Discordant results between Xpert MTB/RIF assay and Bactec MGIT 960 culture system regarding the detection of rifampin-resistant Mycobacterium tuberculosis isolates in Wenzhou, China.

This study aimed to assess the possible causes of discordant results between Xpert MTB/RIF (Xpert) and Bactec MGIT 960 Culture System (MGIT960) regarding rifampicin (RIF) susceptibility in Mycobacterium tuberculosis. Patients with previous RIF-resistant tuberculosis who were admitted to Wenzhou Central Hospital from January 2020 to December 2022 were enrolled. The isolates obtained from these patients were subjected to RIF susceptibility tests using Xpert and MGIT960, and the minimum inhibitory concentration (MIC) of RIF was determined by the MYCOTB MIC plate test. Additionally, molecular docking and molecular dynamics (MD) simulations were performed to evaluate the binding efficacy of rpoB and RIF based on rpoB mutations detected in the isolates with discordant RIF susceptibility results. A total of 28 isolates with discordant RIF susceptibility test results were detected, 15 of them were RIF susceptible with MICs ≤ 0.5 µg/mL. Twelve out of 15 isolates contained borderline RIF resistance-associated mutations [L430P (n = 6), H445N (n = 6)], 1 isolate had D435Y and Q429H double mutation, and the remaining 2 isolates had a silent (Q432Q) mutation. Compared with the affinity of RIF toward the wild type (WT) (-45.83 kcal/mol) by MD, its affinity toward L452P (-55.52 kcal/mol), D435Y (-47.39 kcal/mol), L430P (approximately -69.72 kcal/mol), H445N (-49.53 kcal/mol), and Q429H (-55.67 kcal/mol) increased. Borderline RIF resistance-associated mutations were the main cause for the discordant RIF susceptibility results between Xpert and MGIT960, and the mechanisms of the resistance need further investigated.IMPORTANCEThis study is aimed at assessing discordant results between Xpert MTB/RIF (Xpert) assay and Bactec MGIT 960 Culture System (MGIT960) regarding the detection of rifampicin (RIF)-resistant Mycobacterium tuberculosis isolates in Wenzhou, China. The discordant results of RIF between these two assays were mainly caused by borderline RIF resistance-associated mutations, subsequently by silent mutations of rpoB. Borderline RIF resistance- associated mutations detected in our study were demonstrated to not be affected by the affinity of rpoB and RIF by molecular dynamics, and the mechanism of resistance was needed to be clarified. For the discordant results of RIF by Xpert and MGIT960 that occurred, rpoB DNA sequencing was recommended to investigate its association with resistance to RIF.

Study on the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.

Objective: To evaluate the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A. Methods: According to a random sequence generated by computer software, 200 patients with confirmed influenza A were divided into a study group and a control group with 100 cases in each group. Group allocation was concealed using sealed envelopes. The study group was treated with oral administration of baloxavir marboxil tablets, 40 mg once. The control group was given oral oseltamivir capsules, 75 mg twice a day, for five consecutive days. The therapeutic effects, symptom disappearance time and adverse drug reactions of the two groups after 5 days of treatment were compared. Results: There was no significant difference in the total effective rate between the two groups (99% vs. 98%, p > 0.05). There was no significant difference in fever subsidence time (1.54 ± 0.66 d vs. 1.67 ± 0.71 d, p > 0.05), cough improvement time (2.26 ± 0.91 d vs. 2.30 ± 0.90 d, p > 0.05) and sore throat improvement time (2.06 ± 0.86 d vs. 2.09 ± 0.83 d, p > 0.05) between the two groups. There was no significant difference in the incidence of adverse drug reactions between the two groups (8% vs. 13%, p > 0.05). Conclusion: Baloxavir marboxil tablets can be effectively used in the treatment of patients with influenza A and have a similar efficacy and safety profile as oseltamivir capsules.

Oral VV116 versus placebo in patients with mild-to-moderate COVID-19 in China: a multicentre, double-blind, phase 3, randomised controlled study.

