OBJECTIVE: To investigate the diagnostic efficacy of ^99mTc-MDP three-phase bone scintigraphy (TPBS) combined with C-reactive protein (CRP) for periprosthetic joint infection (PJI). METHODS: The clinical data of 198 patients who underwent revision surgery of artificial joint between January 2017 and January 2024 and received TPBS examination before surgery were retrospectively analyzed. There were 77 males and 121 females with an average age of 63.74 years ranging from 24 to 92 years. There were 90 cases of hip arthroplasty and 108 cases of knee arthroplasty. PJI was diagnosed according to the 2013 American Musculoskeletal Infection Society (MSIS) standard diagnostic criteria. The sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predict value (PPV) were calculated. The receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of the three methods, and the area under curve (AUC) was used to evaluate the diagnostic performance. RESULTS: According to the 2013 MSIS criteria, 116 cases were diagnosed as PJI, and the remaining 82 cases were aseptic loosening. The cases of PJI diagnosed by TPBS, CRP, and TPBS-CRP were 125, 109, and 137 respectively, and the cases of aseptic loosening were 73, 89, and 61 respectively. The sensitivity, accuracy, NPV, and PPV of TPBS-CRP combination in the diagnosis of PJI were higher than those of TPBS and CRP, but the specificity was lower than that of TPBS and CRP. ROC curve analysis further showed that the AUC value of TPBS-CRP combination was better than that of TPBS and CRP. The severity of bone defect and the duration of symptoms in patients with false positive TPBS diagnosis were worse than those in patients with true negative TPBS diagnosis (P<0.05), but there was no significant difference in the survival time of prosthesis between the two groups (P>0.05). Among the patients diagnosed with PJI by TPBS, CRP, and TPBS-CRP, 49, 35, and 54 patients had received antibiotic treatment 2 weeks before diagnosis, respectively. There was no significant difference in the diagnostic accuracy of TPBS and TPBS-CRP before diagnosis between patients treated with and without antibiotics and those not treated (P>0.05). The diagnostic accuracy of antibiotic therapy before CRP diagnosis was significantly lower than that of untreated patients (P<0.05). CONCLUSION TPBS and CRP have limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP combination diagnostic method can synergize the local bone metabolic characteristics and systemic inflammatory response to achieve higher diagnostic accuracy, but caution should be exercised in patients with severe bone defects and longer symptom duration.
Humans ; Prosthesis-Related Infections/blood* ; Middle Aged ; Male ; Female ; Aged ; C-Reactive Protein/metabolism* ; Retrospective Studies ; Adult ; Radionuclide Imaging/methods* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged, 80 and over ; Technetium Tc 99m Medronate ; Arthroplasty, Replacement, Hip/adverse effects* ; Sensitivity and Specificity ; Knee Prosthesis/adverse effects* ; ROC Curve ; Reoperation ; Radiopharmaceuticals ; Young Adult

Humans ; Tenofovir/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Hepatitis B virus ; Viral Load ; Liver Neoplasms/drug therapy* ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Treatment Outcome

BACKGROUND: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. METHODS: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). CONCLUSIONS Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

Humans ; Tenofovir/therapeutic use* ; Emtricitabine/therapeutic use* ; HIV Infections/drug therapy* ; Anti-HIV Agents/therapeutic use*

Humans ; HIV Infections/drug therapy* ; HIV-1/genetics* ; Tenofovir/therapeutic use* ; Anti-HIV Agents/therapeutic use* ; RNA ; Drug Combinations

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans ; Antiretroviral Therapy, Highly Active/adverse effects* ; Anti-HIV Agents/adverse effects* ; HIV Infections/drug therapy* ; Tenofovir/therapeutic use* ; Retrospective Studies ; Emtricitabine/pharmacology* ; Adenine/therapeutic use* ; Lipids

OBJECTIVE: To explore the effects of oral exposure to titanium dioxide nanoparticles (TiO₂ NPs) on the composition and structure of human gut microbiota. METHODS: The particle size, shape, crystal shape and degree of agglomeration in ultrapure water of TiO₂ NPs were characterized. The in vitro human digestive tract microecological simulation system was established by simulating the fluid environment and physical conditions of stomach, small intestine and colon, and the stability of the simulation system was evaluated. The bacterial communities were extracted from human feces and cultured stably in the simulated system. They were exposed to 0, 20, 100 and 500 mg/L TiO₂ NPs, respectively, and the bacterial fluids were collected after 24 h of exposure. The effect of TiO₂ NPs on the composition and structure of human gut microbiota was analyzed by 16S rRNA sequencing technology. Linear discriminant analysis effect size (LEfSe) was used to screen differential bacteria, and the Kyoto encyclopedia of genes and genomes (KEGG) database for functional prediction. RESULTS: The spherical and anatase TiO₂ NPs were (25.12±5.64) nm in particle size, while in ultra-pure water hydrated particle size was (609.43±60.35) nm and Zeta potential was (-8.33±0.22) mV. The in vitro digestive tract microecology simulation system reached a relatively stable state after 24 hours, and the counts of Enterococci, Enterobacte-rium, and Lactobacillus reached (1.6±0.85)×10⁷, (5.6±0.82)×10⁷ and (2.7±1.32)×10⁷, respectively. 16S rRNA sequencing results showed that compared with the control group, the number and evenness of gut microbiota were not significantly affected at phylum, class, order, family and genus levels in TiO₂ NPs groups (20, 100 and 500 mg/L). The relative abundance of some species was significantly changed, and a total of 42 different bacteria were screened between the TiO₂ NPs groups (20, 100 and 500 mg/L) and the control group [linear discriminant analysis(LDA) score>3], represented by Enterobacter, Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae and Clostridium. Further predictive analysis of gut microbiota function showed that TiO₂ NPs might affect oxidative phosphorylation, energy meta-bolism, phosphonate and phosphonate metabolism, and methane metabolism (P < 0.05). CONCLUSION In human digestive tract microecological simulation system, TiO₂ NPs could significantly change the composition and structure of human gut microbiota, represented by Enterobacter and probiotics, and may further affect a variety of metabolism and function of the body.
Bacteria/genetics* ; Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; Nanoparticles ; Organophosphonates/pharmacology* ; RNA, Ribosomal, 16S ; Titanium/pharmacology* ; Water/pharmacology*

OBJECTIVES: Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF. METHODS: The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．. RESULTS: After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m²) vs (82.68±26.32) mL/(min·1.73 m²), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group. CONCLUSIONS TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.
Acute-On-Chronic Liver Failure/drug therapy* ; Alanine/therapeutic use* ; Antiviral Agents/therapeutic use* ; Guanine/analogs & derivatives* ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/drug therapy* ; Humans ; Tenofovir/analogs & derivatives* ; Treatment Outcome

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.
Alanine Transaminase ; Antiviral Agents/therapeutic use* ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Humans ; Retrospective Studies ; Tenofovir/therapeutic use* ; Treatment Outcome

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
Adenine/therapeutic use* ; Adult ; Alanine ; Alkynes ; Anti-HIV Agents/adverse effects* ; Benzoxazines ; Central Nervous System ; Cobicistat/therapeutic use* ; Cyclopropanes ; Drug Combinations ; Emtricitabine/therapeutic use* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Prospective Studies ; Quality of Life ; Quinolones ; Sleep Quality ; Tenofovir/analogs & derivatives*