Identification of pathogen composition in a Chinese population with iatrogenic and native vertebral osteomyelitis by using mNGS.

BACKGROUND: Early antimicrobial therapy is crucial regarding the prognosis of vertebral osteomyelitis, but early pathogen diagnosis remains challenging. OBJECTIVE: In this study, we aimed to differentiate the types of pathogens in iatrogenic vertebral osteomyelitis (IVO) and native vertebral osteomyelitis (NVO) to guide early antibiotic treatment. METHODS: A total of 145 patients, who had confirmed spinal infection and underwent metagenomic next-generation sequencing (mNGS) testing, were included, with 114 in the NVO group and 31 in the IVO group. Using mNGS, we detected and classified 53 pathogens in the 31 patients in the IVO group and 169 pathogens in the 114 patients in the NVO group. To further distinguish IVO from NVO, we employed machine learning algorithms to select serum biomarkers and developed a nomogram model. RESULTS: The results revealed that the proportion of the Actinobacteria phylum in the NVO group was approximately 28.40%, which was significantly higher than the 15.09% in the IVO group. Conversely, the proportion of the Firmicutes phylum (39.62%) in the IVO group was markedly increased compared to the 21.30% in the NVO group. Further genus-level classification demonstrated that Staphylococcus was the most common pathogen in the IVO group, whereas Mycobacterium was predominant in the NVO group. Through LASSO regression and random forest algorithms, we identified 5 serum biomarkers including percentage of basophils (BASO%), percentage of monocytes (Mono%), platelet volume (PCT), globulin (G), activated partial thromboplastin time (APTT) for distinguishing IVO from NVO. Based on these biomarkers, we established a nomogram model capable of accurately discriminating between the two conditions. CONCLUSION: The results of this study hold promise in providing valuable guidance to clinical practitioners for the differential diagnosis and early antimicrobial treatment of vertebral osteomyelitis.

Diabetes mellitus affects the treatment outcomes of drug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Both tuberculosis (TB) and diabetes mellitus (DM) are major public health problems threatening global health. TB patients with DM have a higher bacterial burden and affect the absorption and metabolism for anti-TB drugs. Drug-resistant TB (DR-TB) with DM make control TB more difficult. METHODS: This study was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. We searched PubMed, Excerpta Medica Database (EMBASE), Web of Science, ScienceDirect and Cochrance Library for literature published in English until July 2022. Papers were limited to those reporting the association between DM and treatment outcomes among DR-TB and multidrug-resistant TB (MDR-TB) patients. The strength of association was presented as odds ratios (ORs) and their 95% confidence intervals (CIs) using the fixed-effects or random-effects models. This study was registered with PROSPERO, number CRD: 42,022,350,214. RESULTS: A total of twenty-five studies involving 16,905 DR-TB participants were included in the meta-analysis, of which 10,124 (59.89%) participants were MDR-TB patients, and 1,952 (11.54%) had DM history. In DR-TB patients, the pooled OR was 1.56 (95% CI: 1.24-1.96) for unsuccessful outcomes, 0.64 (95% CI: 0.44-0.94) for cured treatment outcomes, 0.63 (95% CI: 0.46-0.86) for completed treatment outcomes, and 1.28 (95% CI: 1.03-1.58) for treatment failure. Among MDR-TB patients, the pooled OR was 1.57 (95% CI: 1.20-2.04) for unsuccessful treatment outcomes, 0.55 (95% CI: 0.35-0.87) for cured treatment outcomes, 0.66 (95% CI: 0.46-0.93) for treatment completed treatment outcomes and 1.37 (95% CI: 1.08-1.75) for treatment failure. CONCLUSION: DM is a risk factor for adverse outcomes of DR-TB or MDR-TB patients. Controlling hyperglycemia may contribute to the favorite prognosis of TB. Our findings support the importance for diagnosing DM in DR-TB /MDR-TB, and it is needed to control glucose and therapeutic monitoring during the treatment of DR-TB /MDR-TB patients.

