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Currently, little is known about the prognostic value of tumor growth rate (TGR) in spinal giant cell tumors of bone (GCTB).To investigate the correlation of TGR with clinicopathological features, immune microenvironment, prognosis, and response to denosumab treatment of spinal GCTB.A total of 128 patients with spinal GCTB treated at 5 centers from 2011 to 2021 were included. TGR was assessed by 2 independent neuroradiologists using at least 2 preoperative thin-section magnetic resonance imaging scans at a minimum interval of 2 months. Immunohistochemistry was used to assess tumor-infiltrating lymphocyte subtypes for CD3, CD4, CD8, CD20, PD-1, PD-L1, and Foxp3. Then, these parameters were analyzed for their associations with patient outcomes (progression-free survival and overall survival), clinicopathological features, and denosumab treatment responsiveness.High TGR predicted both poor progression-free survival and overall survival (both P.001). In addition, TGR was associated with postoperative neurological dysfunction (P.001), Enneking staging (P = .016), denosumab treatment responsiveness (P = .035), and the number of CD3+ (P.001), PD-1+ (P = .009), PD-L1+ (P.001), and FoxP3+ tumor-infiltrating lymphocyte (P = .02). Importantly, TGR outperformed the traditional Enneking, Campanacci, and American Joint Committee on Cancer staging systems in predicting the clinical outcomes of spinal GCTB.These data support the use of TGR as a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy of spinal GCTB, which may be helpful in guiding prognostic risk stratification and therapeutic optimization of patients.

The aim of this study was to investigate the clinical features, distribution and antimicrobial susceptibility of Nocardia species isolated from pulmonary nocardiosis cases in tertiary hospital in China. The species were collected from January 1, 2018 to May 31, 2019 and identified using MALDI-TOF MS or PCR. Antimicrobial susceptibility testing was performed using the broth microdilution method. Within the 44 Nocardia species, N. farcinica was the most frequently identified species (n = 36), followed by N. nova (n = 5), N. otitidiscaviarum (n = 1), N. cyriacigeorgica (n = 1), and N. transvalensis (n = 1). The top three predisposing factors of pulmonary nocardiosis were chronic obstructive pulmonary disease (45.5%), hypertension (34.1%), and tuberculosis (31.8%). All 44 Nocardia strains were susceptible to amikacin, trimethoprim / sulfamethoxazole, and linezolid. The resistance rates of Nocardia to amoxicillin-clavulanic acid, ciprofloxacin, clarithromycin, ceftriaxone, tobramycin, and imipenem were 4.5%, 9.1%, 79.5%, 72.7%, 63.6%, and 38.6%, respectively. Two Nocardia strains had decreased sensitivity to trimethoprim / sulfamethoxazole. In conclusion, N. farcinica was the most frequently isolated Nocardia species in the First Hospital of Changsha. All isolated clinical Nocardia strains showed susceptible to amikacin, trimethoprim / sulfamethoxazole, and linezolid, suggesting that these drugs can be primary therapeutic choices for treating Nocardia infections.

To investigate the relationship of biofilm-forming ability of (PA) with swimming motility, twitching motility and virulence gene distribution. A total of 192 clinical isolates of PA were collected consecutively. Microtiter plate method was used to evaluate the ability to form biofilm. The swimming and twitching motilities were detected by plate method. Polymerase chain reaction (PCR) was used to detect virulence genes. Of the 192 PA clinical isolates, 186 (96.9%) showed biofilm-forming ability. Among them, 36 isolates showed weak biofilm-forming ability, 84 exhibited moderate biofilm-forming ability and 66 showed strong biofilm-forming ability. The diameters of the swimming ring for PA with none biofilm-forming ability, weak biofilm-forming ability, moderate biofilm-forming ability, strong biofilm-forming ability were (9.12±6.76), (18.42±7.51), (19.10±4.77) and respectively. The diameters of the twitching ring for PA in above groups were (8.38±1.50), (17.21±7.42), (18.49±5.62) and respectively. The swimming motility and twitching motility of none biofilm-forming ability group were weaker than biofilm-forming ability groups (all

Study Design: Retrospective pooled analysis of individual patient data. Objectives: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. Methods: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. Results: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. Conclusion: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

