Alteration of adeS Contributes to Tigecycline Resistance and Collateral Sensitivity to Sulbactam in Acinetobacter baumannii.

The treatment of extensively drug-resistant (XDR) A. baumannii has emerged as a major problem. Tigecycline (TGC) and sulbactam (SUL) are both effective antibiotics against XDR A. baumannii. Here, we investigated the in-host evolution and mechanism of collateral sensitivity (CS) phenomenon in development of tigecycline resistance accompanied by a concomitant increase of sulbactam susceptibility. A total of four XDR A. baumannii strains were sequentially isolated from the same patient suffering from bacteremia. Core-genome multilocus sequence typing separated all the strains into two clusters. Comparative analysis of isolate pair 1 revealed that multiplication of blaOXA-23 within Tn2006 on the chromosome contributed to the change in the antimicrobial susceptibility phenotype of isolate pair 1. Additionally, we observed the emergence of CS to sulbactam in isolate pair 2, as demonstrated by an 8-fold increase in the TGC MIC with a simultaneous 4-fold decrease in the SUL MIC. Compared to the parental strain Ab-3557, YZM-0406 showed partial deletion in the two-component system sensor adeS. Reconstruction of the adeS mutant in Ab-3557 in situ suggested that TGC resistance and CS to SUL were mainly caused by the mutation of adeS. Overall, our study reported a novel CS combination of TGC and SUL in A. baumannii and further revealed a mechanism of CS attributed to the mutation of adeS. This study provides a valuable foundation for developing effective regimens and sequential combinations of tigecycline and sulbactam against XDR A. baumannii. IMPORTANCE Collateral sensitivity (CS) has become an increasingly common evolutionary trade-off during adaptive bacterial evolution. Here, we report a novel combination of tigecycline (TGC) resistance and CS to sulbactam (SUL) in A. baumannii. TGC and SUL are both effective antibiotics against XDR A. baumannii, and it is essential to reveal the mechanism of CS between TGC and SUL. In our study, the partial deletion of adeS, a two-component system sensor, was confirmed to be the key factor contributing to this CS phenomenon. This study provides a valuable foundation for developing effective regimens and sequential combinations of tigecycline and sulbactam against XDR A. baumannii.

Predictors of Psychological Distress among Patients with Colorectal Cancer-Related Enterostomy: A Cross-sectional Study.

OBJECTIVE: To identify variables that may predict psychological distress in patients with an enterostomy. METHODS: Investigators recruited 77 patients with a stoma from a stoma clinic according to the inclusion criteria. Patients' psychological distress was assessed with the Distress Thermometer (DT) tool, and their personality type was determined by the Eysenck Personality Questionnaire. Researchers also collected demographic and disease-related data. Predictive values were estimated using multiple regression analyses. RESULTS: The mean DT score of all patients was 5.94 (SD, 1.81), and approximately 85.7% consistently suffered from psychological distress. Being unmarried and having peristomal complications were associated with higher psychological distress, whereas having a monthly income 5,000 ¥ or more was associated with lower levels of distress. Moreover, patients with a melancholic personality type tended to have higher DT scores, which could act as a strong independent predictor for psychological distress. CONCLUSIONS: The majority of patients with a stoma endured moderate to severe psychological distress during follow-up care. Exploring the related factors that predict the levels of psychological distress could enable clinicians to identify at-risk patients as early as possible and thus provide optimal care for improving patients' quality of life.

Mutation Spectrum of EGFR From 21,324 Chinese Patients With Non-Small Cell Lung Cancer (NSCLC) Successfully Tested by Multiple Methods in a CAP-Accredited Laboratory.

