. coli with an 85% susceptibility rate, and may also have activity against K. pneumoniae and A. baumannii with low MIC90 values. The chequerboard method showed that eravacycline-polymyxin B was the most effective combination against E. coli and K. pneumoniae, with more than 30% synergy. The most active combination against A. baumannii was eravacycline-ceftazidime and eravacycline-imipenem, which showed synergy in more than 50% of isolates. Conclusion: Eravacycline combined with beta-lactams or polymyxin B can lead to synergistic effects against clinically common carbapenem-resistant Gram-negative bacteria. The synergistic effects of eravacyclinebased combinations varied in different species. A combination of eravacycline and polymyxin B may be considered for the treatment of carbapenem-resistant E. coli and K. pneumoniae; eravacycline in combination with ceftazidime or a carbapenem antimicrobial may be considered for the treatment of carbapenem-resistant A. baumannii.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Abstract Background The avascular necrosis (AVN) hypothesis of intravertebral cleft (IVC) formation in osteoporotic vertebral fracture (OVCF) has received increasing attention. The aim of this article is to detect whether the segmental artery occlusion causes the IVC following OVCF. Methods Between December 2019 and April 2020, 44 OVCF patients with 46 fracture levels were prospectively enrolled and the vertebral segmental arteries were evaluated by magnetic resonance angiography (MRA). The artery conditions were divided into patent, narrow and occluded. The lesion segmental occlusion rate (LSOR) and the total occlusion rate (TOR) were calculated. The association of segmental artery occlusion and IVC formation was assessed. Results LOSR was 15.34% and TOR was 15.12%. The segmental arteries of the unfractured vertebrae had a higher occlusion rate at thoracolumbar levels than at non-thoracolumbar levels. There was no significant difference between the IVC group and the non-IVC group in the fractured levels artery occlusion rate (20.24 ± 28.08 vs 9.78 ± 19.56, P = 0.156) or the total segmental arteries occlusion rate (13.83 ± 12.04 vs 11.57 ± 9.25, P = 0.476). Conclusions In patients with vertebral osteoporotic fracture, segmental artery occlusion is not associated with the development of intravertebral cleft.

Purpose The goal of this study was to evaluate the interrelationship between different magnetic resonance (MR) imaging measures and their validity in assessing the severity of acute traumatic spinal cord injury (tSCI) and predicting neurological outcomes. Methods We performed a preoperative multicenter cohort study of 89 patients with acute tSCI and preoperative MR imaging within 24 h after injury. We assessed several MR imaging measures of injury, including axial grade (Brain and Spinal Injury Center [BASIC] score), sagittal grade, length of injury, maximum canal compromise (MCC), and maximum spinal cord compression (MSCC). Principal component analysis (PCA) was applied to evaluate the interrelationship between different MR imaging measures. Spearman correlation and regression analyses were applied to assess injury severity and predict neurological impairment. The severity was assessed by the American Spinal Injury Association Impairment Scale (AIS) at admission, while neurological outcome was defined by AIS grade change at 6 weeks, AIS grade and SCIM score at 1 year after surgery. Results The PCA identified 2 clusters of MR imaging variables related to 1) measures of intrinsic cord signal abnormality (BASIC score, sagittal grade and length of injury) and 2) measures of extrinsic cord compression (MCC and MSCC). Neurological outcome and injury severity were best accounted for by MR imaging measures of intrinsic cord signal abnormalities, with the BASIC score representing the most accurate predictor of short-term and long-term neurological outcomes. Conclusion We determined the superior significance of the BASIC score in assessing injury severity, predicting early AIS improvement, AIS grade and SCIM score at 1 year compared with other MR imaging measures.