BACKGROUND: Spread of SARS-CoV-2 led to a global pandemic, and there remains unmet medical needs in the treatment of Omicron infections. VV116, an oral antiviral agent that has potent activity against SARS-CoV-2, was compared with a placebo in this phase 3 study to investigate its efficacy and safety in patients with mild-to-moderate COVID-19. METHODS: This multicentre, double-blind, phase 3, randomised controlled study enrolled adults in hospitals for infectious diseases and tertiary general hospitals in China. Eligible patients were randomly assigned in a 1:1 ratio using permuted block randomisation to receive oral VV116 (0·6 g every 12 h on day 1 and 0·3 g every 12 h on days 2-5) or oral placebo (on the same schedule as VV116) for 5 days. Randomisation stratification factors included SARS-CoV-2 vaccination status and the presence of high-risk factors for progression to severe COVID-19. Inclusion criteria were a positive SARS-CoV-2 test, an initial onset of COVID-19 symptoms 3 days or less before the first study dose, and a score of 2 or more for any target COVID-19-related symptoms in the 24 h before the first dose. Patients who had severe or critical COVID-19 or who had taken any antiviral drugs were excluded from the study. The primary endpoint was the time to clinical symptom resolution for 2 consecutive days. Efficacy analyses were performed on a modified intention-to-treat population, comprising all patients who received at least one dose of VV116 or placebo, tested positive for SARS-CoV-2 nucleic acid, and did not test positive for influenza virus before the first dose. Safety analyses were done on all participants who received at least one dose of VV116 or placebo. This study was registered with ClinicalTrials.gov, NCT05582629, and has been completed. FINDINGS: A total of 1369 patients were randomly assigned to treatment groups and 1347 received either VV116 (n=674) or placebo (n=673). At the interim analysis, VV116 was superior to placebo in reducing the time to sustained clinical symptom resolution among 1229 patients (hazard ratio [HR] 1·21, 95% CI 1·04-1·40; p=0·0023). At the final analysis, a substantial reduction in time to sustained clinical symptom resolution was observed for VV116 compared with placebo among 1296 patients (HR 1·17, 95% CI 1·04-1·33; p=0·0009), consistent with the interim analysis. The incidence of adverse events was similar between groups (242 [35·9%] of 674 patients vs 283 [42·1%] of 673 patients). INTERPRETATION: Among patients with mild-to-moderate COVID-19, VV116 significantly reduced the time to sustained clinical symptom resolution compared with placebo, with no observed safety concerns. FUNDING: Shanghai Vinnerna Biosciences, Shanghai Science and Technology Commission, and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Relevance of NAT2 genotype and clinical factors to risk for antituberculosis drug-induced liver injury.

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

N-acetyltransferase 2 genetic polymorphisms and anti-tuberculosis-drug-induced liver injury: a correlation study.

Background: Considering the genetic characteristics of people with anti-tuberculosis (TB)-drug-induced liver injury (ATDILI), genetic factors and their consequences for treatment need to be studied. Objective: The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. Methods: In this study, the liver and coagulation functions of 120 patients with TB were monitored dynamically for at least 3 months. The genetic polymorphisms of patients were detected by pyrosequencing, and the acetylation types of liver damage and the distribution of NAT2 genetic polymorphisms were compared and analysed. Results: The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups (p < 0.05). In patients with grade 4 liver injury (liver failure), any two alleles were included, i.e., *6 and *7. Specifically, patients with fast acetylation genotypes accounted for 42.4% (14/33), those with intermediate acetylated genotypes accounted for 55.2% (32/58), and patients with slow acetylation genotypes accounted for 65.5% (19/29). Conclusion: Patients with slow acetylation genotypes had higher rates of liver failure and liver injury than those with intermediate and fast acetylation genotypes, and patients with slow acetylation genotypes containing any two alleles (*6 and *7) had a higher rate of liver failure than those with other alleles. In summary, the time of liver injury in patients with slow acetylation genotypes was earlier than the total average time, and the time of liver function recovery in patients with fast acetylation genotypes was shorter than the total average time.

Strain Identification and Drug Resistance Analysis of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry in Nontuberculous Mycobacterial Lung Disease.