Analysis of risk factors for deep vein thrombosis after spinal infection surgery and construction of a nomogram preoperative prediction model.

Objective: To investigate the differences in postoperative deep venous thrombosis (DVT) between patients with spinal infection and those with non-infected spinal disease; to construct a clinical prediction model using patients' preoperative clinical information and routine laboratory indicators to predict the likelihood of DVT after surgery. Method: According to the inclusion criteria, 314 cases of spinal infection (SINF) and 314 cases of non-infected spinal disease (NSINF) were collected from January 1, 2016 to December 31, 2021 at Xiangya Hospital, Central South University, and the differences between the two groups in terms of postoperative DVT were analyzed by chi-square test. The spinal infection cases were divided into a thrombotic group (DVT) and a non-thrombotic group (NDVT) according to whether they developed DVT after surgery. Pre-operative clinical information and routine laboratory indicators of patients in the DVT and NDVT groups were used to compare the differences between groups for each variable, and variables with predictive significance were screened out by least absolute shrinkage and operator selection (LASSO) regression analysis, and a predictive model and nomogram of postoperative DVT was established using multi-factor logistic regression, with a Hosmer- Lemeshow goodness-of-fit test was used to plot the calibration curve of the model, and the predictive effect of the model was evaluated by the area under the ROC curve (AUC). Result: The incidence of postoperative DVT in patients with spinal infection was 28%, significantly higher than 16% in the NSINF group, and statistically different from the NSINF group (P < 0.000). Five predictor variables for postoperative DVT in patients with spinal infection were screened by LASSO regression, and plotted as a nomogram. Calibration curves showed that the model was a good fit. The AUC of the predicted model was 0.8457 in the training cohort and 0.7917 in the validation cohort. Conclusion: In this study, a nomogram prediction model was developed for predicting postoperative DVT in patients with spinal infection. The nomogram included five preoperative predictor variables, which would effectively predict the likelihood of DVT after spinal infection and may have greater clinical value for the treatment and prevention of postoperative DVT.

A predictive model for early clinical diagnosis of spinal tuberculosis based on conventional laboratory indices: A multicenter real-world study.

Background: Early diagnosis of spinal tuberculosis (STB) remains challenging. The aim of this study was to develop a predictive model for the early diagnosis of STB based on conventional laboratory indicators. Method: The clinical data of patients with suspected STB in four hospitals were included, and variables were screened by Lasso regression. Eighty-five percent of the cases in the dataset were randomly selected as the training set, and the other 15% were selected as the validation set. The diagnostic prediction model was established by logistic regression in the training set, and the nomogram was drawn. The diagnostic performance of the model was verified in the validation set. Result: A total of 206 patients were included in the study, including 105 patients with STB and 101 patients with NSTB. Twelve variables were screened by Lasso regression and modeled by logistic regression, and seven variables (TB.antibody, IGRAs, RBC, Mono%, RDW, AST, BUN) were finally included in the model. AUC of 0.9468 and 0.9188 in the training and validation cohort, respectively. Conclusion: In this study, we developed a prediction model for the early diagnosis of STB which consisted of seven routine laboratory indicators.

Clinical application value of metagenomic next-generation sequencing in the diagnosis of spinal infections and its impact on clinical outcomes.