Background Currently, the measurement of immune cells in previous studies is usually subjective, and no immune-based prognostic model has been established for chordoma. In this study, we sought to simultaneously measure tumor-infiltrating lymphocyte (TIL) subtypes in chordoma samples using an objective method and develop an immune risk score (IRS) model for survival prediction. Methods Multiplexed quantitative immunofluorescence staining was used to determine the TIL levels in the tumoral and stromal subareas of 114 spinal chordoma specimens (54 in the training and 60 in the validation cohort) for programmed death-1 (PD-1), CD3, CD8, CD20 (where CD is cluster of differentiation), and FOXP3. Flow cytometry was performed to validate the immunofluorescence assay for lymphocyte measurement on an additional five fresh chordoma specimens. Subsequently, the IRS model was built using the least absolute shrinkage and selection operator (LASSO) Cox regression method. Results Flow cytometry and quantitative immunofluorescence showed similar lymphocytic percentages and TIL subpopulation proportions in the fresh tumor specimens. With the training data, the LASSO model identified four immune features for IRS construction: tumoral FOXP3, tumoral PD-1, stromal FOXP3, and stromal CD8. In both cohorts, a high IRS was significantly associated with tumoral programmed cell death-1 ligand 1 expression, Enneking inappropriate tumor resection, and surrounding muscle invasion by tumor. Multivariate Cox regression and stratified analysis in the two cohorts revealed that the IRS was an independent predictor and could effectively separate patients with similar Enneking staging into different risk subgroups, with significantly different survival rates. Further receiver operating characteristic analysis found that the IRS classifier had a better prognostic value than the traditional clinicopathological factors and compensated for the deficiency of Enneking staging for outcome prediction. More importantly, a nomogram based on the IRS and clinical predictors showed adequate performance in estimating disease recurrence and survival of patients. Conclusions These data support the use of the IRS signature as a reliable prognostic tool in spinal chordoma and may facilitate individualized therapy decision making for patients.

Purpose Outbreaks of infection due to carbapenem-resistant Enterobacterales (CRE), including New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli, have been increasingly reported worldwide, primarily in adults and rarely in children. The goal of this study was to characterize an outbreak of infection caused by NDM-5-producing E. coli in a children's hospital in China. Methods A total of 86 CRE isolates were collected from 85 hospitalized children between June 2017 and May 2018. These isolates were subjected to multiple phenotypic and molecular tests, including in vitro antimicrobial susceptibility testing, PCR, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and whole-genome sequencing (WGS). Results Among the 86 CRE isolates, we identified 9 NDM-5-producing E. coli isolates, with 5 of them sharing the same PFGE pattern, same MLST type (ST410), same plasmid replicon type (IncFII), and nearly the same set of additional resistance genes. All 9 isolates were resistant to most antimicrobial agents, including carbapenems, cephalosporins, and levofloxacin, while being sensitive to trimethoprim/sulfamethoxazole, amikacin, tigecycline, and colistin. According to the clinical background, all 9 isolates were collected in a period of < 3 months from infants among whom there was overlap in the time of hospitalization. None of them had a travel history. Conclusion Our analysis suggests an outbreak of clonal dissemination, presumably due to nosocomial transmission. This study represents the first documented outbreak of NDM-5-producing E. coli mediated by IncFII in infants. Close monitoring is urgently needed to prevent and control the spread of this difficult-to-treat superbug.

Background: The clinical characteristics and prognostic factors of axial chondroblastoma (ACB) are still poorly understood.Purpose: To characterize clinicopathological characteristics in a large ACB cohort and investigate their correlation with survival. We also sought to compare these results with extra-axial CB (EACB).Methods: Our institution's local database was retrospectively reviewed and included a total of 132 CB patients, including 61 ACB patients and 71 EACB patients. Immunohistochemistry was used to assess the expression levels of Vimentin (Vim), S100, and cytokeratin (CK) on tumor cells in 132 tissue specimens.Results: Overall, ACB and EACB had similar characteristics, except for older age and tumor size, as well as higher Vim expression, incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction. Whereas wide resection and absence of invasion of surrounding tissues were consistently associated with favorable survival in the ACB and EACB cohorts in univariate analysis, most parameters showed differential prognostic significance between the 2 groups. Significant prognostic factors for local recurrence-free survival in multivariate analysis included the type of resection and chicken-wire calcification in the ACB cohort. Multivariate analysis of overall survival demonstrated that the type of resection was a significant predictor in the ACB cohort, whereas the type of resection and postoperative sensory or motor dysfunction were predictive of overall survival in the EACB group.Conclusion: These data suggest that there may be distinct biological behaviors between ACB and EACB and may provide useful information to better understand the prognostic characteristics of patients with ACB and to improve outcome prediction in patients with ACB.

Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD. Abbreviations : IDD; intervertebral disc degeneration ncRNAs; non-coding RNAs lncRNAs; long non-coding RNAs miRNAs; microRNAs NP; nucleus pulposus qRT-PCR; quantitative reverse transcription–PCR LBP; Low back pain ORF; open reading frame HOTAIR; Hox transcript antisense intergenic RNA FAF1; Fas-associated protein factor-1 Erk; extracellular signal-regulated kinase TUG1; Taurine Up-regulated Gene 1 HIF1A hypoxia-inducible factor 1-alpha PI3K; phosphoinositide-3 kinase AIS; adolescent idiopathic scoliosis ECM; extracellular matrix LN;lupus nephritis CT;computed tomography MRI; magnetic resonance imaging PBS; phosphate-buffered salin PBS; phosphate-buffered salin PVDF; polyvinylidene fluoride TBST; Tris-buffered saline Tween ECL; enhanced chemiluminescence RIP; RNA immunoprecipitation

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Background Small colony variants (SCVs) of Staphylococcus aureus (S. aureus) frequently lead to chronic and recurrent infections, but they are always ignored and there are few researches on their clinical isolates. We intended to investigate the prevalence and characteristics of S. aureus SCVs. Methods None‐duplicated S. aureus strains isolated from wound samples were collected from January 2018 to December 2020. The characteristics (i.e. colony morphology, growth rate, coagulase, biofilm formation, and pathogenic characteristics), antimicrobial susceptibilities, and resistance mechanisms of SCVs were also investigated. The genetic background of SCVs was analyzed through staphylococcal protein A (SPA) typing, sequence typing, and pulse field gel electrophoresis (PFGE). Results Three SCVs were screened from 278 S. aureus strains (1.1%). They formed pinpoint white colonies on blood agar plates with weak hemolysis. The reproduction speed in liquid medium was very slow for SCVs strains. The coagulase weakened or disappeared, and the ability to form biofilm varied greatly. Only slight inflammation was triggered when wound infected. The SPA typing was t2592, t233, and t023, and the sequence typing was ST88, ST239, and ST965, respectively. The PFGE revealed three SCVs were singletons. Conclusions The rate of SCVs in wound sample is low in our hospital, and the formation is associated with the usage of antimicrobial. SCVs grow slowly, and their colony morphology and biochemical characteristics are significantly different from classic S. aureus. SCVs may cause chronic infection and weak inflammation. SCVs form in resistant or susceptible strains, and there is no clonal epidemic in this hospital., Through investigating the epidemiology and characteristics of small colony variants (SCVs) of S. aureus in wound specimens, here we found that the formation of SCVs is very rare and closely related to the usage of antibiotics. At the same time, the formation of SCVs may not be limited to specific resistance types and genetic types. Therefore, clinical laboratories should pay more attention to SCVs to facilitate effective treatment of SCVs infection.

Background: The growing rod (GR) technique is a viable alternative for the current non-fusion treatment of early-onset scoliosis (EOS). However, conventional GRs are lengthened to allow for spinal growth, which requires multiple surgeries under general anesthesia in association with high cost and potentially negative psychosocial outcomes. Methods: In this study, growing rods with a sliding pedicle screw system (GRSPSS) was developed for the treatment of EOS without need of repeated operative lengthening. A retrospective review of clinical data on EOS patients who were treated with GRSPSS system was performed to evaluate the safety and efficacy of this technique. Results: 33 patients received GRSPSS instrumentation and 18 of them were finally included with more than 5-year follow-up data. There were 10 girls and 8 boys with a mean age of 9 years old. The mean preoperative curve (56.6 degrees) was corrected to 15.5 degrees at the 4-week follow-up. This magnitude of correction maintained at the 5-year follow-up. T1-S1 spinal height gained an average of 42 mm on measurement from postoperative to the final follow-up period. Complications included transient neurological deficit in one case and skin infection at one end of the rods in three cases during the early-postoperative period. Two patients required minimally invasive revision surgery because of shoulder imbalance. Rod breakage occurred in two cases.Conclusions: The GRSPSS can safely and effectively correct spinal deformity at a 5-year follow-up. This new instrumentation may be a promising approach for facilitating spinal growth without repeated lengthening operations.