Objective: To evaluate the clinical value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detecting Nontuberculous mycobacteria (NTM). Methods: The clinical data of 172 patients with suspected NTM lung disease were collected from our hospital from January 1, 2018, to December 30, 2021. The results were compared with those of BACTEC MGIT 960 in liquid culture and gene chip. This study also utilised MALDI-TOF MS to detect macrolide (MA) and amikacin (Am) mutations. Results: One hundred thirty-seven cases of NTM pulmonary disease were confirmed by identifying the NTM gene chip in bronchoalveolar lavage fluid and/or MALDI-TOF MS detection. The positive predictive value and negative predictive value were 100% (131/131) and 85.37% (35/41), respectively, and the consistency of the two methods was high (kappa=0.899). For the drug resistance detection of MAs, the consistency rate between MALDI-TOF MS detection and drug sensitivity detection was 97.71% (128/131), the sensitivity was 81.25% (13/16) and the specificity was 100% (115/115). The positive and negative predictive values were 100% (13/13) and 93.75% (115/118), respectively. There was no coincidental consistency between the two methods, and the consistency was high (P<0.001, kappa=0.884). For the drug resistance test of Am, the consistency rate between the MALDI-TOF MS test and the drug sensitivity test was 93.13% (122/131), the sensitivity was 93.52% (101/108), the specificity was 90.91% (21/23) and the positive predictive value and negative predictive value were 98.06% (101/103) and 75.00% (21/28), respectively. The two methods had high consistency, and the consistency was not coincidental (P<0.001, kappa=0.781). Conclusion: Utilising MALDI-TOF MS has a good consistency with the drug resistance gene chip method and can be a rapid and effective method to identify strains and drug resistance of NTM. Therefore, it has certain clinical application value in patients with suspected NTM lung disease.

Incidence, causes, and risk factors for unplanned readmission in patients admitted with pulmonary tuberculosis in China.

INTRODUCTION: To investigate the incidence, causes, and risk factors for unplanned readmission within 30 days of discharge in patients with pulmonary tuberculosis (TB). METHODOLOGY: The clinical data of 1,062 patients with confirmed pulmonary TB who were admitted to our hospital from October 2018 to October 2021 were analysed retrospectively. The subjects were divided into a readmission group (354 cases) and a non-readmission group (708 cases) according to whether there was an unplanned admission within 30 days of discharge. We analysed the risk factors for unplanned readmission within 30 days after discharge with pulmonary TB. RESULTS: The incidence of unplanned readmission in patients with pulmonary TB was 5.2%. Being female (OR = 0.63, 95% CI: 0.434-0.942) and living in cities (OR = 0.218, 95% CI: 0.151-0.315) were protective factors for the readmission of patients with TB (p < 0.05). However, being ≥ 65 years old (OR = 2.574, 95% CI: 1.709-3.870), being a smoker (OR = 2.773, 95% CI: 1.751-4.390), having chronic obstructive pulmonary disease (COPD) (OR = 3.373, 95% CI: 1.708-6.660), having viral hepatitis (OR= 2.079, 95% CI: 1.067-4.052), receiving non-standard treatment (OR = 15.620, 95% CI: 10.413-23.431), having medical side effects (OR = 6.138, 95% CI: 3.798-9.922) and l unauthorised discharge (OR = 2.570, 95% CI: 1.509-4.376) were risk factors for the readmission to hospital of patients with TB (p < 0.05). CONCLUSIONS: Gender, age, place of residence, smoking, COPD, hepatitis, non-standard treatment, adverse drug reactions and unauthorised discharge were risk factors of TB for unplanned readmission.

Efficacy and safety of Nirmatrelvir/Ritonavir for treating the Omicron variant of COVID-19.

Objective: To evaluate the efficacy and safety of Nirmatrelvir/Ritonavir in the treatment of the Omicron variant of coronavirus disease 2019 (COVID-19). Methods: Data from 58 patients who were infected with the Omicron variant of COVID-19 were retrospectively collected. The patients were divided into two groups according to the treatment regimen they received. Patients in both groups were given Lianhua Qingwen capsules orally, three times/day, 6 g/time. The study group was given Nirmatrelvir 300 mg/Ritonavir 100 mg orally, q12h, for 5 days, and the control group was not given any antiviral drugs. The two groups were compared in terms of the change in computed tomography (CT) values of COVID-19 nucleic acid, the negative conversion time of COVID-19 RNA, hospitalization time, adverse drug reactions and COVID-19 nucleic acid re-positive tests. Results: The time to increase the CT values in the study group was faster than that in the control group, and the CT values in the study group were significantly larger than in the control group on days four and seven (p < 0.05); The negative conversion time in the study group was shorter than the control group (Z = -2.424, p = 0.015), and the hospitalization time was also shorter (Z = -2.603, p = 0.009). There were no statistically significant adverse drug reactions during hospitalization in both groups (χ2 = 2.747, p = 0.097). None of the study group tested re-positive for SARS-CoV-2 nucleic acid after discharge. Conclusion: The efficacy of Nirmatrelvir/Ritonavir in the treatment of the Omicron variant of COVID-19 was positive and had good tolerance in patients.