Genotyping epidermal growth factor receptor (EGFR) gene in patients with advanced non-small cell lung cancers (NSCLC) is essential for identifying those patients who may benefit from targeted therapies. Systemically evaluating EGFR mutation detection rates of different methods currently used in clinical setting will provide valuable information to clinicians and laboratory scientists who take care of NSCLC patients. This study retrospectively reviewed the EGFR data obtained in our laboratory in last 10 years. A total of 21,324 NSCLC cases successfully underwent EGFR genotyping for clinical therapeutic purpose, including 5,244 cases tested by Sanger sequencing, 13,329 cases tested by real-time PCR, and 2,751 tested by next-generation sequencing (NGS). The average EGFR mutation rate was 45.1%, with 40.3% identified by Sanger sequencing, 46.5% by real-time PCR and 47.5% by NGS. Of these cases with EGFR mutations identified, 93.3% of them harbored a single EGFR mutation (92.1% with 19del or L858R, and 7.9% with uncommon mutations) and 6.7% harbored complex EGFR mutations. Of the 72 distinct EGFR variants identified in this study, 15 of them (single or complex EGFR mutations) were newly identified in NSCLC. For these cases with EGFR mutations tested by NGS, 65.3% of them also carried tumor-related variants in some non-EGFR genes and about one third of them were considered candidates of targeted drugs. NGS method showed advantages over Sanger sequencing and real-time PCR not only by providing the highest mutation detection rate of EGFR but also by identifying actionable non-EGFR mutations with targeted drugs in clinical setting.

Parallel Analyses of Somatic Mutations in Plasma Circulating Tumor DNA (ctDNA) and Matched Tumor Tissues in Early-Stage Breast Cancer.

PURPOSE: Early detection and intervention can decrease the mortality of breast cancer significantly. Assessments of genetic/genomic variants in circulating tumor DNA (ctDNA) have generated great enthusiasm for their potential application as clinically actionable biomarkers in the management of early-stage breast cancer.Experimental Design: In this study, 861 serial plasma and matched tissue specimens from 102 patients with early-stage breast cancer who need chemotherapy and 50 individuals with benign breast tumors were deeply sequenced via next-generation sequencing (NGS) techniques using large gene panels. RESULTS: Cancer tissues in this cohort of patients showed profound intratumor heterogeneities (ITHGs) that were properly reflected by ctDNA testing. Integrating the ctDNA detection rate of 74.2% in this cohort with the corresponding predictive results based on Breast Imaging Reporting and Data System classification (BI-RADS) could increase the positive predictive value up to 92% and potentially dramatically reduce surgical overtreatment. Patients with positive ctDNA after surgery showed a higher percentage of lymph node metastasis, indicating potential recurrence and remote metastasis. The ctDNA-positive rates were significantly decreased after chemotherapy in basal-like and Her2+ tumor subtypes, but were persistent despite chemotherapy in luminal type. The tumor mutation burden in blood (bTMB) assessed on the basis of ctDNA testing was positively correlated with the TMB in tumor tissues (tTMB), providing a candidate biomarker warranting further study of its potentials used for precise immunotherapy in cancer. CONCLUSIONS: These data showed that ctDNA evaluation is a feasible, sensitive, and specific biomarker for diagnosis and differential diagnosis of patients with early-stage breast cancer who need chemotherapy.

Pustulibacterium marinum gen. nov., sp. nov., a member of the family Flavobacteriaceae isolated from the Bashi Channel.

A Gram-reaction-negative, non-spore-forming, gliding, non-translucent, colourless or yellow, aerobic and elevated-colony-forming strain, designated E403(T), was isolated from the Bashi Channel and subjected to a polyphasic taxonomic study. Strain E403(T) could grow in the presence of 0.3-8 % (w/v) NaCl, at 16-43 °C and at pH 6-9, and grew optimally at 28 °C, pH 8, in natural seawater medium. The respiratory quinones were MK-6 and MK-7. The major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G, summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), iso-C15 : 0 3-OH and C16 : 0. The DNA G+C content of strain E403(T) was 37.9 mol%. Phylogenetic analyses based on 16S rRNA gene sequences of members of the family Flavobacteriaceae showed that strain E403(T) formed a distinct evolutionary lineage within the stable cluster containing type strains Zhouia amylolytica HN-171(T) (92.2 % similarity) and Joostella marina En5(T) (92.4 % similarity). In addition to the large 16S rRNA gene sequence differences, E403(T) can also be distinguished from the reference type strains J. marina En5(T) and Sinomicrobium oceani SCSIO 03483(T) by several phenotypic characteristics and chemotaxonomic properties. On the basis of phenotypic, chemotaxonomic and phylogenetic properties, strain E403(T) is suggested to represent a novel species of a new genus in the family Flavobacteriaceae, for which the name Pustulibacterium marinum gen. nov., sp. nov. is proposed. The type strain is E403(T) (= CCTCC AB2012862(T) = CGMCC 1.12333(T) = KCTC 32192(T)).