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Tao Lu,1,* Longfeng Zhang,2,* Mingqiu Chen,3 Xiaobin Zheng,2 Kan Jiang,2 Xinlong Zheng,2 Chao Li,4 Weijin Xiao,4 Qian Miao,2 Shanshan Yang,2 Gen Lin2 1Department of Radiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 2Department of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 3Department of Thoracic Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 4Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gen LinDepartment of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of ChinaEmail fjzllg133@fjzlhospital.comBackground: Predictive markers for guidance and monitoring of immunotherapy in lung squamous cell carcinoma (LSCC) are an interesting topic but have yet to be fully explored. A primary characteristic of LSCC is tumor necrosis that results in extensive immune suppression in patients. We sought to assess whether tumor necrosis or cavity on baseline CT could effectively predict the efficacy of immune checkpoint inhibitors (ICIs) in advanced LSCC.Methods: Advanced LSCC cases undergoing pre-treatment chest CT imaging and receiving ICIs were retrospectively collected. All CT images were reviewed by an independent chest radiologist blinded to any previous diagnosis to confirm morphological alterations in necrosis or cavity. We performed Logistic regression and developed Cox proportional hazards models to assess the predictive performance of baseline necrosis or cavity characteristics in advanced LSCC. Survival estimates were observed using Kaplan–Meier curves.Results: Ninety-three patients were eligible for analysis, predominantly consisting of patients with ECOG performance status of 0 or 1 (97.8%), male patients (95.7%), and heavy smokers (92.5%). Intrapulmonic necrosis or cavity on CT scan was present in 52.7% of all patients. Generally, the objective response rate (ORR) in patients with necrosis or cavity to ICI treatment was significantly worse versus those without (30.6% vs 54.5%, p = 0.020), with the subgroup ORRs as follows: ICI monotherapy (necrosis vs non-necrosis: 10.0% vs 36.8%, p =0.047) and ICI combination therapy (44.8% vs 68.0%, p =0.088). Multivariable analysis identified intrapulmonic necrosis or cavity at baseline as a major risk factor for advanced LSCC (HR 4.042, 95% CI1.149– 10.908, p = 0.006). Multivariate Cox analysis showed that baseline necrosis or cavity and ICI monotherapy were unfavorable factors for progression-free survival (HR 1.729; 95% CI1.203– 2.484, p =0.003).Conclusion: LSCC patients with intrapulmonic cavity or necrosis on baseline CT scan may respond poorly to anti-PD-(L)1-treatment, monotherapy and combination therapy alike.Keywords: lung squamous cell carcinoma, immune-checkpoint inhibitor, predictive marker, necrosis, cavity

Methods Forty-four COVID-19 patients (severe/critical: N = 8, non-severe: N = 36) were examined by next generation sequencing (NGS) of nasopharyngeal test paper to observe the effect of novel coronavirus infection to the microbial composition in upper airway. Results In these nasopharyngeal test paper samples, 38 kinds of bacteria, 10 kinds of viruses except SARS-CoV-2, nine kinds of fungi and three kinds of atypical pathogens had been found. There was some difference in microbial composition in the upper airway between severe and non-severe cases. Summary These results are important for us to study the effect of SARS-CoV-2 on the local microbial composition of upper airway and prevent opportunistic infection in severe patients.

