Search

Introduction: Acute-on-chronic liver failure (ACLF) patients are susceptible to invasive fungal infections. We evaluated the prognosis and antifungal options in ACLF patients with invasive pulmonary aspergillosis (IPA). Methods: ACLF patients with IPA from 15 hospitals were retrospectively screened from 2011 to 2018, and 383 ACLF patients without lung infections were included from a prospective cohort (NCT02457637). Demographic, laboratory, clinical data, and 28-day outcomes were documented in the two cohorts. Results: ACLF patients with probable IPA (n= 145) had greater 28-day mortality (33.6% vs. 15.7%, p< 0.001) than those without (n= 383). The respiratory failure-associated 28-day mortality was greater in ACLF patients with IPA than in those without before (17.1% vs. 0.3%, p< 0.001) and after (16.0% vs. 0.0%, p< 0.001) propensity score matching in 116 pairs. IPA patients with lung injury had greater 28-day all-cause mortality (66.5% vs. 24.2%, p< 0.001) and IPA-associated mortality (45.8% vs. 8.1%, p< 0.001) than patients without lung injury (PaO2/FiO2 ≥ 400 mmHg). Antifungal therapy was prescribed to 139 of 145 patients, and 102 patients were treated with voriconazole alone (n= 59) or sequential/combined therapy (n= 43) with varying loading doses (100–800 mg) and daily maintenance doses (0–800 mg). A proposed optimal voriconazole regimen (loading dose, 200 mg twice daily; daily maintenance dose, 100 mg) achieved comparable short-term survival and optimal trough drug concentrations (1–5 μg/mL) on therapeutic drug monitoring in 26 patients. Conclusion: Presence of IPA increases the short-term mortality of ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients.

Introduction: Spontaneous fungal ascites infection is a rare but devastating complication of cirrhosis. We aimed to analyse the clinical features, short-term mortality, and treatment of spontaneous fungal ascites infection in patients with cirrhosis. Methods: We retrospectively studied ten patients with cirrhosis and spontaneous fungal ascites infections, and the clinical characteristics and outcomes were obtained. Result: The patients’ mean age was 64 ± 13 years, and seven of the ten patients were men. Cirrhosis was primarily caused by infection with the hepatitis B virus. Candida albicanswas the most frequently isolated fungus isolated from the ascites fluid. Three of the ten patients fulfilled the criteria of acute-on-chronic liver failure (ACLF) at baseline, and three of the remaining seven patients developed ACLF during hospitalisation. Of the ten patients, six had acute kidney injury (AKI), and six died within 28 days. Three patients did not receive antifungal treatment during hospitalisation because they died undiagnosed because of delays in the reporting of laboratory results. Conclusion: Patients with spontaneous fungal ascites infection had high incidence of AKI and 28-day mortality. Fungal cultures of ascitic fluid from patients with cirrhosis should be recommended to ensure optimal clinical management, especially in patients with severe liver disease and who received inadequate empirical antibacterial therapy. Hence, future studies should focus on the early diagnosis of fungal infection in patients with cirrhosis.

During cancer progression, tumorigenic and immune signals are spread through circulating molecules, such as cell-free DNA (cfDNA) and cell-free RNA (cfRNA) in the blood. So far, they have not been comprehensively investigated in gastrointestinal cancers. Here, we profile 4 categories of cell-free omics data from patients with colorectal cancer and patients with stomach adenocarcinoma and then assay 15 types of genomic, epigenomic, and transcriptomic variations. We find that multi-omics data are more appropriate for detection of cancer genes compared with single-omics data. In particular, cfRNAs are more sensitive and informative than cfDNAs in terms of detection rate, enriched functional pathways, etc. Moreover, we identify several peripheral immune signatures that are suppressed in patients with cancer. Specifically, we establish a γδ-T cell score and a cancer-associated-fibroblast (CAF) score, providing insights into clinical statuses like cancer stage and survival. Overall, we reveal a cell-free multi-molecular landscape that is useful for blood monitoring in personalized cancer treatment.

The relationship between anemia and the outcome of patients with cirrhosis is not completely clear. Therefore, we performed this large-scale epidemiological study to investigate the prevalence and severity of anemia in patients with cirrhosis and acute decompensation or liver injury and how anemia impacts short-term and long-term outcomes.

Gilbert’s syndrome and hereditary hemochromatosis predominantly affect Caucasians with a low incidence in Asians. Here we report the case of a 16-year-old Chinese boy, who was admitted with hepatalgia, jaundice, hyperpigmentation, and splenomegaly to our hospital. After excluding chronic hepatitis, autoimmune disorders, and alcohol or drug injury, genetic analyses of the patient and his parents revealed simultaneous manifestations of Gilbert’s syndrome and hereditary hemochromatosis, though his parents did not develop related symptoms. The presented case indicates that diagnoses of Gilbert’s syndrome and hereditary hemochromatosis should be taken into consideration when chronic hepatitis is suspected without a clear etiology.

Spontaneous mutations introduce uncertainty into coronavirus disease 2019 (COVID-19) control procedures and vaccine development. Here, we perform a spatiotemporal analysis on intra-host single-nucleotide variants (iSNVs) in 402 clinical samples from 170 affected individuals, which reveals an increase in genetic diversity over time after symptom onset in individuals. Nonsynonymous mutations are overrepresented in the pool of iSNVs but underrepresented at the single-nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated in the host (positive selection), and these substitutions tend to be unfixed as SNPs in the population (negative selection). Dynamic iSNV changes in subpopulations with different gender, age, illness severity, and viral shedding time displayed a varied fitness selection process among populations. Our study highlights that iSNVs provide a mutational pool shaping the rapid global evolution of the virus.

Influenza is a serious public health problem that endangers the health of the global human population. Traditional Chinese medicine (TCM) is rich in theory and practical experience regarding the treatment of influenza, and TCM treatments have shown good curative effects, but there is a dearth of standardized clinical guidance. It is necessary to formulate a clinical practice guide based on evidence-based medicine. To this end, the Specialty Committee of Emergency, China Association of Chinese Medicine (Beijing, China) organized a team of clinical experts, methodological experts, and other multidisciplinary experts to develop a guideline with integrated research methods in the first place of TCM. This guide includes 23 recommendations. The prescription section contains 16 recommendations, including 5 recommendations for mild cases, 5 recommendations for severe cases, 3 recommendations for critical cases, and 4 recommendations for the recovery period; the portion covering proprietary Chinese medicines forms a total of 7 recommendations. This guide aims to provide the best evidence for clinicians and related practitioners to make decisions about influenza diagnosis and treatment in Chinese medicine.