Safety of a Novel ESAT6-CFP10 skin test compared with tuberculin skin test in a double-blind, randomized, controlled study.

BACKGROUND: ESAT6-CFP10 (EC) skin test has been reported accurate and safe in identifying tuberculosis infection. We aimed to demonstrate the safety of EC skin test compared with tuberculin skin test (TST) in university freshmen. METHODS: We conducted a double-blind, randomized, controlled clinical study in a university freshmen population with 16,680 participates in China, and finally 14,579 completed the study. About a half received an EC skin test and the others received TST. Adverse reactions were evaluated. RESULTS: Out of the 14,579 participants, 48.2% (7029/14,579) were males. The average age was 18.1 ± 0.8 years and the average BMI was 20.9 ± 3.1 kg/m2. 50.4% (7351/14,579) participants received EC skin test and 49.6% (7228/14,579) received TST. The EC group had significantly less adverse reactions compared with the TST group (21.3%, 1565/7351 vs. 34.6%, 2499/7228, P = 0.000). The most common adverse reactions for EC were bleeding (5.63%, 414), dermatodyschroia (4.27%, 314), induration (3.90%, 287), swelling (2.49%, 183), pain (1.59%, 117) and pruritus (1.48%, 109). Bleeding, dermatodyschroia, swelling and erythema were significantly less in EC group (P < 0.05), while others were similar to those of TST. CONCLUSION: the EC skin test was safe in our cohort. And its incidence of total adverse drug reactions (ADRs) is less than that of TST. Most adverse reactions were mild or moderate, lasting less than 48 h and self-limiting. Considering the satisfactory diagnostic accuracy in identifying tuberculosis infection, the cost and safety, the EC skin test might be a potential candidate for replacing TST in high burden countries or those with routine BCG vaccination. CLINICAL TRIALS REGISTRATION: ChiCTR2000038622, Safety of the EC skin test to screen tuberculosis infection in two universities, compared with the tuberculin skin test: a double-blind, randomized, controlled trial. registered on 26/09/2020 at http://www.chictr.org.cn .

Sofosbuvir-based regimen is safe and effective for hepatitis C infected patients with stage 4-5 chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Whether sofosbuvir is suitable for hepatitis C virus (HCV) infected patients with severe renal impairment is inconclusive. This systematic review aims to evaluate the safety and effectiveness of SOF-based regimen in the setting of stage 4 and 5 chronic kidney disease (CKD). METHODS: We conducted a systematic literature search in PubMed, Web of Science, EMBASE and Google Scholar with searching strategy: (sofosbuvir OR Sovaldi OR Harvoni OR Epclusa OR Vosevi) AND (severe kidney impairment OR severe renal impairment OR end-stage renal disease OR dialysis OR renal failure OR ESRD OR renal insufficiency OR hepatorenal syndrome OR HRS). Sustained virological response (SVR12/24) rate and serious adverse event (SAE) rate with 95% confidence intervals were aggregated. Subgroup analysis was implemented to evaluate the impact of treatment strategy and patient characteristics. RESULTS: Twenty-one studies met inclusion criteria, totaling 717 HCV infected patients with CKD stage 4 or 5 (58.4% on dialysis). Pooled SVR12/24 was 97.1% (95% CI 93.9-99.3%), and SAE rate was 4.8% (95% CI 2.1-10.3%). There was no significant difference at SVR12/24 (97.1% vs 96.2%, p = 0.72) or SAE rate (8.8% vs 2.9%, p = 0.13) between subgroups applying full or decreased dose of sofosbuvir. Cirrhotic and non-cirrhotic patients achieved comparable sustained virological response (RR 0.93, 95% CI 0.85-1.02). Four studies reported eGFR/serum creatinine pre- and post- treatment, with no significant modification. CONCLUSIONS: Our study suggests SOF-based regimen might be used safely and effectively in patients living with HCV infection/stage 4-5 CKD, with normal and reduced dose of sofosbuvir. Prospective and well-controlled trials are needed to confirm these findings. TRIAL REGISTRATION: PROSPERO CRD42018107440 .

Neuropsychiatric events in an adult patient with influenza a (H3N2) treated with oseltamivir (Tamiflu): a case report.

