We profiled the serological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein and spike (S) glycoprotein. The majority of the patients developed robust antibody responses between 17 and 23 days after illness onset. Delayed, but stronger, antibody responses were observed in critical patients.
Pseudomonas aeruginosa is a biofilm-forming opportunistic pathogen which causes chronic infections in immunocompromised patients and leads to high mortality rate. It is identified as a common coinfecting pathogen in COVID-19 patients causing exacerbation of illness. In our hospital, P. aeruginosa is one of the top coinfecting bacteria identified among COVID-19 patients. We collected a strong biofilm-forming P. aeruginosa strain displaying small colony variant morphology from a severe COVID-19 patient. Genomic and transcriptomic sequencing analyses were performed with phenotypic validation to investigate its adaptation in SARS-CoV-2 infected environment. Genomic characterization predicted specific genomic islands highly associated with virulence, transcriptional regulation, and DNA restriction-modification systems. Epigenetic analysis revealed a specific N6-methyl adenine (m6A) methylating pattern including methylation of alginate, flagellar and quorum sensing associated genes. Differential gene expression analysis indicated that this isolate formed excessive biofilm by reducing flagellar formation (7.4 to 1,624.1 folds) and overproducing extracellular matrix components including CdrA (4.4 folds), alginate (5.2 to 29.1 folds) and Pel (4.8–5.5 folds). In summary, we demonstrated that P. aeuginosa clinical isolates with novel epigenetic markers could form excessive biofilm, which might enhance its antibiotic resistance and in vivo colonization in COVID-19 patients.
Background: Co-infections, secondary bacterial or fungal infections, are important risk factors for poor outcomes in viral infections. The prevalence of co-infection and secondary infection in patients infected with SARS-CoV-2 is not well understood. Aims: To investigate the role of co-infections and secondary infections in disease severity of hospitalized individuals with COVID-19. Materials and Methods: A retrospective study was carried out between 11 January 2020 and 1 March 2020 among 408 laboratory confirmed COVID-19 patients in China. These patients were divided into three groups based on disease severity: mild or moderate, severe, or critically ill. Microbiological pathogens in blood, urine, and respiratory tract specimens were detected by the combination of culture, serology, polymerase chain reaction, and metagenomic next-generation sequencing (mNGS). Results: The median age of participants was 48 years (IQR 34-60 years). Fifty-two patients (12.7%) had at least one additional pathogen, 8.1% were co-infected, and 5.1% had a secondary infection. There were 13 Mycoplasma pneumoniae cases, 8Haemophilus influenzae cases, 8 respiratory viruses, and 3 Streptococcus pneumoniae cases, primarily detected in mild and moderate COVID-19 patients. Hospitalacquired infection pathogens were more common in critically ill patients. Compared to those without additional pathogens, patients with co-infections and/or secondary infections were more likely to receive antibiotics (p < 0.001) and have elevated levels of d-dimer (p = 0.0012), interleukin-6 (p = 0.0027), and procalcitonin (p = 0.0002).The performance of conventional culture was comparable with that of mNGS in diagnosis of secondary infections. Conclusion: Co-infections and secondary infections existed in hospitalized COVID-19 patients and were relevant to the disease severity. Screening of common respiratory pathogens and hospital infection control should be strengthened.
This open-label, randomized phase II trial was performed to compare the efficacy and safety of nimotuzumab plus S-1 and cisplatin (NCS) versus S-1 and cisplatin (CS) alone in patients with untreated unresectable or metastatic gastric cancer in the first-line setting.Eligible participants were randomly assigned (1:1) to receive either NCS or CS. The treatment consisted of 3-week cycles of twice-daily S-1 40 mg/m2 (on days 1–14) and intravenous cisplatin 30 mg/m2 (on days 1, 2), with or without weekly nimotuzumab (200 mg/m2). The primary endpoint was objective response rate (ORR). The second endpoint included progression-free survival (PFS), overall survival (OS), safety and association between efficacy and tumor epidermal growth factor receptor (EGFR) expression.Between October, 2009, and February, 2012, we enrolled 62 patients in Cancer Hospital Chinese Academy of Medical Sciences (CAMS). The ORR for 31 patients allocated NCS was 54.8% compared with 58.1% for 31 patients who were allocated to receive CS alone (P = 0.798). Median PFS for patients in CS arm was significantly improved than that in NCS arm [7.2 months vs. 4.8 months HR = 2.136 (95% CI 1.193–3.826), P = 0.011]. There was also a trend toward better overall survival for patients in CS arm compared with NCS arm [14.3 months vs. 10.2 months; HR = 1.776 (95% CI 0.972–3.246), P = 0.062]. In the EGFR 2+/3+ subgroup, adding nimotuzumab also failed to show additional benefit than chemotherapy alone. Both groups were well tolerated. Less than 10% of patients in both arms developed grade 3/4 toxicity.Combination of nimotuzumab and S-1-cisplatin provided no additional benefit than chemotherapy alone in the first-line treatment of unresectable or metastatic gastric cancer.