This study aimed to evaluate the impact of precise treatment administered according to the results of metagenomic next-generation sequencing (mNGS) on the clinical outcomes of patients with spinal infections. In this multicenter retrospective study, the clinical data of 158 patients with spinal infections who were admitted to Xiangya Hospital Central South University, Xiangya Boai Rehabilitation Hospital, The First Hospital of Changsha, and Hunan Chest Hospital from 2017 to 2022 were reviewed. Among these 158 patients, 80 patients were treated with targeted antibiotics according to the mNGS results and were assigned to the targeted medicine (TM) group. The remaining 78 patients with negative mNGS results and those without mNGS and negative microbial culture results were treated with empirical antibiotics and assigned to the empirical drug (EM) group. The impact of targeted antibiotics based on the mNGS results on the clinical outcomes of patients with spinal infections in the two groups was analyzed. The positive rate of mNGS for diagnosing spinal infections was significantly higher than that of microbiological culture (X 2=83.92, P<0.001), procalcitonin (X 2=44.34, P<0.001), white blood cells (X 2=89.21, P < 0.001), and IGRAs (Interferon-gamma Release Tests) (X 2 = 41.50, P < 0.001). After surgery, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) showed a decreasing trend in the patients with spinal infections in both the TM and EM groups. The decrease in CRP was more obvious in the TM group than in the EM group at 7, 14 days, 3, and 6 months after surgery (P<0.05). The decrease in ESR was also significantly obvious in the TM group compared with the EM group at 1 and 6 months after surgery (P<0.05). The time taken for CRP and ESR to return to normal in the TM group was significantly shorter than that in the EM group (P<0.05). There was no significant difference in the incidence of poor postoperative outcomes between the two groups. The positive rate of mNGS for the diagnosis of spinal infection is significantly higher than that of traditional detection methods. The use of targeted antibiotics based on mNGS results could enable patients with spinal infections to achieve a faster clinical cure.

Analysis of the diagnostic efficacy of the QuantiFERON-TB Gold In-Tube assay for preoperative differential diagnosis of spinal tuberculosis.

Background: Differential diagnosis of spinal tuberculosis is important for the clinical management of patients, especially in populations with spinal bone destruction. There are few effective tools for preoperative differential diagnosis in these populations. The QuantiFERON-TB Gold In-Tube (QFT-GIT) test has good sensitivity and specificity for the diagnosis of tuberculosis, but its efficacy in preoperative diagnosis of spinal tuberculosis has rarely been investigated. Method: A total of 123 consecutive patients with suspected spinal tuberculosis hospitalized from March 20, 2020, to April 10, 2022, were included, and the QFT-GIT test was performed on each patient. We retrospectively collected clinical data from these patients. A receiver operating characteristic (ROC) curve was plotted with the TB Ag-Nil values. The cutoff point was calculated from the ROC curve of 61 patients in the study cohort, and the diagnostic validity of the cutoff point was verified in a new cohort of 62 patients. The correlations between TB Ag-Nil values and other clinical characteristics of the patients were analyzed. Results: Of the 123 patients included in the study, 51 had confirmed tuberculosis, and 72 had non-tuberculosis disease (AUC=0.866, 95% CI: 0.798-0.933, P<0.0001). In patients with spinal tuberculosis, the QFT-GIT test sensitivity was 92.16% (95% CI: 80.25%-97.46%), and the specificity was 67.14% (95% CI: 54.77%-77.62%). The accuracy of diagnostic tests in the validation cohort increased from 77.42% to 80.65% when a new cutoff point was selected (1.58 IU/mL) from the ROC curve of the study cohort. The TB Ag-Nil values in tuberculosis patients were correlated with the duration of the patients' disease (r=0.4148, P=0.0025). Conclusion: The QFT-GIT test is an important test for preoperative differential diagnosis of spinal tuberculosis with high sensitivity but low specificity. The diagnostic efficacy of the QFT-GIT test can be significantly improved via application of a new threshold (1.58 IU/mL), and the intensity of the QFT-GIT test findings in spinal tuberculosis may be related to the duration of a patient's disease.

Diagnostic efficiency of metagenomic next-generation sequencing on spinal infection and prognosis. / å®åŸºå› äºŒä»£æµ‹åºæŠ€æœ¯å¯¹è„ŠæŸ±æ„ŸæŸ“çš„è¯Šæ–­æ•ˆçŽ‡åŠé¢„åŽçš„å½±å“.