BACKGROUND: Total four influenza pandemics have happened since twentieth century, and currently influenza is in the seasonal epidemic around the world, with a sharp increase in its incidence each year. As an effective treatment of influenza infection, the use of oseltamivir is climbing globally. However, there have been reports of neuropsychiatric events associated with the drug, mainly in young patients and males. To our knowledge, this is the first reported case of oseltamivir-associated neuropsychiatric events occurring in an patient over 50-year-old. CASE PRESENTATION: Here we present the case of a 57-year-old Chinese female with H3N2 influenza infection who developed abnormal psychiatric symptoms after administration of high doses of oseltamivir. The patient recovered completely within the cessation of oseltamivir. CONCLUSIONS: We hope that our case report will lead clinicians to be mindful about oseltamivir's potential neuropsychiatric side effects, and to pay special attention to each patient's mental state, both in children and adults.

Experience in the diagnosis and treatment of pneumonia caused by infection with Tropheryma whipplei: A case series.

Tropheryma whipplei (TW) is the root cause of Whipple's disease (WD), a rare infectious illness leading to multi-organ impairment. A prominent feature of WD is acute pneumonia, which can be exceedingly challenging to diagnose clinically due to the pathogen's surreptitious nature. However and significantly, with the advent of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF), it offers clinicians a potent tool at their disposal to detect TW infections. The present study conducted a retrospective analysis of clinical data gleaned from five patients in Hunan Province in China. Findings in this study demonstrated the potential of BALF-mNGS in diagnosing pneumonia caused by TW infection.

Diagnosis of extrapulmonary tuberculosis by ultrasound-guided biopsy: A retrospective comparison study.

Objective: To compare the diagnostic performance of laboratory assays on the ultrasound-guided core needle biopsy samples for diagnosis of extra-pulmonary tuberculosis (EPTB) in HIV-positive and HIV-negative patients. Methods: A total of 217 patients suspected to have EPTB underwent lesion biopsy from 2017 to 2020. Results of laboratory tests on the biopsy and non-biopsy samples were collected with clinical data for retrospective analysis of test utility. The calculated diagnostic accuracy of the tests was stratified according to the specimen types and HIV status. Results: The cohort contained 118 patients with a final positive diagnosis of extrapulmonary tuberculosis (EPTB group, 54.4%) and 99 finally diagnosed as without TB (non-EPTB group, 45.6%). The risk factor for EPTB was HIV co-infection (OR 2.22, 95% CI 1.17-4.28, p = 0.014). In biopsy samples, GeneXpert (Xpert) showed higher sensitivity (96.6% [91.6-98.7], p < 0.0001) than culture (56.1% [47.0-64.9]). Regardless of HIV status, Xpert had the highest sensitivity (>95%) and specificity (nearly 100%) of any methods. In non-biopsy samples, only T-SPOT.TB (T-SPOT) showed higher sensitivity than culture (90.9% [62.3-99.5] vs 35.3% [17.3-58.7], p = 0.0037). Furthermore, the sensitivities of Xpert were lower in non-biopsy samples (60.0% [23.1-92.9], p = 0.022) than in biopsy samples (100% [86.7-100]). Even in smear-negative biopsy samples, Xpert still had higher sensitivity than culture and retained high specificity (100% [95.7-100]). Conclusion: Superior performance of Xpert in diagnosing EPTB was observed regardless of HIV status and specimen types. Nevertheless, the biopsy samples still substantially facilitated the accurate diagnosis of extrapulmonary tuberculosis.

Duration of SARS-CoV-2 Serum-Neutralizing Antibodies Against SARS-CoV-2 Dependent on the Individual.

We investigated the persistence of SARS-CoV-2-specific neutralizing antibodies in serum (CoV-2-SNAb) against the "WH-Human 1" coronavirus in 57 convalescent persons from January 2020 to January 2021. The CoV-2-SNAb response against authentic "WH-Human 1" showed a significant (p < 0.01) neutralizing high effect (≥95%) in the following manner: by 94.7% neutralization for up to 6 months, by 73.1% for up to 8 months, and by 31.7% for up to 10 months in correlation with a significant decrease in the concentration of the virus determined by SARS-CoV-2 spike protein extracellular domain and spike-receptor-binding domain (S-RBD). There was neutralizing effect (<95%) when the S-RBD optical density (OD) value was more than 1.0, showing a suitable threshold of S-RBD = 1.0 (antibody-tittering, OD). However, in some convalescent persons, no neutralizing effect (<95%) was observed although the SARS-CoV-2-specific neutralizing antibodies were bound to the S-RBD (OD >1.0). The neutralization of the virus in these cases may not involve S-RBD, but rather B- and T cell memory responses in overall immunity, using the threshold value (OD = 1.0) of S-RBD as a simple and effective method to determine the neutralization effect of the antibody efficacy and use of vaccination in combination with a standard pseudovirus neutralizing assay. We suggest that convalescent persons should contact their physicians 6-month postinfection to test the function of their serum neutralizing antibodies and determine whether administering a SARS-CoV-2 vaccine is necessary to prevent the development of severe illness in the future.