BackgroundCurrently, the clinicopathological and prognostic characteristics of dedifferentiated chordoma (DC) and poorly differentiated chordoma (PDC) remain poorly understood. In this study, we sought to characterize clinicopathological parameters in a large PDC/DC cohort and determine their correlations with progression-free survival (PFS) and overall survival (OS) of patients. We also attempted to compare clinical features between PDC/DC and conventional chordoma (CC).MethodsLiterature searches (from inception to June 01, 2020) using Medline, Embase, Google Scholar and Wanfang databases were conducted to identify eligible studies according to predefined criteria. The local database at our center was also retrospectively reviewed to include CC patients for comparative analysis.ResultsFifty-eight studies from the literature and 90 CC patients from our local institute were identified; in total, 54 PDC patients and 96 DC patients were analyzed. Overall, PDC or DC had distinct characteristics from CC, while PDC and DC shared similar clinical features. Adjuvant radiotherapy and chemotherapy were associated with both PFS and OS in PDC patients in the univariate and/or multivariate analyses. In the DC cohort, tumor resection type, adjuvant chemotherapy and tumor dedifferentiation components significantly affected PFS, whereas none of them were predictive of outcome in the multivariate analysis. By analyzing OS, we found that surgery, resection type and the time to dedifferentiation predicted the survival of DC patients; however, only surgery remained significant after adjusting for other covariables.ConclusionsThese data may offer useful information to better understand the clinical characteristics of PDC/DC and may be helpful in improving the outcome prediction of patients.

Long noncoding RNAs (lncRNAs) and miRNAs have been reported to participate in intervertebral disc degeneration (IDD) progression. However, the key lncRNA-miRNA axis and its corresponding affected hub genes in IDD remain unknown. In this study, weighted gene coexpression network analysis (WGCNA) was first used to determine the key gene cluster and hub genes implicated in IDD progression. The expression levels of ADIRF-AS1, miR-214-3p, and SERPINA1 in nucleus pulposus (NP) tissues were detected. The ADIRF-AS1/miR-214-3p/SERPINA1 axis was identified, and its effects on the proliferation, senescence, and apoptosis of NP cells were investigated in vitro and in vivo. SERPINA1 overexpression in NP cells promoted cell viability and inhibited cell apoptosis and senescence. Moreover, SERPINA1 regulated the IDD grade in rat models. The lncRNA ADIRF-AS1 was downregulated in high-grade degeneration NP tissues and positively correlated with SERPINA1. ADIRF-AS1 overexpression attenuated cellular degenerative changes in NP cells. miR-214-3p directly bound to SERPINA1 and ADIRF-AS1 and negatively regulated ADIRF-AS1 expression. miR-214-3p inhibition exerted similar effects on cellular degenerative changes in NP cells to SERPINA1 or ADIRF-AS1 overexpression. Furthermore, miR-214-3p overexpression partially reversed the effects of ADIRF-AS1 overexpression. Collectively, these data suggest that ADIRF-AS1 overexpression could mitigate IDD by binding to miR-214-3p to upregulate SERPINA1. Additional studies (especially those using an axial loading-induced IDD animal model) will be needed to further validate the role of the ADIRF-AS1/miR-214-3p/SERPINA1 signaling axis in IDD progression.