Purpose This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib. Methods It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12 mg/day, Day1–14, 3 weeks per cycle). The primary endpoint was 12-week progression-free survival (PFS) rate. Relationship between the series plasma cytokine level and the efficacy of anlotinib was analyzed. Results Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% [95% confidence interval (CI); 59.8%–91.5%] and median time to progression (TTP) was 5.9 months (95% CI 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI 48.7%–86.6%) and 4.6 months (95% CI 2.7–10.0), respectively. The median TTP on patients with a baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significantly longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). Conclusion Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for the efficacy of anlotinib.
PurposeWe conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with nab-paclitaxel and S-1 followed by S-1 maintenance therapy.MethodsNab-paclitaxel was administered intravenously on days 1 and 8 at 120 mg/m2. S-1 at 120 mg/day (for surface area ≥ 1.5 m2), 100 mg/day (for surface area between 1.25–1.5 m2), and 80 mg/day (for surface area < 1.25 m2) were given two times daily on days 1–14 every 3 weeks. Patients who achieved response and stable disease after 6 cycles were given S-1 maintenance treatment in the same schedule until disease progression or unacceptable toxicity developed. The primary endpoint was objective response rate (ORR), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Between 01/2015 and 07/2017, 32 patients were enrolled.ResultsThe ORR in the intention-to-treat (ITT) population (N = 32) was 53.1%, and the DCR was 87.5%. In the 30 evaluable patients, the ORR and DCR were 56.7 and 93.3%, respectively. The median follow-up time was 18 (range 12–36) months, the median PFS was 6.2 (range 4.4–8) months, and the median OS was 13.6 (range 8.7–18.5) months. The incidence of grade 3/4 neutropenia was 27.6%. Other grade 3 adverse events included 1 (3.1%) hand–foot syndrome, 1 (3.1%) rash and 2 (6.3%) diarrheas.ConclusionsNab-paclitaxel and S-1 regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer.
Background COVID-19 pneumonia has caused huge impact on the health of infected patients and associated with high morbidity and mortality. Shift in the lung microbial ecology upon such viral infection often worsens the disease and increases host susceptibility to superinfections. Bacterial superinfection contributes to the aggravation of COVID-19 and poses a great challenge to clinical treatments. An in-depth investigation on superinfecting bacteria in COVID-19 patients might facilitate understanding of lung microenvironment post virus infections and superinfection mechanism. Results We analyzed the adaptation of two pairs of P. aeruginosa strains with the same MLST type isolated from two critical COVID-19 patients by combining sequencing analysis and phenotypic assays. Both P. aeruginosa strains were found to turn on alginate biosynthesis and attenuate type VI secretion system (T6SS) during short-term colonization in the COVID-19 patients, which results in excessive biofilm formation and virulence reduction-two distinct markers for chronic infections. The macrophage cytotoxicity test and intracellular reactive oxygen species measurement confirmed that the adapted P. aeruginosa strains reduced their virulence towards host cells and are better to escape from host immune clearance than their ancestors. Conclusion Our study suggests that SARS-CoV-2 infection can create a lung environment that allow rapid adaptive evolution of bacterial pathogens with genetic traits suitable for chronic infections.
A retrospective comparison of S-1 plus oxaliplatin and capecitabine plus oxaliplatin as adjuvant chemotherapies for stage II and III gastric cancer after D2 resection in Chinese patients. SOX has similar survival benefits to XELOX and is well-tolerated in Chinese patients with GC following D2 gastrectomy. There was no significant difference in peritoneal metastasis rates in these two groups. Metastatic lymph node ratio was an independent prognostic factor for OS.The clinical data were collected after informed consent and approval of the Ethical Committee Abstract Background: Capecitabine plus oxaliplatin (XELOX) as adjuvant therapy for gastric cancer (GC) reduces cancer recurrence and improves survival. S-1 plus oxaliplatin (SOX) is well-tolerated and effective against advanced GC, and also be used widely in adjuvant treatment. However, data comparing SOX and XELOX as adjuvant treatments are lacking.Method: Data on treatment modalities, adverse events, recurrence and metastasis were collected from 180 patients with stage II and III GC, who received SOX or XELOX after D2 gastrectomy between January 2012 and December 2015, and analyzed retrospectively. The primary endpoint was 3-year disease-free survival (DFS) rate. Results:Median follow was 52.9 months; 3-year DFS rate and overall survival (OS) rate were 75.2% and 67.6% (P = 0.359) and 81.2% and 83.3% (P = 0.77) in the SOX and XELOX groups, respectively. There was no significant difference in peritoneal metastasis rates in the SOX and XELOX groups (8.6% vs 15%, respectively; P = 0.232). Compound recurrent disease was associated with significantly shorter OS. Multivariate analysis identified metastatic lymph node ratio (LNR) as an independent prognostic factor for OS (P = 0.036; hazard ratio = 2.875; 95% confidence interval, 1.069-7.729); the LNR ≥17% group had inferior 3-year OS rate to the LNR <17% group (P = 0.001). The incidence of grades 3 and 4 adverse events was similar in both groups; however, grade ≥2 hand-foot syndrome was significantly less frequent in the SOX group (P = 0.01).Conclusion: SOX has similar survival benefits to XELOX and is well-tolerated in Chinese patients with GC following D2 gastrectomy. K E Y W O R D Sadjuvant chemotherapy, gastric cancer, SOX, XELOX
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.