Background and Aim
Therapeutic duration of nucleos(t)ide analogues for chronic hepatitis B (CHB) is not indefinite in many parts of the world. Viral reactivation is common off therapy, but the risk ...of subsequent clinical outcome remains unclear and unpredictable. We aimed to quantify the incidence of and explore the predictors for clinical flare following virological relapse in CHB patients who discontinue entecavir therapy.
Methods
This multicenter cohort study prospectively monitored 133 CHB patients who were HBeAg‐negative and viral DNA‐undetectable when discontinuing entecavir after at least 3 years on therapy. Following virological relapse (viral DNA >2,000 IU/mL) that occurred in 92 patients, the incidences of subsequent clinical flare and persistent (unremittent for 3 months) or severe hepatitis (with jaundice or coagulopathy) were determined, and risk factors were explored. Patients did not resume antiviral therapy until occurrence of persistent or severe hepatitis.
Results
The cumulative incidence of clinical hepatitis 2 years after virological relapse was 61.0% (95% confidence interval CI, 49.9–72.3%) and that of persistent or severe hepatitis was 53.0% (95% CI, 40.9–66.2%). Serum viral load at the virological relapse was associated with both clinical hepatitis (adjusted hazard ratio HR, 1.31 per log IU/mL; 95% CI, 1.07–1.60) and persistent or severe hepatitis (adjusted HR, 1.63 per log IU/mL; 95% CI, 1.27–2.10), after adjustment for serum aminotransferase and alfa‐fetoprotein levels in the multivariate analysis. Viral DNA >100 000 IU/mL predicted a nearly inevitable occurrence of clinical flare (P < 0.0001).
Conclusions
A high viral load at the virological relapse predicts subsequent clinical hepatitis in CHB patients who discontinue entecavir.
Research has demonstrated that some tumor cells can transform into drug-tolerant persisters (DTPs), which serve as a reservoir for the recurrence of the disease. The persister state in cancer cells ...arises due to temporary molecular reprogramming, and exploring the genetic composition and microenvironment during the development of head and neck squamous cell carcinoma (HNSCC) can enhance our comprehension of the types of cell death that HNSCC, thus identifying potential targets for innovative therapies. This project investigated lipid-metabolism-driven ferroptosis and its role in drug resistance and DTP generation in HNSCC.
High levels of FSP1 were discovered in the tissues of patients who experienced relapse after cisplatin treatment. RNA sequencing indicated that a series of genes related to lipid metabolism were also highly expressed in tissues from these patients. Consistent results were obtained in primary DTP cells isolated from patients who experienced relapse. The Cancer Genome Atlas database confirmed this finding. This revealed that the activation of drug resistance in cancer cells is influenced by FSP1, intracellular iron homeostasis, and lipid metabolism. The regulatory roles of ferroptosis suppressor protein 1 (FSP1) in HNSCC metabolic regulation were investigated.
We generated human oral squamous cell carcinoma DTP cells (HNSCC cell line) to cisplatin and observed higher expression of FSP1 and lipid-metabolism-related targets
. The shFSP1 blockade attenuated HNSCC-DTP cell stemness and downregulated tumor invasion and the metastatic rate. We found that cisplatin induced FSP1/ACSL4 axis expression in HNSC-DTPC cells. Finally, we evaluated the HNSCC CSC-inhibitory functions of iFSP1 (a metabolic drug and ferroptosis inducer) used for neo-adjuvant chemotherapy; this was achieved by inducing ferroptosis in a patient-derived xenograft mouse model.
The present findings elucidate the link between iron homeostasis, ferroptosis, and cancer metabolism in HNSCC-DTP generation and acquisition of chemoresistance. The findings may serve as a suitable model for cancer treatment testing and prediction of precision treatment outcomes. In conclusion, this study provides clinically oriented platforms for evaluating metabolism-modulating drugs (FSP1 inhibitors) and new drug candidates of drug resistance and ferroptotic biomarkers.
The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in ...Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.