The diagnosis of leptospirosis complicated by pulmonary tuberculosis complemented by metagenomic next-generation sequencing: A case report.

Leptospirosis is a zoonotic infection caused by the pathogenic Leptospira. Leptospirosis is transmitted mainly through contact with contaminated rivers, lakes, or animals carrying Leptospira. Human leptospirosis has a wide range of non-specific clinical manifestations ranging from fever, hypotension, and myalgia to multi-organ dysfunction, which severely hampers the timely clinical diagnosis and treatment of leptospirosis. Therefore, there is an urgent clinical need for an efficient strategy/method that can be used for the accurate diagnosis of leptospirosis, especially in critically ill patients. Here, we report a case of a 75-year-old male patient with clinical presentation of fever, cough, and diarrhea. Initial laboratory tests and a computed tomography (CT) scan of the chest suggested only tuberculosis. The patient was finally diagnosed with pulmonary tuberculosis (PTB) combined with leptospirosis by sputum Xpert MTB RIF, epidemiological investigations, and delayed serological testing. Furthermore, through metagenomic next-generation sequencing (mNGS) of clinical samples of cerebrospinal fluid (CSF), urine, plasma and sputum, the causative pathogens were identified as Mycobacterium tuberculosis complex and Leptospira spp. With specific treatment for both leptospirosis and tuberculosis, and associated supportive care (e.g., hemodialysis), the patient showed a good prognosis. This case report suggests that mNGS can generate a useful complement to conventional pathogenic diagnostic methods through more detailed etiological screening (i.e., at the level of species or species complex).

The Relevance of Host Gut Microbiome Signature Alterations on de novo Fatty Acids Synthesis in Patients with Multi-Drug Resistant Tuberculosis.

Background: Tuberculosis (TB) is still the single pathogen infectious disease with the largest number of deaths worldwide. The relationship that intestinal microbiota disorder and de novo fatty acid synthesis metabolism have with disease progression in multi-drug resistant TB (MDR-TB) has not yet been fully studied. Objective: To investigate the effects of long periods of MDR-TB, pre-extensively drug-resistant TB (pre-XDR-TB), or rifampicin-resistant TB (RR-TB) on gut microbiome dysbiosis and advanced disease. Methods: The sample was chosen between March 2019 and September 2019 in Wenzhou Central Hospital and comprised 11 patients with pre-XDR-TB, 23 patients with RR-TB, and 28 patients with MDR-TB. Healthy individuals were chosen as the control group (CK group). An overnight fast blood sample was drawn via venipuncture into tubes without anticoagulant. For analysis, 300 mg of faeces from patients from the same group was mixed and analysed using DNA extraction, NGS sequencing, and bioinformatics. A QIAamp Fecal DNA Mini Kit was used to isolate the DNA. The extracted DNA was stored at -20°C. Results: Advanced TB was concurrent with an elevated level of the proportions of acetyl-CoA carboxylase (ACC1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fatty acid synthase (FASN) to GAPDH in de novo fatty acids synthesis, and Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus were increased significantly in RR-TB patients compared to healthy individuals, whereas their abundance in the pre-XDR-TB and MDR-TB groups showed little change in comparison with the control group. Proteobacteria levels were greatly increased in the RR-TB and MDR-TB patient groups but not in the patients with pre-XDR-TB or the healthy subjects. The pre-XDR-TB group exhibited alterations of the intestinal microbiome: coliform flora showed the highest abundance of Verrucomicrobiales, Enterobacteriales, Bifidobacteriales and Lactobacillales. De novo fatty acids synthesis was enhanced in patients and was associated with the gut microbiome dysbiosis induced by the antimicrobials, with Bacteroidetes, Bacteroidales, and Bacteroidaceae displaying the most important correlations on a phylum, order, and family level, respectively. Conclusion: The progression to advanced TB was observed to be a result of the interaction between multiple interrelated pathways, with gut-lung crosstalk potentially playing a role in patients with drug-resistant TB.

Antimicrobial susceptibility and minimum inhibitory concentration distribution of common clinically relevant non-tuberculous mycobacterial isolates from the respiratory tract.