Background Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae are potentially life-threatening related to poorer outcomes. Colistin is considered one of the last-resort treatments against human infections caused by multidrug-resistant (MDR) Gram-negative bacteria. Therefore, emergence of strains from the blood that co-harboring mcr and carbapenem resistance genes were considered as a serious problem. Purpose In this study, two mcr-9-harboring MDR Enterobacter cloacae isolates BSI034 and BSI072 recovered from BSI patients were identified, one of which co-harbored mcr-9 and bla NDM-1. The genetic characteristics of the MDR plasmid needed to be clarified. Methods S1-PFGE and Southern blotting were conducted to determine the location of mcr-9. Whole-genome sequencing was performed to obtain the complete genome and plasmid sequences. The resistome and virulence genes of the strains, accompanied by the genetic characteristics of mcr-9- and bla NDM-1-harboring plasmids, were analyzed. Results Whole-genome sequencing showed that BSI034 harbored mcr-9-carrying IncHI2-type pBSI034-MCR9 and bla NDM-1-carrying IncX3-type pBSI034-NDM1. The 278,517 bp pBSI034-MCR9 carried mcr-9 along with the other 19 resistance genes. mcr-9 was flanked by IS903B (1057 bp) and IS26 (820 bp) in the same orientation. In addition to resistance genes, strain BSI034 also carried a chromosome-located Yersinia high-pathogenicity island, which harbored genes of yersiniabactin biosynthesis operon ybtSXQPAUTE, irp1/2, and fyuA. Conclusion We described the complete genome and mcr-9/bla NDM-1-co-harboring plasmid of E. cloacae from a BSI patient. Notable differences were observed within mosaic modules between pBSI034-MCR9 and other mcr-9-harboring plasmids due to extensive recombination via horizontal gene transfer.

Awareness of the management of coronavirus disease 2019 (COVID-19) and airway diseases can effectively help clinical physician during the coronavirus pandemic. Herein, we elucidated a COVID-19 case coexisting with severe asthma. Budesonide/glycopyrrolate/formoterol fumarate (BGF) was used as sequential medicine to systemic glucocorticoids for his persisted symptoms related to bronchospasms. Our case suggests patients with long-term airway diseases like asthma probably attribute their symptoms to COVID-19 instead of primary diseases, which make it more difficult in the symptom control. BGF is able to be an effective and convenient choice as sequential medicine to systemic glucocorticoids in some refractory asthmatic patients complicated with COVID-19.

Purpose: The discovery of the plasmid-mediated colistin resistance genes, mcr, revealed a mechanism of transmission of colistin resistance, which is a major, global public health concern especially among individuals infected with carbapenem-resistant Gram-negative bacteria. To monitor the spread and epidemiology of mcr genes, a convenient and reliable method to detect mcr genes in clinical isolates is needed, especially in the primary care institutions. This study aimed to establish a restriction endonuclease-based multiplex loop-mediated isothermal amplification (multi-LAMP) assay to detect mcr genes (mcr-1 to mcr-5) harbored by colistin-resistant bacteria. Methods: A triple-LAMP assay for mcr-1, mcr-3, and mcr-4 and a double-LAMP assay for mcr-2 and mcr-5 were established. The sensitivity and specificity of the LAMP reactions were determined via electrophoresis and visual detection. Results: The sensitivity of the LAMP assay was 10-fold greater than that of PCR, with high specificity among the screened primers. Specific mcr genes were distinguished in accordance with band numbers and the fragment length of the digested LAMP amplification products. Furthermore, the LAMP assay was confirmed as a rapid and reliable diagnostic technique upon application for clinical samples, and the results were consistent with those of conventional PCR assay. Conclusion: The multi-LAMP assay is a potentially promising method to detect mcr genes and will, if implemented, help prevent infections by drug-resistant bacteria in primary-care hospitals due to rapid and reliable surveillance. To our knowledge, this is the first study to report the application of LAMP to detect mcr-2 to mcr-5 genes and the first time that multi-LAMP has been applied to detect mcr genes.

Background As a result of the growing prevalence of the plasmid-mediated mobile colistin resistance gene mcr-1 among Gram-negative bacteria, the surveillance of mcr-1 has been globally applied. In our study, we aimed to shed light on the possibility of transmission of mcr-1-resistant isolates through market retail fruits. Methods and results Herein, 133 different fruit surface samples were collected and screened for the different MCR variants (mcr-1 to mcr-8) using PCR and confirmed with sequencing. We identify for the first time mcr-1-carrying Escherichia coli and Klebsiella pneumoniae from market retail fruits in Guangzhou, China. Minimum inhibitory concentrations were detected by the broth microdilution method. Liquid mating was performed to check the transferability of the mcr-1 gene. Pulsed field gel electrophoresis analysis of S1 nuclease-digested DNA and Southern blotting were performed to check the location of the mcr-1 gene. Then, whole-genome sequencing and in silico multilocus sequence typing analysis were performed. Conclusion We showed that E. coli GB110 can mediate the spreading of antibiotic resistance genes through the food chain, while K. pneumoniae GB015 was considered to be the progenitor of the most successful multidrug-resistant clone. Since fruits are usually consumed fresh, this may serve as a direct source of mcr-1-producing bacteria in humans that requires prompt surveillance and intervention to limit the spread of resistance.