Objectives: XNW4107 is a novel beta-lactamase inhibitor that possesses broad activity against serine-beta-lactamases. XNW4107 in combination with imipenem exhibited potent in vitro activity against carbapenem-resistant bacteria and particularly against carbapenem-resistant Acinetobacter baumannii. This study aimed to evaluate the in vitro and in vivo antibacterial activities of imipenem/XNW4107. Methods: The minimum inhibitory concentrations, minimum bactericidal concentrations, time-kill curves, post-antibiotic effects, and spontaneous frequency of resistance were used to investigate the imipenem/XNW4107 in vitro activity. A mouse systemic infection model was used to evaluate the imipenem/XNW4107 in vivo efficacy. Results: MIC90 of imipenem/XNW4107 against imipenem-nonsusceptible A. baumannii (n = 106) was 8 mg/L, which was 16-fold lower than the MIC90 of imipenem; the resistance rate decreased from 90% to 20% applying the CLSI imipenem breakpoint. MIC90 of imipenem/XNW4107 against imipenem-resistant Klebsiella pneumoniae (n = 54) was 2 mg/L, which was 128-fold lower than the MIC90 of imipenem; 80% imipenem-nonsusceptible Pseudomonas aeruginosa (n = 101) exhibited MICs of imipenem/XNW4107 from 2 to 8 mg/L, which were 4- to 8-fold lower than the MICs of imipenem. Imipenem/XNW4107 was bactericidal against A. baumannii, K. pneumoniae, and Escherichia coli. The time-kill curves showed that increasing concentrations did not result in progressively increased killing at concentrations >4 x MIC. Imipenem/XNW4107 has a low potential for resistance development in tested strains except for K. pneumoniae. Imipenem/XNW4107 provided good protection against imipenem-resistant A. baumannii and K. pneumoniae in vivo. Conclusions: The broad-spectrum profile and potent in vitro and in vivo antibacterial activities support imipenem/XNW4107 as a promising investigational candidate. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Objective: Cefoperazone/sulbactam is a commonly used antibiotic combination against the extended-spectrum beta-lactamases (ESBLs)-producing bacteria. The objective of this study was to evaluate the efficacy of a new cefoperazone/sulbactam combination (3:1) for Enterobacteriaceae infection via model-informed drug development (MIDD) approaches. Methods: Sulperazon [cefoperazone/sulbactam (2:1)] was used as a control. Pharmacokinetic (PK) data was collected from a clinical phase I trial. Minimum inhibitory concentrations (MICs) were determined using two-fold broth microdilution method. The percent time that the free drug concentration exceeded the minimum inhibitory concentration (%fT>MIC) was used as the pharmacokinetic/pharmacodynamic indicator correlated with efficacy. Models were developed to characterize the PK profile of cefoperazone and sulbactam. Monte Carlo simulations were employed to determine the investigational regimens of cefoperazone/sulbactam (3:1) for the treatment of infections caused by Enterobacteriaceae based on the probability of target attainment (PTA) against the tested bacteria. Results: Two 2-compartment models were developed to describe the PK profiles of cefoperazone and sulbactam. Simulation results following the single-dose showed that the regimens of cefoperazone/sulbactam combinations in the ratios of 3:1 and 2:1 achieved similar PTA against the tested bacteria. Simulation results from the multiple-dose showed that the dosing regimen of cefoperazone/sulbactam (4 g, TID, 3 g:1 g) showed slightly better antibacterial effect than cefoperazone/sulbactam (6 g, BID, 4 g:2 g) against the Escherichia coli (ESBL−) and Klebsiella pneumoniae (ESBL−). For the other tested bacteria, the above regimens achieved a similar PTA. Conclusions: Cefoperazone/sulbactam (3:1) showed similar bactericidal activity to sulperazon [cefoperazone/sulbactam (2:1)] against the tested bacteria. For the ESBL-producing and cefoperazone-resistant E. coli and K. pneumoniae, Cefoperazone/sulbactam (3:1) did not exhibit advantage as anticipated. Our study indicated that further clinical trials should be carried out cautiously to avoid the potential risks of not achieving the expected target.