This study aimed to investigate the clinical features, distribution, and antimicrobial susceptibility of Nocardia species isolated from pulmonary nocardiosis cases in a tertiary hospital in China. The species were collected from January 1, 2018, to May 31, 2019, and identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry or polymerase chain reaction. Antimicrobial susceptibility testing was performed using the broth microdilution method. Within the 44 Nocardia species, N. farcinica was the most frequently identified species (n = 36), followed by N. nova (n = 5), N. otitidiscaviarum (n = 1), N. cyriacigeorgica (n = 1), and N. transvalensis (n = 1). The top 3 predisposing factors of pulmonary nocardiosis were chronic obstructive pulmonary disease (45.5%), hypertension (34.1%), and tuberculosis (31.8%). All 44 Nocardia species were susceptible to amikacin, trimethoprim/sulfamethoxazole, and linezolid. The resistance rates of Nocardia to amoxicillin-clavulanic acid, ciprofloxacin, clarithromycin, ceftriaxone, tobramycin, and imipenem were 4.5%, 9.1%, 79.5%, 72.7%, 63.6%, and 38.6%, respectively. Two Nocardia strains had decreased sensitivity to trimethoprim/sulfamethoxazole. In conclusion, N. farcinica was the most frequently isolated Nocardia species in the First Hospital of Changsha. All the isolated clinical Nocardia species showed susceptibility to amikacin, trimethoprim/sulfamethoxazole, and linezolid, suggesting that these drugs can be primary therapeutic choices for treating Nocardia infections.

Introduction: Carbapenem-resistant Klebsiella pneumoniae (KP) serves as a major threat to onco-hematological patients, resulting in great morbidity and mortality. The purpose of our study was to identify the risk factors for KP bloodstream infections (BSIs) and mortality in onco-hematological patients. Methodology: A retrospective observation study was conducted on KP BSIs in the onco-hematology departments at Xiangya hospital from January 2014 to September 2018. Multivariate analysis was employed to identify the independent risk factors for carbapenem-resistant (CR) KP BSIs and related mortality. Results: A total of 89 strains of KP were analyzed in our study, in which 20 strains were CRKP. The only risk factor for CRKP BSI was carbapenem exposure within 30 days before the onset of BSIs (HR 25.122). The 30-day mortality was 24.7%. CRKP caused more mortality than carbapenem-susceptible KP (55.0% vs 15.9%, P = 0.001). In the multivariate analysis, unresolved neutropenia (HR 16.900), diarrhea (HR 3.647) and RDW > 14% (HR 6.292) were independent risk factors for mortality, and appropriate empirical therapy (HR 0.164) was protective against mortality. Conclusions: Our findings showed that carbapenem resistance was spreading in our setting, and a precise combination of antibiotics covering the common pathogen is crucial to improving patient survival.

Introduction: The aim of our study was to evaluate the epidemiology, clinical features and risk factors for shock and mortality from Escherichia coli bacteremia among children and adolescents with hematological disorders. Methodology: A retrospective observational study of E. coli bacteremia in the hematology department at Xiangya Hospital from January 2013 to June 2018 was conducted. Clinical characteristics, laboratory results and antimicrobial susceptibility were analysed. Risk factors for shock and mortality were also investigated. Results: Of the 45 strains of E. coli, 73.3% were multidrug-resistant (MDR). Septic shock was observed in 51.1% of patients, and the 30-day all-cause mortality was 22.2%. The risk factors associated with shock were an elevated red blood cell distribution (RDW) value when bloodstream infections (BSIs) occurred (> 15%, OR, 6.840; 95% CI, 1.571 – 29.788) and a lower WBC count (< 300/mm3, OR, 6.761; 95% CI, 1.383 – 33.044). Multivariate analysis showed that only an elevated D-dimer level (> 0.5 mg/L, OR 12.250, 95% CI 1.268 – 118.361) was a risk factor for 30-day mortality. Furthermore, we observed decreases for RDW changes at two time points (neutropenia and BSIs occurred) in the non-shock group and survival group. Conclusions: MDR infections from E. coli bacteremia were common in pediatric hematological patients. In our setting, the laboratory results may serve as a clue for physicians to distinguish patients at higher risk for shock and mortality. Furthermore, RDW could be used as a biomarker to elucidate potential disorders in hematological patients.