Objective: To determine the minimum inhibitory concentration (MIC) distribution of antibacterial drugs and the susceptibility of non-tuberculous mycobacterial (NTM) isolates to provide a reference basis for the clinical selection of an effective starting regimen.Methods: The common clinical isolates of NTM in the respiratory tract, which met the standards of the American Thoracic Society for NTM lung disease, were collected. The MICs of 81 isolates were determined using the microbroth dilution method (Thermo Fisher Scientific, USA), as recommended by the Clinical and Laboratory Standards Institute, USA.Results: Included were 43 Mycobacterium avium complex (MAC) strains, 24 M. abscessus complex (MAB) strains, and 14 M. kansasii strains. The sensitivity rates of MAC to clarithromycin and amikacin were 81.4% and 79.1%, respectively, while the sensitivity rates to linezolid and moxifloxacin were only 20.9% and 9.3%; the MIC of rifabutin was the lowest (MIC50% was just 2 µg/mL). After incubation for 3-5 days, the sensitivity rate of MAB to clarithromycin was 87.5%; this decreased to 50% after 14 days' incubation. Most of them were susceptible to amikacin (91.6%), and most were resistant to moxifloxacin (95.8%), ciprofloxacin (95.8%), imipenem (95.8%), amoxicillin/clavulanate (95.8%), tobramycin (79.1%), doxycycline (95.8%) and trimethoprim/sulfamethoxazole (95.8%). intermediate (83.3%) and resistant (16.7%) to cefoxitin. The susceptibility to linezolid was only 33.3%. The sensitivity and resistance breakpoints of tigecycline were set to ≤0.5 and ≥8 µg/mL, respectively, and the sensitivity and resistance rates were 50% and 0%, respectively. M. kansasii was susceptible to clarithromycin, amikacin, linezolid, moxifloxacin, rifampicin and rifabutin (100%).Discussion: In Wenzhou, clarithromycin, amikacin and rifabutin have good antibacterial activity against MAC, while linezolid and moxifloxacin have high resistance. Amikacin and tigecycline have strong antibacterial activity against MAB, while most other antibacterial drugs are resistant to varying degrees. Most antibacterial drugs are susceptible to M. kansasii and have good antibacterial activity.Conclusion: The identification of NTM species and the detection of their MICs have certain guiding values for the treatment of NTM lung disease.Key MessageThe three most common respiratory non-tuberculous mycobacterial (NTM) isolates with clinical significance in the Wenzhou area were tested for drug susceptibility. The broth microdilution method was used to determine the minimum inhibitory concentration distribution of antibacterial drugs and the susceptibility of NTM isolates to provide a reference basis for the clinical selection of an effective starting regimen.

Clinical Manifestation, Imaging Features and Treatment Follow-up of 29 Cases with Hepatic Tubercolosis.

To understand the clinical and imaging manifestations and the treatment and follow-up of hepatic tuberculosis (HTB), we retrospectively analysed the clinical and imaging data of 29 patients with HTB who had been diagnosed clinically or by biopsy, and the clinical and imaging data had been summarised. Patient characteristics were followed up after anti-TB drug treatment. The median age of the 29 patients with HTB was 37 years, and most were male (58.6%). The patient's symptoms included fever (48.2%), respiratory symptoms (27.5%), abdominal pain (24.1%), and abdominal distension (10.3%). Elevated erythrocyte sedimentation rate (79.3%), elevated serum C-reactive protein (75.8%) and hypoalbuminemia (62.0%) were common features. Three patients were serologically positive for acquired human immunodeficiency syndrome, and two were serologically positive for hepatitis B surface antigen with normal tumour markers. The 29 patients with HTB included 17 with serous HTB, 9 with parenchymal HTB (8 with parenchymal nodular HTB and 1 with parenchymal miliary HTB), 1 with intrahepatic abscess type HTB, and 2 with hilar HTB. Approximately 86% of the patients also had pulmonary TB. Most of the serous HTB patients also had tuberculous peritonitis. Enhanced computerized tomography scans of the serous and parenchymal HTB cases showed the progressive development of lesions. Abnormal blood perfusion was observed in the hepatic artery, and the clearest evidence of TB was observed in the hepatic portal vein. Magnetic resonance imaging indicated that the lesions returned a high signal in the diffusion-weighted imaging sequence. However, the lesions' apparent diffusion coefficient values reflected high signals. The Xpert MTB/RIF test detected Mycobacterium TB complex in the liver biopsy fluid from 10 patients. Regarding histopathology, one patient showed granulomatous inflammation, and one patient's acid-fast bacillus (AFB) stain was positive. The treatment of two patients was stopped due to their adverse reactions to the drugs and the risk of creating drug-resistant TB. The remaining patients received anti-TB treatment, but one subsequently died, and two were unavailable for follow-up. The clinical symptoms of HTB are difficult to detect, and it has diverse manifestations by imaging, with no obvious specificity in terms of pathological results. Therefore, follow-up of liver lesions for checking anti-TB therapy is another method for diagnosing HTB. In addition, early active anti-TB treatment can achieve good curative results.