OBJECTIVES: Spinal infection is a rare infectious disease that is difficult to treat. The incidence of spinal infection is on the rise with the experiential use of antibiotics, the increasing incidence of drug-resistant bacteria, and the improvement of detection techniques. Traditional detection methods have limitations such as low sensitivity and long time-consuming in the diagnosis of spinal infection. In the clinical diagnosis and treatment of spinal infection, it has always been the focus and difficulty to determine the type of pathogens and to use antibiotics in a targeted manner. Many patients in the early stage of spinal infection due to the limitations of traditional detection methods cannot be quickly and accurately diagnosed, resulting in diagnosis delay, missed the best treatment time, bringing disastrous consequences to patients. There is an urgent need for a high-specificity, high-sensitivity, and time-saving test technique in clinical practice, which can simultaneously distinguish and identify the pathogen of spinal infection. Metagenomic next-generation sequencing (mNGS) is a new frontier technology emerging in recent years. It can detect all known pathogens in samples and has been used to diagnose clinically atypical and rare infectious diseases. This study aims to analyze the sensitivity of mNGS technique in diagnosing pathogens after spinal infection and its effect on prognosis. METHODS: Clinical data of 82 patients with spinal infection admitted to Xiangya Hospital of Central South University from January 2019 to December 2021 were retrospectively analyzed. Peripheral blood erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and procalcitonin (PCT) were routinely performed before surgery, and focal tissue specimens were obtained during surgery. Microbial culture, histopathological examination, and mNGS detection were performed. All patients were assigned into a targeted medication group (n=71) and an experienced treatment group (n=1) based on the results of mNGS. After regular follow-up, the sensitivity of mNGS to detect pathogens of spinal infection and its effect on prognosis were evaluated. RESULTS: The positive rate of mNGS (86.59%, 71/82) was significantly higher than that of microbial culture (18.99%, 15/79) and PCT (30.23%, 13/43). There were no significant differences in preoperative temperature, white blood cell count, neutrophil ratio, and scores of Visual Analogue Scale between the targeted medication group and the experienced treatment group. Preoperative use of antibiotics had no significant effect on the positive rate of mNGS and microbial culture (P=0.681). According to the targeted medication group, postoperative CRP and ESR showed a decreasing trend, and the ESR was significantly lower than that of the experienced treatment group at 30 days follow-up (P=0.044). CONCLUSIONS: Compared with the microbial culture or PCT, mNGS has a higher sensitivity rate to detect pathogens of spinal infection. Patients receiving targeted antibiotics based on the results of mNGS have better outcomes than those receiving the experienced medicine.

Polymorphisms of SLC11A1(NRAMP1) rs17235409 associated with and susceptibility to spinal tuberculosis in a southern Han Chinese population.

OBJECTIVE: To investigate the association between SLC11A1 (NRAMP1) rs17235409 (D543N) polymorphisms and susceptibility to spinal tuberculosis (STB) in the Han population in southern China. METHODS: This study included 227 STB patients and 516 controls. Polymorphisms of SLC11A1 rs17235409 were genotyped using a SNPscan™ kit, and the protein was detected by western blotting. RESULTS: The genotype and allele frequency distributions of SLC11A1 rs17235409 differed significantly between the STB group and the control group(χ2 = 17.650, P = 0.000). The distribution of GA genotype(GA vs. GG: P = 0.000, OR [95% CI] = 2.203[1.520-3.192] was significantly different between STB group and control group, but there was no significant difference in the distribution of AA genotypes(AA vs. GG: P = 0.889, OR [95%CI] = 0.674[0.142-3.208]). The A allele was more common in the STB group than in the control group (A vs. G: P = 0.001, OR [95%CI] = 1.767[1.273-2.452]). Under the dominant model, the GA + AA genotype was more common in the STB group than in the control group (GA + AA vs. GG: P = 0.000, OR [95%CI] = 2.067[1.438-2.971]). However, under the recessive model, there was no difference in GA + GG genotype between the STB and control groups(GA + GG vs. AA: P = 0.701, OR [95%CI] =1.772[0.373-8.409]). NRAMP1 protein expression in the STB group(n = 9) was significantly higher than that in the control group(n = 9) (t = 5.292,P = 0.001). CONCLUSIONS: Variant genotypes at the rs17235409 locus of the SLC11A1 gene are associated with STB in the southern Han Chinese population. NRAMP1 protein expression is increased in patients with spinal tuberculosis, and the presence of the A allele increases the risk of developing STB.

