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.

Synthesis of 2,3-Dihydrothieno(2,3-b)quinolines and Thieno(2,3-b)- quinolines via an Unexpected Domino Aza-MBH/Alkylation/Aldol Reaction.

An efficient, mild, and convenient method for the preparation of 2,3-dihydrothieno(2,3-b)quinolines and thieno(2,3-b)-quinolines via an unexpected domino aza-Morita-Baylis-Hillman/alkylation/aldol reaction has been developed. The plausible mechanisms for the unexpected reaction are also given.

Enantioselective Construction of Polyfunctionalized Spiroannulated Dihydrothiophenes via a Formal Thio [3+2] Cyclization.

A formal thio [3+2] cyclization catalyzed by Takemoto's organocatalyst has been reported for the construction of optically active spiroannulated dihydrothiophenes in high yields with excellent regio-, chemo-, diastereo-, and enantioselectivities.

Advances in the study of biomarkers related to bone metastasis in breast cancer.

Breast cancer is by far the most common malignancy in females. And bone is the most common site of distant metastasis in breast cancer, accounting for about 65 to 75% of all metastatic breast cancer patients.1,2Bone metastasis is an important factor affecting the prognosis of breast cancer. When patients have early-stage breast cancer without metastasis, their 5-year survival rate is as high as 90%, and once metastasis occurs, their 5-year survival rate will drop to 10%.3 Bone radionuclide imaging (ECT), X-ray, CT scan, MRI and other imaging tests to diagnose breast cancer bone metastasis are commonly used in clinical, It is currently believed that breast cancer bone metastasis is a multistep process: first, breast cancer cells need to acquire invasive and metastatic properties; breast cancer cells enter the blood circulation and migrate from blood breast cancer cells enter the blood circulation and migrate from blood vessels to bone tissue in a targeted manner; breast cancer cells adhere and remain in bone tissue and colonise it; and finally, it leads to bone destruction.4 Several key molecules are involved in breast cancer bone metastasis, and serum biomarkers are generally able to detect pathological changes earlier Several key molecules are involved in breast cancer bone metastasis, and serum biomarkers are generally able to detect pathological changes earlier than imaging.5 This review describes the progress of serum biomarkers for breast cancer bone metastasis.

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.

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.

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.

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.

Facile domino access to chiral mono-, bi-, and tricyclic 2,3-dihydrofurans.

The asymmetric domino Michael-S(N)2 reaction of various 1,3-dicarbonyl compounds to α-bromonitroalkenes is described for the first time, employing readily available cinchona-derived bifunctional thioureas as organocatalysts. The novel transformations were highly regio-, chemo-, diastereo-, and enantioselective, which simultaneously gave the chiral tricyclic 2,3-dihydrofurans, bicyclic 2,3-dihydrofurans, and tetrasubstituted 2,3-dihydrofurans with two vicinal chiral carbon centers.

Efficient kinetic resolution of racemic 3-nitro-2H-chromene derivatives catalyzed by Takemoto's organocatalyst.

Efficient kinetic resolution of racemic 3-nitro-2H-chromenes by bifunctional thiourea afforded optically active (R)-3-nitro-2H-chromene derivatives with moderate to good enantioselectivities, which simultaneously gave the multifunctional 3,4-diphenyl-3a-nitrobenzopyrano-[3,4-c]-pyrrolidine-1,1-dicarboxylate derivatives with four vicinal chiral carbon centers.

The organocatalytic two-step synthesis of diversely functionalized tricyclic tetrazoles.

The diversely functionalized tricyclic tetrazoles were synthesised from readily available substrates via intramolecular 1,3-dipolar cycloaddition as the key step in good yields (53-78% yield for two steps) with high enantioselectivities (81-99% ee).

A convenient synthesis of (S)-H4-BINOL and its derivatives via hydrogenation of monoesters of BINOL.

A new multigram synthesis of chiral (S)-H(4)-BINOL and its derivatives in moderate to high yield (up to 83% total yield) via monoesterification of (S)-BINOL, hydrogenation, and saponification reaction was described. The two new monomethylated (S)-H(4)-BINOL obtained may be useful materials in asymmetric catalysis.

Efficient method for the synthesis of functionalized pyrazoles by catalyst-free one-pot tandem reaction of nitroalkenes with ethyl diazoacetate.

The one-pot synthesis of multisubstituted pyrazole derivatives was achieved via catalyst-free 1,3-dipolar cycloaddition of ethyl diazoacetate and nitroalkenes as the key step and elimination of the leaving group (NO(2) or Br) followed by intramolecular proton transfer with satisfactory yields.

Neurophysiological and Neuropsychological Correlates of Subconscious Auditory Processing During Anesthesia and Their Implications in Anesthesia Awareness.

Like any other unusual state of consciousness, the condition of anesthesia remains a mystery, especially regarding the information processing events of the brain. Evoked potentials are the only known way to understand the neurophysiological events of brain in this condition. Auditory evoked potentials (AEPs) have been used as a measure of the depth of anesthesia during the intra-operative process. AEPs have been classically divided, on the basis of their latency, into first, fast, middle, slow, and late components. Auditory evoked potential has been advocated for the assessment of intra-operative awareness (IOA) but has not been considered seriously enough to be universalized. It is because we have not explored enough the impact of auditory perception and auditory information processing on the IOA phenomena as well as on the subsequent psychological impact of IOA on the patient. This limitation is because we have poor understanding of the subconscious auditory processing itself. This perspective is especially important because more of the IOA phenomena exist in the subconscious domain than they do in the conscious domain of explicit recall. Two important forms of these subconscious manifestations of IOA are the implicit recall phenomena and post-operative dreams related to the operation. Here we present a review of the neurophysiological and neuropsychological correlates of auditory processing during anesthesia. We start with a brief description of auditory awareness and the factors affecting it. Further, we proceed to the evaluation of conscious and subconscious information processing by auditory modality and how they interact during and after intra-operative period. Further, we show that both conscious and subconscious auditory processing affect the IOA experience and both have serious psychological implications on the patient subsequently. These effects could be prevented using auditory evoked potential during monitoring of anesthesia, especially the midlatency auditory evoked potentials. To conclude, we propose that the use of Auditory evoked potential should be universal with general anesthesia use in order to prevent the occurrences of distressing outcomes resulting from both conscious and subconscious auditory processing during anesthesia.

Short synthesis of the CDEF ring system of lactonamycin.

[reaction: see text]. A synthesis of the CDEF fragment of lactonamycin is achieved in eight steps (six pots) from the known and readily available anhydride 4 via a Diels-Alder reaction between tricycle 13 and 2,3-dimethylbenzoquinone.