The effect of BCG vaccination and risk factors for latent tuberculosis infection among college freshmen in China.

OBJECTIVES: In this study, we aimed to verify whether Bacillus Calmette-Guérin (BCG) can protect first-year college students against Mycobacterium tuberculosis (MTB) infection by the recombinant fusion protein ESAT6-CFP10 skin test (ECST) or the tuberculin skin test (TST). METHODS: We conducted a cross-sectional study to assess risk factors for latent tuberculosis infection (LTBI). Vaccine effectiveness of BCG against LTBI, measured by ECST and TST separately, was assessed using multivariable logistic regression. RESULTS: A total of 7351 college freshmen accepted ECST, whereas 7228 accepted TST. A total of 263 (3.58%) tested positive with ECST and 581 (8.04%) tested positive with TST. BCG was significantly associated with LTBI (ECST: adjusted odds ratio (aOR) = 0.26; 95% CI 0.09 to 0.73; TST: aOR = 0.25; 95% CI 0.13 to 0.49). The BCG protective effect on freshmen living in rural areas (ECST: aOR = 0.16; 95% CI 0.04 to 0.55; TST: aOR = 0.12; 95% CI 0.04 to 0.33) is better than that of freshmen living in cities (ECST: aOR = 0.53; 95% CI 0.07 to 4.03; TST: aOR = 0.44; 95% CI 0.17 to 1.16). CONCLUSIONS: Protection against LTBI was strongly associated with BCG vaccination. A novel skin test (ECST) may underestimate the protective effects of BCG in college freshmen. BCG has better protection in areas with a slightly higher incidence of LTBI.

Meta-analysis and systematic review of electronic bronchoscopy in refractory pneumonia.

BACKGROUND: A systematic review and meta-analysis were performed to explore the adoption value of electronic bronchoscopy (EBS) in the diagnosis and treatment of refractory pneumonia and to provide a theoretical basis for the clinical bronchoscopy treatment of patients. METHODS: Randomized controlled trials of treatment-resistant pneumonia searched on PubMed, Embase, and other websites before December 31, 2020 were collected. Literature was selected by inclusion and exclusion criteria. Bias risk was assessed using Cochrane intervention system Review manual 5.0.2 and Review Manager 5.3. RESULTS: A total of 6 articles meeting the requirements were included, comprising 796 participants. The results of meta-analysis showed that the clinical efficacy [odds ratio (OR) =3.8; 95% confidence interval (CI): 1.11-12.99; Z=2.13; P =0.03] and white blood cell counts [mean difference (MD) =0.55; 95% CI: -0.57 to 1.67; Z=0.96; P=0.34] of patients both increased. The mortality rate (OR =0.7; 95% CI: 0.3-1.63; Z=0.82; P=0.41), the incidence of infection (OR =0.84; 95% CI: 0.5-1.39; Z=0.69; P=0.49), ICU hospitalization days (OR =0.59; 95% CI: 0.36-0.98; Z=2.04; P=0.04), days of antibiotic use (OR =0.39; 95% CI: 0.18-0.84; Z=2.41; P=0.02), body temperature (MD =-0.2; 95% CI: -0.24 to 0.16; Z=9.5; P<0.0001), and the PaO2:FIO2 ratio (MD =-9.96; 95% CI: -13.31 to -6.61; Z=5.83; P<0.0001) of patients in the experimental group were lower than those of the control group. Differences in white blood cell count, mortality rate, and incidence of infection of patients in the experimental group were not statistically significant compared with those in the control group. DISCUSSION: EBS adopted in the diagnosis and treatment of refractory pneumonia can reduce the occurrence of postoperative adverse reactions, reduce the infection rate, and effectively improve the clinical symptoms. It is therefore suitable for the treatment of this disease.

Clinical Characteristics and Prognosis of 218 Patients With COVID-19: A Retrospective Study Based on Clinical Classification.