TGF-ß-induced CD4+ FoxP3+ regulatory T cell-derived extracellular vesicles modulate Notch1 signaling through miR-449a and prevent collagen-induced arthritis in a murine model.

CD4+FOXP3+ Treg cells are central to the maintenance of self-tolerance and can be defective in autoimmunity. In autoimmune rheumatic diseases, dysfunctional self-tolerance, is to a large extent, caused by insufficient Treg-cell activity. Although nTregs have therapeutic effects in vivo, their relative scarcity and slow rate of in vitro expansion hinder the application of nTreg therapy. It was previously reported that EVs contribute significantly to the suppressive function of FOXP3+ Treg cells. Considering that the stability and plasticity of nTregs remain major challenges in vivo, we established EVs derived from in vitro TGF-ß-induced Treg cells (iTreg-EVs) and assessed their functions in a murine model of autoimmune arthritis. The results demonstrated that iTreg-EVs preferentially homed to the pathological joint and efficiently prevented the imbalance in Th17/Treg cells in arthritic mice. Furthermore, we found that miR-449a-5p mediated Notch1 expression modulation and that miR-449a-5p knockdown abolished the effects of iTreg-EVs on effector T cells and regulatory T cells in vitro and in vivo. Taken together, our results show that iTreg-EVs control the inflammatory responses of recipient T cells through miR-449a-5p-dependent modulation of Notch1 and ameliorate the development and severity of arthritis, which may provide a potential cell-free strategy based on manipulating iTreg-EVs to prevent autoimmune arthritis.

The role of B7 family members in the generation of Immunoglobulin.

Ig is a Y-shaped protein produced by plasma cells and exerts multiple functions in humoral immunity. There are five groups of Igs including IgA, IgD, IgE, IgG, and IgM, which differ in their heavy chain class. The primary function of Igs includes the neutralization of extrinsic pathogens, agglutination of foreign cells for phagocytosis, precipitation of soluble antigens in serum, and complement fixation. The B cells activated by antigen(s) can differentiate into antibody-producing cells that are called plasma cells and usually matured in the germinal center (GC). Follicular T helper (Tfh) cells crosstalk with antigen-presenting cells and play a crucial role in the development of the GC. Moreover, Tfh cells regulate trafficking through the GC to allow formative interaction with GC B cells that ultimately results in affinity maturation, B-cell memory, and Ig class switching. The B7 family is a series of number of structurally related membrane proteins that bind with a specific receptor to deliver costimulatory or co-inhibitory signals that regulate the activation of T cells in GC. Here, we review and summarize the recent advance of the effects of B7 family members on Ig production and relative diseases.

High salt diet accelerates the progression of murine lupus through dendritic cells via the p38 MAPK and STAT1 signaling pathways.

The increased incidence of systemic lupus erythematosus (SLE) in recent decades might be related to changes in modern dietary habits. Since sodium chloride (NaCl) promotes pathogenic T cell responses, we hypothesize that excessive salt intake contributes to the increased incidence of autoimmune diseases, including SLE. Given the importance of dendritic cells (DCs) in the pathogenesis of SLE, we explored the influence of an excessive sodium chloride diet on DCs in a murine SLE model. We used an induced lupus model in which bone marrow-derived dendritic cells (BMDCs) were incubated with activated lymphocyte-derived DNA (ALD-DNA) and transferred into C57BL/6 recipient mice. We observed that a high-salt diet (HSD) markedly exacerbated lupus progression, which was accompanied by increased DC activation. NaCl treatment also stimulated the maturation, activation and antigen-presenting ability of DCs in vitro. Pretreatment of BMDCs with NaCl also exacerbated BMDC-ALD-DNA-induced lupus. These mice had increased production of autoantibodies and proinflammatory cytokines, more pronounced splenomegaly and lymphadenopathy, and enhanced pathological renal lesions. The p38 MAPK-STAT1 pathway played an important role in NaCl-induced DC immune activities. Taken together, our results demonstrate that HSD intake promotes immune activation of DCs through the p38 MAPK-STAT1 signaling pathway and exacerbates the features of SLE. Thus, changes in diet may provide a novel strategy for the prevention or amelioration of lupus or other autoimmune diseases.