Background. Most literature regarding lung abscess focuses on anaerobic bacterial lung abscess, and aerobic gram-negative bacillary infection is less frequently discussed. This study was conducted to ...investigate the bacteriology of community-acquired lung abscess and to improve the empirical therapeutic strategy for adults with community-acquired lung abscess. Methods. We reviewed and analyzed data on 90 consecutive adult cases of bacteriologically confirmed community-acquired lung abscess treated during 1995–2003 at a tertiary university hospital in Taiwan. Results. We found that a high proportion (21%) of cases of lung abscess were due to Klebsiella pneumoniae infection, which differs from the findings of previous studies. Lung abscess due to K. pneumoniae was associated with underlying diabetes mellitus (odds ratio OR, 4.3; 95% confidence interval CI, 1.0–18.4; P = .039) and negatively correlated with a time from onset of symptoms to diagnosis of >30 days (OR, 0.2; 95% CI, 0.1–0.7; P = .008). A higher percentage of patients with K. pneumoniae lung abscess had concomitant bacteremia (OR, 9.4; 95% CI, 1.1–81.9; P = .032), delayed defervesence (OR, 9.2; 95% CI, 1.8–47.8; P = .004), and multiple cavities noted on radiographs (OR, 11.0; 95% CI, 1.3–94.9; P = .015), compared with patients with anaerobic bacterial lung abscess. The rate of nonsusceptibility to clindamycin and penicillin among anaerobes and Streptococcus milleri group isolates increased. Conclusion. K. pneumoniae has become a more common cause of lung abscess than before, and a high proportion of anaerobes and S. milleri strains have become resistant to penicillin and clindamycin. A β-lactam/β-lactamase inhibitor or second- or third-generation cephalosporin with clindamycin or metronidazole is suggested as empirical antibiotic therapy for community-acquired lung abscess.
OBJECTIVE—Vascular endothelial growth factor (VEGF), a major mediator of angiogenesis, exerts its proangiogenic action by binding to VEGFR2 (VEGF receptor 2), the activity of which is further ...modulated by VEGFR2 coreceptors such as neuropilins. However, whether VEGFR2 is regulated by additional coreceptors is not clear. To investigate whether SCUBE2 (signal peptide-CUB-EGF domain-containing protein 2), a peripheral membrane protein expressed in vascular endothelial cells (ECs) known to bind other signaling receptors, functions as a VEGFR2 coreceptor and to verify the role of SCUBE2 in the VEGF-induced angiogenesis.
APPROACH AND RESULTS—SCUBE2 lentiviral overexpression in human ECs increased and short hairpin RNA knockdown inhibited VEGF-induced EC growth and capillary-like network formation on Matrigel. Like VEGF, endothelial SCUBE2 was upregulated by hypoxia-inducible factor-1α at both mRNA and protein levels. EC-specific Scube2 knockout mice were not defective in vascular development but showed impaired VEGF-induced neovascularization in implanted Matrigel plugs and recovery of blood flow after hind-limb ischemia. Coimmunoprecipitation and ligand-binding assays showed that SCUBE2 forms a complex with VEGF and VEGFR2, thus acting as a coreceptor to facilitate VEGF binding and augment VEGFR2 signal activity. SCUBE2 knockdown or genetic knockout suppressed and its overexpression promoted the VEGF-induced activation of downstream proangiogenic and proliferating signals, including VEGFR2 phosphorylation and mitogen-activated protein kinase or AKT activation.
CONCLUSIONS—Endothelial SCUBE2 may be a novel coreceptor for VEGFR2 and potentiate VEGF-induced signaling in adult angiogenesis.
Gastroesophageal reflux disease (GERD) has become a major health problem globally, affecting patients' health-related quality of life (HRQOL). Barrett's esophagus (BE) is a precancerous lesion ...associated with GERD. BE patients might not only suffer from HRQOL losses by GERD but also face psychological distress due to the increased risk of developing cancer. However, the majority of patients in Asia have shorter BE segment which is different from the West. This study aimed to determine whether the HRQOL in BE patients were worse than in healthy referents in Taiwan.
Patients who received referral esophagogastroduodenoscopy for various symptoms were evaluated for the existence of BE. Lesions were judged as endoscopically suspected esophageal metaplasia (ESEM) if they showed morphological resemblances to BE by endoscopy. The diagnosis of BE was confirmed by histology with intestinal metaplasia or gastric metaplasia based on the Montreal definition. The World Health Organization Quality of Life (WHOQOL-BREF) was administered to BE patients before treatment. For each BE patient, we selected 2 age-, sex-, educational background and municipality-matched healthy referents, sampled by simple randomization method from a national survey in Taiwan. Multiple linear regression models were constructed to control the potential confounders.
A total of 84 patients diagnosed with BE were enrolled as BE group and then compared with 168 healthy referents. The BE group had significantly lower WHOQOL-BREF scores than those of healthy referents in the physical domain (P < 0.05) but higher scores in the environment domain (P < 0.05). In the physical domain, the BE group had significantly lower scores in various facets, including pain, discomfort, sleep and rest and dependence on medications or treatments. There was no significant difference in social and psychological domains between the BE group and healthy referents.
BE patients suffer from poor sleep and rest and high dependence on medications, which significantly reduce their quality of life. Individual facets of each domain warrants a better clinical healthcare to improve quality of life of BE patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Identification of disease severity remains a challenge in the management of non-alcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18), is a recently developed non-invasive biomarker for NASH. We ...aimed to assess the performance of CK18 in disease severity prediction among Taiwanese NASH patients.