Efficacy and safety of Fuzheng Huayu tablet on persistent advanced liver fibrosis following 2 years entecavir treatment: A single arm clinical objective performance criteria trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Antiviral therapy can alleviate liver fibrosis in chronic hepatitis B, but it has a limited effect on advanced liver fibrosis/cirrhosis. Traditional Chinese medicine (TCM), particularly FuZheng HuaYu (FZHY) tablet, appears to have an antifibrotic effect, but its improving resolution of hepatitis b virus (HBV) -associated advanced fibrosis and experienced anti-viral treatment has not been investigated. AIM OF THE STUDY: To observe the safety and efficacy of adjunctive FZHY on the HBV-associated cirrhosis patients who received 2 years of entecavir but still with advanced fibrosis. METHODS: An open-label, multicentre, single arm trial. 251 patients were included and treated with TCM consisted of FZHY tablets 1.6 g and granules, three times a day in addition to entecavir 0.5 mg daily for an additional 48 weeks. Primary outcome was regression of fibrosis (the proportion of patients with a 1-point decrease in the Ishak liver fibrosis score from baseline to week 48). RESULTS: Fibrosis regression occurred in 94 of 184 patients with paired liver biopsy (51.09%, 95% CI: 43.9～58.0). In 132 compensated cirrhosis patients (Ishak score ≥5), 56.06% (74/132, 95% CI: 47.5～64.2) showed fibrosis regression and reached the goal of 54% (15% more than entecavir mono-therapy). 10 patients occurred adverse reaction, most of them were mild, and all recovered or achieved remission. CONCLUSIONS: The combination therapy of FZHY, TCM granules and ETV could regress the liver fibrosis in the patients with HBV cirrhosis, who experienced 2 years of ETV treatment, and it is safe and well tolerated.

The Diagnostic Value of the Thermostatic Amplification of Ribonucleic Acid in Bronchoalveolar Lavage Fluid in Smear-Negative Pulmonary Tuberculosis.

Objective: This study aimed to determine the value of the simultaneous amplification and testing for Mycobacterium tuberculosis in bronchoalveolar lavage fluid (BALF) in the diagnosis of smear-negative pulmonary tuberculosis (PTB). Methods: A total of 316 patients were selected, of which 197 had smear-negative PTB (observation group), and 119 did not have TB (control group). Bronchoscopy was performed in both groups, and BALF samples were collected for acid-fast bacilli smears, simultaneous amplification/testing for TB (SAT-TB), and BACTEC MGIT 960 cultures. The sensitivity, specificity, positive predictive, and negative predictive values of SAT-TB in BALF for the diagnosis of negative TB were calculated. Results: The sensitivity of SAT-TB detection was 45.18%, which was significantly higher than smears and slightly lower than cultures. The specificity of SAT-TB was 99.16%, which differed slightly from the other two methods. The positive predictive value was 98.89%, which was not significantly different from the other two methods. The negative predictive value of SAT-TB was 58.91%, which was higher than smears and slightly lower than cultures. Conclusion: The very high specificity and negative prediction of SAT-TB in BALF means that the method has great application value for the rapid diagnosis of smear-negative PTB.

Application of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the detection of drug resistance of Mycobacterium tuberculosis in re-treated patients.