First case in China of vaccine-associated poliomyelitis after sequential Inactivated and bivalent oral polio vaccination.

A 16 week newborn vaccinated with bOPV 4 weeks after his first routine IPV vaccination. Nineteen days later, asymmetrical paralysis was developed on his legs, and it was diagnosed to be VAPP. Perianal abscess is suspected to be a risk factor based on some limited results of retrospective studies in China. This is a risk factor similar to the multiple intramuscular injections found by researchers in last century. The two risk factors remind us that, apart from the routine infection route of the fecal to mouth and intestinal tract, skin injury (ulceration) exposure pathway should not be ignored as another possible way of causing polio, for the local injury and lesions of the skin may increase the possibility of oral poliovirus vaccine's entry into the body. As a result, to further reduce the incidence of VAPP, bOPV should be avoided for perianal abscess. If there is perianal abscess, skin injury, or if injection is unavoidable after bOPV vaccination of an infant, much attention should be paid to the treatment and cleaning of infant feces.

Impact of university attributes on measles vaccination in universities and colleges in China / 中国学校卫生

Objective@#To understand reason for the difference of supplementary immunization activities (SIA) using measles-containing vacline (MV) among different types of universities in China.@*Methods@#Ten universities from one city were selected by using purposive sampling method. Qualitative interviews were conducted on the implementation of MV SIA in universities, and the differences of measles vaccination and the reasons were analyzed.@*Results@#The MV vaccination rates in the 10 universities in 2017 were 54%, 96%,95%,97%,81%,93%,13%,12%,10% and 21% respectively.The rate of four-year universities was higher than that of three-year colleges; and the rate of public universities was higher than that of private schools; the rate of provincial universities was higher than that of central government administered universities; the vaccination rates also vary within central government administered universities.The level, ownership and affiliation of colleges and universities led to the differences in medical qualification, administrators’ risk perception of disease and vaccines, and the relationship between the schools and local CDC, which in turn affected the implementation of vaccination in universities.@*Conclusion@#The different attributes of universities are the fundamental reasons that lead to the differences in the rate of MV SIA in Chinese universities. It is suggested that the differences of university attributes should be considered in the process of implementation of the policy of immunization in universities.And the vaccination policy in universities should be strengthened, the risk communication of universities, especially private universities, should be improved, and the working relationship of the Ministry of Health and the Ministry of Education should be enhanced.

Gaps in the 2010 measles SIA coverage among migrant children in Beijing: evidence from a parental survey.

China suffers from high incidence of measles partly due to high population mobility and low vaccination rates among migrants. In this study, we assessed the vaccination coverage of the nationwide measles supplementary immunization activity (SIA) of 2010 and its determinants among migrant children in Beijing. Information was collected through face-to-face interviews with the caregivers of 589 migrant children at train and long-distance bus stations in January 2011, when migrants were traveling home for the Chinese New Year holiday. We estimated that 83.4% of migrant children aged 8 months to 14 years received the measles vaccine during the SIA. This estimated coverage is lower than the official report of 96% among all eligible children in Beijing. Factors associated with being unvaccinated through the SIA included children being at home or in the kindergarten, living in a single-child family, and having a parent who was unaware of the SIA or who had a low level of trust in the government-administered measles campaign. We recommend more focused targeting on migrant children in future measles vaccination campaigns, improved immunization service delivery in unregulated migrant-run kindergartens and at the community level, as well as development of more effective communication methods to reach disadvantaged migrants.