Purpose We designed a prospective cohort study based on magnetic resonance angiography (MRA) to identify whether the degree of Kummell disease (KD) vertebral artery occlusion is more severe than that of simple vertebral compression fractures. Methods We enrolled elderly patients with VCFs who met the established criteria from January 2019. MRA was used to determine the degree of vertebral artery occlusion. We defined the lesion segmental occlusion rate (LSOR) as the sum of the ischemic values of the bilateral vertebral segmental arteries (0 means expedite, 1 means stenosis, 2 means occlusion; range from 0–4). The average LSOR is the sum of LSORs divided by the number of vertebrae. Follow-up outcomes included VAS and ODI scores after surgery. X-rays were re-examined at 1 year after surgery to determine whether the vertebral body had recollapsed. Results 25 cases of KD segments and 37 cases of non-KD segments were included. The average LSOR in KD segments was significantly higher than that in non-KD segments (1.44 vs 0.32, P<0.01). The recollapse rate of the KD segments after one year was significantly higher than that in non-KD segments (56% vs 27%, P=0.03). In non-KD segments, 57.1% of segments with a high LSOR (1–2) recollapsed, and 20% of segments with a low LSOR (0) recollapsed (P=0.045) Conclusions The degree of artery occlusion in the KD segment is more serious than that in the non-KD segment. KD segments or non-KD segments with a high degree of artery occlusion will have a higher recollapse rate.

目的 研究应用骨水泥增强椎弓根钉固定治疗Kümmell病的有效性和安全性.方法 对2017年1月至2019年6月北京大学人民医院25例应用骨水泥增强椎弓根钉固定治疗Kümmell病患者进行回顾性研究,记录患者的手术时间、术中出血量、骨水泥体积.随访过程中通过腰椎正侧位X线片和CT进一步评价病椎高度、Cobb角;采用腰痛视觉模拟评分(VAS)评定临床症状改善情况,采用Oswestry功能障碍指数(ODI)评分评定术后功能改善情况.结果 VAS评分、ODI评分、病椎高度和后凸Cobb角度显示,术前和术后1周、术前和末次随访之间比较,差异有统计学意义(P＜0.05),术后1周和末次随访的随访值之间仅VAS评分比较差异无统计学意义(P＞0.05),而ODI评分、病椎前缘高度和Cobb角的差异具有统计学意义(P＜0.05).结论 骨水泥增强椎弓根钉内固定治疗Kümmell病可以减少脊柱后凸畸形、恢复椎体高度、缓解疼痛.尽管可能存在椎体高度丢失相关远期问题,但远期患者功能依旧恢复较好且并发症率较低,是一种安全有效的治疗方式.

The objective of this study is to establish an ankylosing spondylitis (AS) thoracolumbar fracture finite element (FE) model and provide a proper posterior fixation choice from the biomechanical perspective. The ankylosing spondylitis T9-L5 FE model was built and the range of motion (ROM) was compared to previous studies. The L1 transverse fracture was simulated and was separately fixed by five different patterns. The pull force and yielding force of the screws, the von Mises stress of the internal fixation, and the displacement of fracture site were analyzed to evaluate the proper fixation pattern for thoracolumbar fracture of AS. ROM of AS model was obviously restricted comparing to the normal vertebral experimental data. All the fixation patterns can stabilize the fracture. At least four levels of fixation can reduce the von Mises stress of the internal fixation. Four levels fixation has a higher pull force than the six levels fixation. Skipped level fixation did not reduce the stress, pull force and yielding force. The kyphosis correction did not change the biomechanical load. At least 4 levels fixation was needed for AS thoracolumbar fracture. The cemented screws should be chosen in 4 levels fixation to increase the holding of the screws. The skipped fixation has no advantage. The kyphosis correction can be chosen after weighing the pros and cons.

PKP手术是治疗骨质疏松性椎体压缩骨折( osteoporotic vertebral com-pression fracture,OVCF)的主流微创术式,镇痛迅速,畸形矫正效果较佳,但手术存在一定的骨水泥渗漏风险,尤其对于骨折椎周壁不完整者,其骨水泥渗漏率更高[1].为此,有学者提出双侧椎弓根入路穿刺定位,确保球囊扩张后双侧通道具备互通性,在压缩严重一侧灌注骨水泥,另一侧低压引导,以降低骨水泥的渗漏,保证双侧骨水泥良好分布,也被称为"压力引导式PKP术"[2].本研究现纳入 45 例周壁破损 OVCF 患者,均采用压力引导式PKP 术治疗,报道如下.