A total of 76 biopsy-proven NASH patients (54 males, age = 41.0 ± 13.5 years) were consecutively recruited. The optimal cutoff values of CK18 for each stage of fibrosis were correlated with their histopathological manifestations.
There were 23 (30.3%) patients of Metavir fibrosis stage 0 (F0), 32 (42.1%) patients of F1, 14 (18.4%) patients of F2, and 7 (9.2%) patients of F3-4, respectively. The CK18 levels among those patients of F0, F1, F2, F3-4 were 86.7 ± 75.6 U/L, 122.4 ± 123.8 U/L, 160.7 ± 120.4 U/L, and 507.3 ± 343 U/L, respectively (trend for P<0.001). The adjusted optimal cutoff value for F2 prediction was 312.5 U/L, yielding the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the accuracy of 96.4%, 28.6%, 77.9%, 75%, and 77.6%, respectively (P = 0.009). For the prediction of advanced fibrosis (F3-4), the adjusted optimal cutoff value was 374.5 U/L, yielding the sensitivity, specificity, PPV, NPV, and the accuracy of 97.1%, 54.1%, 95.7%, 66.7%, and 77.6%, respectively (P = 0.003). Among those patients without hyperuricemia, the PPV, NPV, and accuracy of CK18 reached 100%, 95.8%, and 96%, respectively (P<0.001).
CK18 combined with uric acid measurement is a promising non-invasive biomarker for prediction of disease severity in NASH patients.
ClinicalTrials.gov NCT01068444.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As time evolved, traditional Chinese medicine (TCM) became integrated into the global medical system as complementary treatments. Some essential TCM herbs started to play a limited role in clinical ...practices because of Western medication development. For example, Fuzi (Aconiti Lateralis Radix Praeparata) is a toxic but indispensable TCM herb. Fuzi was mainly used in poor circulation and life-threatening conditions by history records. However, with various Western medication options for treating critical conditions currently, how is Fuzi used clinically and its indications in modern TCM are unclear. This study aimed to evaluate Fuzi and Fuzi-based formulas in modern clinical practices using artificial intelligence and data mining methods.
This nationwide descriptive study with market basket analysis used a cohort selected from the Taiwan National Health Insurance database that contained one million national representatives between 2003 and 2010 used for our analysis. Descriptive statistics were performed to demonstrate the modern clinical indications of Fuzi. Market basket analysis was calculated by the Apriori algorithm to discover the association rules between Fuzi and other TCM herbs.
A total of 104,281 patients using 405,837 prescriptions of Fuzi and Fuzi-based formulas were identified. TCM doctors were found to use Fuzi in pulmonary (21.5%), gastrointestinal (17.3%), and rheumatologic (11.0%) diseases, but not commonly in cardiovascular diseases (7.4%). Long-term users of Fuzi and Fuzi-based formulas often had the following comorbidities diagnosed by Western doctors: osteoarthritis (31.0%), peptic ulcers (29.5%), hypertension (19.9%), and COPD (19.7%). Patients also used concurrent medications such as H2-receptor antagonists, nonsteroidal anti-inflammatory drugs, β-blockers, calcium channel blockers, and aspirin. Through market basket analysis, for the first time, we noticed many practical Fuzi-related herbal pairs such as Fuzi-Hsihsin (Asari Radix et Rhizoma)-Dahuang (Rhei Radix et Rhizoma) for neurologic diseases and headache.
For the first time, big data analysis was applied to uncover the modern clinical indications of Fuzi in addition to traditional use. We provided necessary evidence on the scientific use of Fuzi in current TCM practices, and the Fuzi-related herbal pairs discovered in this study are helpful to the development of new botanical drugs.
COVID-19 has exposed major weaknesses in the healthcare settings. The surge in COVID-19 cases increases the demands of health care, endangers vulnerable patients, and threats occupational safety. In ...contrast to a hospital outbreak of SARS leading to a whole hospital quarantined, at least 54 hospital outbreaks following a COVID-19 surge in the community were controlled by strengthened infection prevention and control measures for preventing transmission from community to hospitals as well as within hospitals. Access control measures include establishing triage, epidemic clinics, and outdoor quarantine stations. Visitor access restriction is applied to inpatients to limit the number of visitors. Health monitoring and surveillance is applied to healthcare personnel, including self-reporting travel declaration, temperature, predefined symptoms, and test results. Isolation of the confirmed cases during the contagious period and quarantine of the close contacts during the incubation period are critical for containment. The target populations and frequency of SARS-CoV-2 PCR and rapid antigen testing depend on the level of transmission. Case investigation and contact tracing should be comprehensive to identify the close contacts to prevent further transmission. These facility-based infection prevention and control strategies help reduce hospital transmission of SARS-CoV-2 to a minimum in Taiwan.
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