OBJECTIVE: To evaluate the value of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in the detection of drug resistance of Mycobacterium tuberculosis in re-treated patients. METHODS: MALDI-TOF MS was used to detect the resistance of 202 cases of retreatment pulmonary tuberculosis infection strains to isoniazid (INH), rifampin (RFP), ethambutol (EMB), streptomycin (SM), ofloxacin (Ofx), moxifloxacin (Mfx), amikacin (Am), Kanamycin (Km) and capreomycin (Cm), and the results were compared with those of BACTEC 960 liquid culture detection to compare the coincidence rate of the two methods. RESULTS: MALDI-TOF MS detected 60 copies of Mtb gene mutation, and drug-resistant gene mutation strains accounted for 34.68% (60/173) of positive strains. Rifampicin-related rpoB gene mutations accounted for 86.67% (52/60), isoniazid-related katG + inhA gene mutations accounted for 80.00% (48/60) and inhA-15 gene mutations accounted for 8.33% (5/60), streptomycin-related rpsL gene mutations accounted for 28.33% (17/60), ethambutol-related embB gene mutations accounted for 45.00% (27/60), quinolone-related gyrA basic mutation accounted for 26.67% (16/60), ethyl/propylthiamine-related embB gene mutation accounted for 36.67% (22/60) and inhA-15 gene mutation accounted for 10.00% (6/60), aminoglycoside-related rrs gene mutation accounted for 26.67% (16/60), clofazimine Fazimine, bedaquiline related Rv0678 193 gene mutations accounted for 3.33% (2/60), pyrazinamide, p-aminosalicylate, linezolid were not seen mutated genes. Multi-gene mutant strains accounted for 63.33% (38/60) of drug-resistant strains. CONCLUSION: MALDI-TOF MS assay has good agreement with BACTEC960 liquid culture drug sensitivity test, which can be a rapid and effective method to screen for drug resistance of Mycobacterium tuberculosis, and has some clinical application value in patients with relapse tuberculosis.

Xpert MTB/RIF Improves the Prognosis of Multidrug-Resistant Tuberculosis Patients Through Faster Diagnosis and Earlier Targeted Treatment: A Prospective Cohort Study.

Objective: To evaluate the effectiveness of Xpert MTB/RIF in patients with multidrug-resistant tuberculosis (MDR-TB). Methods: Seventy-five patients with MDR-TB were enrolled in this prospective cohort study and were divided into two groups. The observation group were given standardized anti-MDR-TB treatment regimen (6ZAmLfxPtoCs/18ZLfxPtoCs) immediately when they had two positive sputum Xpert MTB/RIF results of RIF resistance. The control group were not given standardized anti-MDR-TB regimen until culture-based drug-susceptibility testing suggested MDR-TB. Treatment effect index, foci absorption, conversion of sputum, treatment outcomes, and adverse reactions were observed. Fisher's exact test and chi-square test were used to compare the differences between groups. Results: Treatment effect index of the observation group significantly out-performed the control group (24/34, 70.6% vs. 17/38, 44.7%, p = 0.027). At the 6th month of treatment course, observation group achieved significantly higher conversion (28/34, 82.3% vs. 23/38, 60.5%, p = 0.042). The foci absorption, cavity change, conversion at the 24th month of course, or treatment outcome between two groups were not statistically different. Conclusion: Xpert MTB/RIF helps MDR-TB patients to start rational treatment regimen earlier and reach earlier sputum conversion.

Increased levels of lactate dehydrogenase and hypertension are associated with severe illness of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is amid an ongoing pandemic. It has been shown that patients with cardiovascular comorbidities are at higher risk of severe illness of COVID-19. AIM: To find out the relationship between cardiovascular comorbidities and severe illness of COVID-19. METHODS: The clinical data of 140 COVID-19 patients treated from January 22, 2020 to March 3, 2020 at our hospital were retrospectively collected. The clinical characteristics were compared between patients with mild illness and those with severe illness. RESULTS: There were 75 male patients and 65 female patients (53.6% vs 46.4%). The mean age was 45.4 ± 14.6 years (range, 2-85 years). Most of the patients had mild illness (n = 114, 81.4%) and 26 patients had severe illness (18.6%). The most common symptom was fever (n = 110, 78.6%), followed by cough (n = 82, 58.6%) and expectoration (n = 51, 36.4%). Eight patients were asymptomatic but were positive for severe acute respiratory syndrome coronavirus 2 RNA. Patients with severe illness were significantly more likely to be hypertensive than those with mild illness [(10/26, 38.4%) vs (22/114, 19.3%), P = 0.036]. The levels of lactate dehydrogenase were significantly higher in the severe illness group than in the mild illness group (299.35 ± 68.82 vs 202.94 ± 63.87, P < 0.001). No patient died in either the severe illness or the mild illness group. CONCLUSION: Hypertension and elevated levels of lactate dehydrogenase may be associated with severe illness of COVID-19.

Correlation Analysis Between Serum Uric Acid, Prealbumin Level, Lactate Dehydrogenase, and Severity of COVID-19.