Background: Vancomycin-resistant Enterococcus (VRE), as an important nosocomial pathogens, can be carried in gut for a long period and its colonization status associated with the subsequent infections. The aim of this study was to investigate the frequency of intestinal VRE colonization and identify the risk factors associated with VRE carriage in intensive care patients. Methods: We conducted a 4-week cross-sectional study at six hospitals in Beijing, China. Patients admitted to Intensive Care Units (ICUs) were screened for intestinal colonization of VRE every Tuesday morning. Rectal swabs were selectively cultured for VRE, then the identified strains were analyzed by PCR to detect the glycopeptide resistance gene and were characterized by MLST. Risk factors were recorded to assess their effect on VRE acquisition during ICUs stay. Results: Of 148 patients recruited, 46 (31.1%) were colonized with VRE, with the majority (n=42) being Enterococcus faecium . In total, 78.3% of the VRE were vanA positive and 15.2% vanM positive, while 6.5% undetected glycopeptide resistance gene. The predominant ST was ST78 (47.6%) followed by ST192 (14.3%), ST555 (9.5%), ST789 (9.5%), ST547 (4.8%), and ST922 (4.8%). Risk factors associated with VRE carriage were age of >65 years, a longer length of ICU stay, use of an endotracheal tube, and prior glycopeptides use. Conclusions: The overall incidence proportion of VRE colonization at ICUs was relatively high in Beijing, and clonal expansion and horizontal transmission of resistant genes were both found here. Routine screening is necessary to prevent the dissemination of VRE.

Crustins are widely distributed among different crustacean groups. They are characterized by a whey acidic protein (WAP) domain, and most examined Crustins show activity against Gram-positive bacteria. This study reports two Crustins, Al-crus 3 and Al-crus 7, from hydrothermal vent shrimp, Alvinocaris longirostris. Al-crus 3 and Al-crus 7 belong to Crustin Type IIa, with a similarity of about 51% at amino acid level. Antibacterial assays showed that Al-crus 3 mainly displayed activity against Gram-positive bacteria with MIC50 values of 10–25 μM. However, Al-crus 7 not only displayed activity against Gram-positive bacteria but also against Gram-negative bacteria Imipenem-resistant Acinetobacter baumannii, in a sensitive manner. Notably, in the effective antibacterial spectrum, Methicillin-sensitive Staphylococcus aureus, Escherichia coli (ESBLs) and Imipenem-resistant A. baumannii were drug-resistant pathogens. Narrowing down the sequence to the WAP domain, Al-crusWAP 3 and Al-crusWAP 7 demonstrated antibacterial activities but were weak. Additionally, the effects on bacteria did not significantly change after they were maintained at room temperature for 48 h. This indicated that Al-crus 3 and Al-crus 7 were relatively stable and convenient for transportation. Altogether, this study reported two new Crustins with specific characteristics. In particular, Al-crus 7 inhibited Gram-negative imipenem-resistant A. baumannii.

Purpose To detect the relationship between the vertebral artery occlusion and the intravertebral cleft (IVC). Methods A prospective evaluation of the vertebral segmental artery condition from the T10 to L4 with the magnetic resonance angiography (MRA) was performed in 44 osteoporosis vertebral compression fracture (OVCF) patients. The artery condition was divided into the patency, narrow, occlusion. The lesion segmental occlusion rate (LSOR) and the total occlusion rate (TOR) was calculated. The relation of the vertebral artery occlusion and the IVC formation was assessed with the univariate analysis. Results LOSR was 15.34% and TOR was 15.2%. The segmental arteries of the unfractured vertebrae had higher occlusion rate in thoracolumbar levels than non-thoracolumbar levels. Neither lesion levels arteries occlusion nor the total segmental arteries occlusion was associated with the IVC. Conclusions Vertebral compression fracture did not lead to the segmental artery occlusion. The segmental artery occlusion more likely happened in the thoracolumbar levels. The segmental artery occlusion did not lead to the IVC.