Background Currently, clinical characteristics and prognostic factors of extra-axial chordoma (EAC) remain poorly understood. Objective To characterize clinicopathological characteristics in a large EAC cohort and investigate their correlation with survival. We also attempted to compare these outcomes with axial chordoma (AC). Methods Medline and Embase searches (from inception to February 28, 2018) were conducted to identify eligible studies as per predefined criteria. The local database at our center was also retrospectively reviewed to include additional patients. Results Forty-three studies from the literature and 86 patients from our local institute were identified, resulting in a total of 86 EAC patients and 75 AC patients for analysis. Overall, EAC had similar characteristics to AC, except for having higher CAM5.2 expression, common lobular growth pattern, and better prognosis. Whereas wide surgical resection was consistently associated with favorable survival in both EAC and AC cohorts on univariate analyses, most parameters showed differential prognostic implications between the 2 groups. Significant prognostic factors for local recurrence-free survival on multivariate analysis included type of surgery in both cohorts and tumor Brachyury expression and adjuvant radiotherapy in AC cohort. Multivariate analysis of overall survival demonstrated that type of surgery, tumor Brachyury expression, and duration of symptoms were significant predictors in the AC cohort, whereas none of the analyzed parameters were predictive of overall survival for the EAC group. Conclusion These data suggest potentially distinct biological behaviors between EAC and AC and may provide useful information to better understand the prognostic characteristics and improve the outcome prediction of EAC patients.

Background Fosfomycin has been proven to be a vital choice to treat infection caused by multidrug resistance bacteria, especially carbapenem-resistant Klebsiella pneumoniae (CRKP). However, fosfomycin resistant cases has been reported gradually. In this study, we reported the fosfomycin-resistant rate in CRKP strains and further revealed the molecular mechanisms in resistance gene dissemination. Results A total of 294 non-duplicated CRKP strains were collected. And 55 fosfomyin-resistant strains were detected, 94.5% of which were clustered to sequence type (ST) 11 by PCR followed up sequencing. PFGE further revealed two major groups and four singletons. The positive rates of genes responsible to fosfomycin and carbapenem resistance were 81.8% (fosA3), 12.7% (fosA5) and 94.5% (blaKPC-2), respectively. Genomic analysis confirmed insertion sequence (IS) 26 was the predominant structure surrounding fosA3. The fosA3 genes in six isolates were located on plasmids which were able to transfer to E. coli J53 recipient cells by means of conjugation. Conclusions Although the resistant rate of CRKP to fosfomycin is relatively low in our area, considering its gene is located on transferrable plasmid and inserted in IS structure, continuous monitoring is still needed.

Pseudomonas aeruginosa is noted for its intrinsic antibiotic resistance and capacity of acquiring additional resistance genes. In this study, the genomes of nine clinical P. aeruginosa isolates were fully sequenced. An extensive genetic comparison was applied to 18 P. aeruginosa accessory genetic elements (AGEs; 13 of them were sequenced in this study and located within P. aeruginosa chromosomes) that were divided into four groups: five related integrative and conjugative elements (ICEs), four related integrative and mobilizable elements (IMEs), five related unit transposons, and two related IMEs and their two derivatives. At least 45 resistance genes, involved in resistance to 10 different categories of antibiotics and heavy metals, were identified from these 18 AGEs. A total of 10 β-lactamase genes were identified from 10 AGEs sequenced herein, and nine of them were captured within class 1 integrons, which were further integrated into ICEs and IMEs with intercellular mobility, and also unit transposons with intracellular mobility. Through this study, we identified for the first time 20 novel MGEs, including four ICEs Tn6584, Tn6585, Tn6586, and Tn6587; three IMEs Tn6853, Tn6854, and Tn6878; five unit transposons Tn6846, Tn6847, Tn6848, Tn6849, and Tn6883; and eight integrons In1795, In1778, In1820, In1784, In1775, In1774, In1789, and In1799. This was also the first report of two resistance gene variants blaCARB-53 and catB3s, and a novel ST3405 isolate of P. aeruginosa. The data presented here denoted that complex transposition and homologous recombination promoted the assembly and integration of AGEs with mosaic structures into P. aeruginosa chromosomes.