Objective: To analyze the correlation between serum uric acid, prealbumin levels, lactate dehydrogenase (LDH), and the severity of COVID-19. Methods: The data from 135 patients with COVID-19 was collected, and the patients were divided into a non-severe group (110 cases) and a severe group (25 cases), according to the severity of illness. Sixty cases with normal physical examinations over the same period and 17 cases diagnosed with other viral pneumonia in the past five years were selected as the control group to analyze the correlation between the detection index and the severity of COVID-19. Results: Serum albumin and prealbumin in the severe group were significantly lower than those in the non-severe group (p < 0.01); serum uric acid in the severe group was lower than that in the non-severe group (p < 0.05). LDH and C-reaction protein (CRP) in the severe group were higher than those in non-severe group (p < 0.01); the levels of albumin, prealbumin, serum uric acid, and LDH in the severe group were significantly different from those in healthy control group (p < 0.01) and the levels of prealbumin, serum uric acid, LDH, and CRP in the severe group were significantly different from those in the other viral pneumonia group (p < 0.01). Serum albumin and prealbumin were positively correlated with the oxygenation index (p < 0.001), while LDH was negatively correlated with oxygenation index (p < 0.001). Conclusion: Serum albumin, prealbumin, the oxygenation index, and LDH are risk factors of COVID-19.

Clinical Characteristics of Patients With Re-admitted of Novel Coronavirus 2019 (nCOVID-19) in Wenzhou, China.

Background: During the COVID-19 pandemic, many patients admitted to hospital for treatment have recovered and been discharged; however, in some instances, these same patients are re-admitted due to a second fever or a positive COVID-19 PCR test result. To ascertain whether it is necessary to treat these patients in hospitals, especially in asymptomatic cases, we summarize and analyze the clinical and treatment characteristics of patients re-admitted to hospital with a second COVID-19 infection. Methods: Of the 141 COVID-19 cases admitted to the Wenzhou Central Hospital between January 17, 2020, to March 5, 2020, which were followed until March 30, 2020, 12 patients were re-admitted with a second COVID-19 infection. Data was collected and analyzed from their clinical records, lab indexes, commuted tomography (CT), and treatment strategies. Results: Most of the 141 patients had positive outcomes from treatment, with only 12 (8.5%) being re-admitted. In this sub-group: one (8.3%) had a fever, a high white blood cell count (WBC), and progressive CT changes; and one (8.3%) had increased transaminase. The PCR tests of these two patients returned negative results. Another 10 patients were admitted due to a positive PCR test result, seven of which were clinically asymptomatic. Compared to the CT imaging following their initial discharge, the CT imaging of all patients was significantly improved, and none required additional oxygen or mechanical ventilation during their second course of treatment. Conclusions: The prognoses of the re-admitted patients were good with no serious cases. We conclude that home treatment with concentrated medical observation is a safe and feasible course of treatment if the patient returns a positive PCR test result but does not display serious clinical symptoms. During medical observation, patients with underlying conditions should remain a primary focus, but most do not need to be re-admitted to the hospital.

Epidemiological Features of 105 Patients Infected with the COVID-19.

OBJECTIVE: To investigate and evaluate the clinical features of patients infected with the 2019 novel coronavirus (COVID-19) outside of Wuhan. METHODS: 105 patients admitted to our hospital with clinical- and laboratory-confirmed COVID-19 infection were studied. Data were collected from January 17, 2020 to March 5, 2020. RESULTS: 105 patients (57 male and 48 female) were confirmed to have COVID-19 infection. Among the 105 patients, 55 (52%) had made short trips to Wuhan during the two weeks before the onset of illness, and these were the first-generation confirmed cases. An exact date of close contact with someone in Wenzhou with confirmed or suspected COVID-19 infection from Wuhan (the second-generation confirmed cases) could be provided by 38 (36%) patients. Of the remaining patients, six (6%; the third-generation confirmed cases) were familial clusters of the second-generation confirmed cases, three (3%) had no definite epidemiological features, and 16 (15%) were from the same location as for the case report. CONCLUSION: Due to the infectiousness of COVID-19, patients with infections should be diagnosed and treated as early as possible after developing fever symptoms or showing other clinical characteristics or imaging features. With respect to high-risk cases, we must focus on any complications that arise and take effective measures to treat them immediately. This will significantly improve the prognosis of patients with severe infections.