Background Vertebral augmentation is the first-line treatment for the osteoporosis vertebral compression fractures. Bone cement leakage is the most common complication of this surgery. This study aims to assess the risk factors for different types of cement leakage and provides a nomogram for predicting the cement intradiscal leakage. Methods We retrospectively reviewed 268 patients who underwent vertebral augmentation procedure between January 2015 and March 2019. The cement leakage risk factors were evaluated by univariate analysis. Different types of cement leakage risk factors were identified by the stepwise logistic analysis. We provided a nomogram for predicting the cement intradiscal leakage and used the concordance index to assess the prediction ability. Results A total of 295 levels of vertebrae were included, with a leakage rate of 32.5%. Univariate analysis showed delayed surgery and lower vertebral compression ratio were the independent risk factors of cement leakage. The stepwise logistic analysis revealed percutaneous vertebroplasty was a risk factor in vein cement leakage; delayed surgery, preoperative compression ratio, and upper endplate disruption were in intradiscal cement leakage; age, preoperative fracture severity, and intravertebral vacuum cleft were in perivertebral soft tissue cement leakage; no factor was in spinal canal cement leakage. The nomogram for intradiscal cement leakage had a precise prediction ability with an original concordance index of 0.75. Conclusions Delayed surgery and more vertebral compression increase the risk of cement leakage. Different types of cement leakage have different risk factors. We provided a nomogram for precise predicting the intradiscal cement leakage.

STUDY DESIGN:Meta-analysis. OBJECTIVES:To provide up-to-date evidence-based outcomes for the incidence and risk factors of adjacent vertebral fracture (AVF) after the vertebral augmentation. METHODS:The MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies assessing the risk factors of adjacent vertebral fracture after vertebral augmentation until June 2020. The AVF incidence and factors potentially affecting AVF were extracted and pooled. RESULTS:A total of 16 studies, encompassing 2549 patients were included in the meta-analysis. The pooled incidence of AVF was 14% after vertebral augmentation. Female, lower T-score, thoracolumbar junction fracture, intravertebral cleft, more injected cement volume, intradiscal cement leakage significantly increased the risk of AVF. Age, body mass index, steroid medication, Cobb angle change, postoperative Cobb angle showed no significant association with AVF. CONCLUSIONS:Identifying the risk factors of AVF can facilitate prevention strategy to avoid the AVF. Female, T-score, thoracolumbar junction fracture, intravertebral cleft, more cement volume, and intradiscal cement leakage increased the risk of AVF.

Objective To evaluate in vitro antimicrobial effect of fosfomycin sodium single use and combination with other antimicrobial agents on clinically isolated Staphylococcus aureus (S.aureus), Klebsiella pneumoniae (K.pneumoniae) and Pseudomonas aeruginosa (P.aeruginosa) in China.Methods Combined antimicrobial susceptibility testing was performed with checkerboard method, minimal inhibitory concentrations (MICs) were detected by two-fold agar dilution method, susceptibility of S.aureus (n=113 strains), K.pneumoniae (n=108 strains), and P.aeruginosa (n=110 strains) isolated from 18 hospitals in China in recent three years was determined by single and combined antimicrobial susceptibility testing.Results MIC50 value of fosfomycin sodium single use were all≤32 mg/L against all tested strains, regardless of whether strains were resistant to other antimicrobial agents or not.The synergistic rate of fosfomycin sodium with levofloxacin, minocycline, oxacillin, and clindamycin against methicillin-resistant S.aureus (MRSA) was＞43％.Synergistic rate of fosfomycin sodium with levofloxacin and imipenem against imipenem-nonsusceptible P.aeruginosa was＞35％, synergistic rates of fosfomycin sodium with tested antimicrobial agents against imipenem-susceptible P.aeruginosa were all＞35％.Conclusion Fosfomycin sodium still has good antimicrobial activity against common clinical drug-resistant bacteria, such as MRSA, extended-spectrumβ-lactamase-producing K.pneumoniae and so on, it has synergistic effect with many other kinds of antimicrobial agents, suggesting that in the limited treatment of infection caused by drug-resistant bacteria, fosfomycin in combination with other antimicrobial agents may be a useful choice.