Bo-Wen Zheng,1,2 Min-Liang Yang,2 Wei Huang,3 Bo-Yv Zheng,4 Tao-Lan Zhang,5 Jing Li,2 Guo-Hua Lv,2 Yi-Guo Yan,1,* Ming-Xiang Zou1,* 1Department of Spine Surgery, The First Affiliated Hospital, University of South China, Hengyang, 421001, People’s Republic of China; 2Department of Spine Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 3Health and Management Centre, The First Affiliated Hospital, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Orthopedics Surgery, General Hospital of the Central Theater Command, Wuhan, 430061, People’s Republic of China; 5Department of Radiation Oncology, Indiana University School of Medicine, IU Simon Comprehensive Cancer Center, Indianapolis, IN, 46202, USA*These authors contributed equally to this workCorrespondence: Ming-Xiang ZouDepartment of Spine Surgery, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang, Hunan, 421001, People’s Republic of ChinaTel +86 73485295624Fax +86 73482654334Email zouwei8887@126.comYi-Guo YanDepartment of Spine Surgery, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang, Hunan, 421001, People’s Republic of China, +86 73485295624, +86 73482654334Email yan_yiguo@qq.comObjective: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients.Methods: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features.Results: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan–Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance.Conclusion: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.Keywords: chondroblastoma, tumor-associated macrophages, tumor immune microenvironment, prognostic factors, survival analysis

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from the Surveillance Epidemiology and End Results database, with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general U.S. population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563,298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among the competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during the study period. While age, surgery, other/unknown race and tumors located at the transverse colon positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, a more recent year (2001–2015) of diagnosis, a grade II or III CRC, rectal cancer, or multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM that may be helpful for risk stratification and the therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Percutaneous endoscopic lumbar discectomy (PELD) has been widely used, before which foraminoplasty is necessary to widen the foramen for subsequent procedures. However, the learning curve of this technology is high, as the use of traditional reamers requires repeated intraoperative fluoroscopy. We sought to compare the clinical outcomes by using the visualized and traditional reamers in PELD foraminoplasty for the treatment of lumbar disc herniation.Eighty patients with lumbar disc herniation who were treated with PELD between 1 January 2017 and 1 January 2019 were retrospectively reviewed. The patients were randomly divided into 2 groups (40 patients in the Visualized Bone Reamer group) and (40 patients in the Traditional Bone Reamer group). Intraoperative fluoroscopy time, cannulation introduction time, visual analog scale, and Macnab criteria score were compared between the 2 groups.The mean follow-up durations were 17.41 ± 1.47 and 18.37 ± 1.69 months in the visualized and traditional groups, respectively. The average cannulation introduction time and intraoperative fluoroscopy times in the visualized group is significantly lower than those in traditional group (29.20 ± 3.31 vs. 39.85 ± 3.98 minutes, P0.001; and 12.30 ± 2.38 vs. 20.65 ±3.51 seconds, P0.001, respectively). One patient in the traditional group required reoperation, and no complications occurred in the visualized group. There were no severe durotomies or vascular or visceral injuries.Full-endoscopic foraminoplasty using a visualized reamer is safe and effective and can decrease intraoperative fluoroscopy time in PELD.

We recently read with great interest the article by Koo et al .1 In this retrospective study, the authors evaluated the effect of tumour necrosis factor (TNF) inhibitors on radiographic progression in patients with ankylosing spondylitis (AS) using real-world patient data with long-term follow-up information. They found that the TNF inhibitors could significantly impede the radiographic progression of AS patients. We commend the authors for performing this important study as the results could be very helpful in guiding practice in clinics. However, we noticed that the authors did not clarify the influence of TNF inhibitors on osteoporosis or vertebral fracture risk on imagings in the patients. Osteoporosis is a commonly recognised problem in AS population, which can lead to serious consequences for the patients. For instance, patients with AS may have severe fractures and resulting neurological dysfunctions even after minor trauma due to osteoporosis. Similarly, AS patients may be vulnerable to …