Background: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has spread worldwide. Methods: This was a retrospective case series involving 218 patients admitted to three tertiary hospitals in the Loudi, Shaoyang, and Xiangtan areas of China from January 21 to June 27, 2020, who were confirmed by RT-PCR to have SARS-CoV-2. The patients' clinical characteristics, laboratory results, treatments, and prognoses based on clinical classification were recorded. Poor outcome was defined as admission to an ICU, the use of mechanical ventilation, or death. Results: The patients were classified into four clinical groups based on disease severity, namely mild (10/218, 5%), moderate (146/218, 67%), severe (24/218, 11%), or critical (14/218, 6%); 24 (11%) asymptomatic cases were also included in the study. The most common symptoms were self-reported cough (162/218, 74%), fever (145/218, 67%), sputum production (99/218, 45%), and fatigue (77/218, 35%). Among the 218 patients, 192 (88%) received lopinavir/ritonavir and interferon-alpha inhalation, and 196 (90%) patients received traditional Chinese medicine. Among the severe and critical patients, 25 (11%) were admitted to an ICU with or without mechanical ventilation, and one patient died. The presence of diabetes [relative risk (RR), 3.0; 95% CI, 1.3-6.8; p = 0.007) or other comorbidities (RR, 5.9; 95% CI, 1.9-17.8; p = 0.002) was independently associated with poor outcome. To date, 20 (9%) patients have retested positive for SARS-CoV-2 RNA after recovering and being discharged. Conclusion: The majority of patients in this case series were clinically classified as having moderate COVID-19. Older patients tended to present with greater levels of clinical severity. The prognosis for patients who were elderly or had diabetes or other chronic comorbidities was relatively poor.

Gynura Segetum Related Hepatic Sinusoidal Obstruction Syndrome: A Liver Disease with High Mortality and Misdiagnosis Rate.

BACKGROUND AND AIM: Gynura segetum (Tusanqi or Jusanqi) is widely used in China as a herbal remedy, however, it has often been associated with hepatic sinusoidal obstruction syndrome (HSOS). Its extent in inducing hepatotoxicity is not sufficiently understood. Hence, we aimed to identify the characteristic features of Gynura segetum associated HSOS. METHODS: A total of 64 patients diagnosed with HSOS induced by gynura segetum were enrolled from eight Chinese tertiary care hospitals between 2008 and 2018. General information regarding diagnosis, disease history, suspected drug use, symptoms and signs, biochemical index, imaging data, liver histology, treatment methods, severity and prognosis were collected and analyzed. RESULTS: The mean age of the enrolled patients were 58.07±11.44 years. Male patients accounted for 64.1% of HSOS patients. The median latency period was 75 days. The number of patients with a definite diagnosis from the eight hospitals was 5 (7.81%), with a misdiagnosis rate of 92.18%. Hepatomegaly, splenomegaly, ascites and lower limbs edema were present in 89.1%, 76.6%, 81.3% and 43.8% of the patients, respectively. The imaging characteristic changes were liver parenchyma echo thickening, uneven density, and hepatic vein stenosis and occlusion. Liver biopsies had characteristic pathological changes. Except for ALT and D-Dimer, liver function and coagulation index at admission and before discharge were not significantly different (p>0.05). The 6-month mortality rate was 77.55%, with upper-gastrointestinal bleeding being the leading cause of death (42.11%). The second leading cause of death was a secondary infection (36.84%), while the third was hepatorenal syndrome (21.05%). CONCLUSION: Gynura segetum related HSOS often presents as progressive hepatic congestion, portal hypertension and liver failure, and has a high mortality and misdiagnosis rate.

The miR-383-LDHA axis regulates cell proliferation, invasion and glycolysis in hepatocellular cancer.

OBJECTIVES: To explore the correlation between expression patterns and functions of miR-383 and LDHA in hepatocellular cancer (HCC). MATERIALS AND METHODS: We detected the expression of miR-383 and LDHA in 30 HCC tissues and their matched adjacent normal tissues using qRT-PCR. Then we performed MTT assay, foci formation assay, transwell migration assay, glucose uptake assay and lactate production assay to explore the function of miR-383 in cell proliferation, invasion and glycolysis in HCC cell lines. Luciferase reporter assay was used to explore whether LDHA was a target gene of miR-383. Western blot and qRT-PCR were used to further confirm LDHA was targeted by miR-383. Then the above functional experiments were repeated to see whether the function of LDHA could be inhibited by miR-383. RESULTS: The results of qRT-PCR showed that miR-383 was down-regulated in HCC tissues compared with their matched adjacent normal tissues. Functional experiments showed that overexpression of miR-383 significantly suppressed cell proliferation, invasion and glycolysis. Luciferase reporter assay showed LDHA was a target gene of miR-383 and expression of LDHA was inversely correlated with that of miR-383 in HCC. Besides, increased cell proliferation, invasion and glycolysis triggered by LDHA could be inhibited by overexpression of miR-383 in HCC cell lines. CONCLUSION: Our study proved that miR-383 is down-regulated in HCC and acts as a tumor suppressor through targeting LDHA. Targeting the miR-383-LDHA axis might be a promising strategy in HCC treatment.