Background To evaluate clinical features, bacterial characteristics, and risk factors for shock and mortality of immunocompromised patients with Escherichia coli bacteremia. Methods A nearly 6‐year retrospective study of E coli bacteremia in 188 immunocompromised patients at Xiangya Hospital was conducted. Demographic, clinical, and laboratory data were documented. Phylogenetic background and virulence factors of E coli isolates were detected by polymerase chain reaction. Risk factors for shock and mortality were also investigated. Results Of all 188 E coli isolates, most prevalent virulence factors were fimH (91.0%), followed by traT (68.6%) and iutA (67.0%), while papG allele I, gafD, and cdtB were not detected. Phylogenetic group D was dominant (42.0%) among all isolates, and group B2 accounted for 17.6%, while group A and B1 accounted for 28.2% and 12.2%, respectively. In univariate analysis, ibeA and cnf1 were associated with mortality, which were not found in multivariate regression analysis. 22.3% of patients suffered shock, and 30‐day mortality rate was 21.3%. MDR (HR 2.956; 95% CI, 1.091‐8.012) was the only risk factor for shock, while adult (HR 0.239; 95% CI, 0.108‐0.527) was a protective factor. Multivariate analysis revealed that shock (HR 4.268; 95% CI, 2.208‐8.248; P 2 (HR 2.073; 95% CI, 1.087‐3.952; P = .027) were associated with fatal outcome. Conclusions Escherichia coli bacteremia was highly lethal in immunocompromised patients, and host‐related factors played major roles in poor prognosis, while bacterial determinants had little effect on outcome. This study also provided additional information about the virulence and phylogenetic group characteristics of E coli bacteremia.

Background Previous studies have suggested that interleukin (IL)-17A is a key factor that contributes to intervertebral disc degeneration (IDD), whereas autophagy has been shown to be a protective mechanism in IDD. However, the relationship between IL-17A and autophagy in IDD remains to be fully elucidated. This study sought to evaluate the association between IL-17 and autophagy and the potential mechanism through which IL-17A affects autophagy in IDD. Methods Intervertebral disc specimens were collected from 10 patients with lumbar disc herniation. Human degenerated nucleus pulposus (NP) cells were cultured in the presence or absence of IL-17A treatment. Western blot and monodansylcadaverine staining were used to measure autophagy levels in human degenerated NP cells. Subsequently, phosphatidylinositol 3-kinase (PI3K)/Akt/Bcl-2 pathway inhibitors were used to reveal the potential mechanism. Results IL-17A treatment inhibited the autophagic activity in human NP cells in a time- and dose-dependent manner. Moreover, monodansylcadaverine staining showed that cells treated with IL-17A had significantly fewer changes in their autophagic vacuoles compared with control-treated cells. After IL-17A treatment, expression levels of PI3K, p-Akt, and Bcl-2 in NP cells were significantly increased. Further assays with PI3K/Akt/Bcl-2 inhibitors revealed that IL-17A suppressed autophagy in NP cells by activating the PI3K/Akt/Bcl-2 signaling pathway. Conclusions These data suggest that IL-17A promotes IDD by inhibiting autophagy through activation of the PI3K/Akt/Bcl-2 signaling pathway and may offer new insights for targeted therapy of this disease.

Purpose Outbreaks of infection due to carbapenem-resistant Enterobacterales (CRE), including New Delhi metallo-β-lactamase (NDM)-producing Escherichia coli, have been increasingly reported worldwide, primarily in adults and rarely in children. The goal of this study was to characterize an outbreak of infection caused by NDM-5-producing E. coli in a children’s hospital in China. Methods A total of 86 CRE isolates were collected from 85 hospitalized children between June 2017 and May 2018. These isolates were subjected to multiple phenotypic and molecular tests, including in vitro antimicrobial susceptibility testing, PCR, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and whole-genome sequencing (WGS). Results Among the 86 CRE isolates, we identified 9 NDM-5-producing E. coli isolates, with 5 of them sharing the same PFGE pattern, same MLST type (ST410), same plasmid replicon type (IncFII), and nearly the same set of additional resistance genes. All 9 isolates were resistant to most antimicrobial agents, including carbapenems, cephalosporins, and levofloxacin, while being sensitive to trimethoprim/sulfamethoxazole, amikacin, tigecycline, and colistin. According to the clinical background, all 9 isolates were collected in a period of < 3 months from infants among whom there was overlap in the time of hospitalization. None of them had a travel history. Conclusion Our analysis suggests an outbreak of clonal dissemination, presumably due to nosocomial transmission. This study represents the first documented outbreak of NDM-5-producing E. coli mediated by IncFII in infants. Close monitoring is urgently needed to prevent and control the spread of this difficult-to-treat superbug.