Purpose The main objective of this study was to decipher the prevalence, antimicrobial resistance, major virulence genes and the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolated from different clinical sources in southern China. Materials and methods The present study was performed on 187 non-duplicate S. aureus clinical isolates collected from three tertiary hospitals in Guangdong Province, China, 2010-2016. Antimicrobial susceptibility testing was performed by the disk diffusion method and by measuring the minimum inhibitory concentration. Screening for resistance and virulence genes was performed. Clonal relatedness was determined using various molecular typing methods such as multilocus sequence typing, spa and staphylococcal chromosomal cassette mec (SCCmec) typing. Whole genome sequencing was performed for three selected isolates. Results Out of 187 isolates, 103 (55%) were identified as MRSA. The highest prevalence rate was found among the skin and soft tissue infection (SSTI) samples (58/103), followed by sputum samples (25/103), blood stream infection samples (15/103) and others (5/103). Antimicrobial susceptibility results revealed high resistance rates for erythromycin (64.1%), clindamycin (48.5%), gentamicin (36.9%) and ciprofloxacin (33.98%). All isolates were susceptible to vancomycin. Resistance genes and mutation detected were as follows: aac(6')-aph(2") (24.3%), dfrG (10.7%), rpoB (21.4%), cfr (0%), fexA (1.94%), gyrA (35.92%), gyrB (0.97%), grlA (20.4%), grlB (10.68%), ermA (21.4%), ermB (18.44%), ermC (21.4%) and lnuA (18.44%). Profiling of virulence genes revealed the following: sea (11.7%), seb (21.4%), sec (0.97%), sed (0.97%), hla (86.41%), hlb (17.48%), hlg (10.68%), hld (53.4%), Tsst-1 (3.9%) and pvl (27.2%). Clonal relatedness showed that ST239-SCCmecA III-t37 clone was the most prevalent clone. Conclusion Our study elucidated the prevalence, antibiotic resistance, pathogenicity and molecular characteristics of MRSA isolated from various clinical sources in Guangdong, China. We found that the infectious rate of MRSA was higher among SSTI than other sources. The most predominant genotype was ST239-SCCmecA III-t37 clone, indicating that ST239-t30 clone which was previously predominant had been replaced by a new clone.

In this report, we analyze the trends in antimicrobial resistance of

Colistin is increasingly used as an antibiotic of last resort for treating carbapenem-resistant Enterobacteriaceae. Mobile colistin resistance gene mcr-1 has been increasingly reported in Enterobacteriaceae around the world. Of particular concern is the spread of mcr-1 into carbapenemase-producing Enterobacteriaceae, which results in highly drug-resistant strains that are potentially untreatable. Notably, such mcr-1-carrying isolates harboring carbapenemase genes have been reported in animals and patients with infection. Here, we report an Escherichia coli strain carrying co-transferable mcr-1-harboring IncX4 and blaNDM-5-harboring IncX3 plasmids, which was recovered in the context of fecal colonization.

Haiyu Hong,1,* Fenghong Chen,2,* Xiaobin Zheng,3 Wei Liao,1 Zhenpeng Liao,1 Yujie Cao,2 Haixin He,1 Zhe Zhu,4,5 Yunping Fan1 1Department of Otolaryngology and Head Neck Surgery of 5th Hospital, Affiliated with Sun Yat-sen University, Zhuhai, 2Department of Otolaryngology and Head Neck Surgery of 1st Hospital, Affiliated with Sun Yat-sen University, Guangzhou, 3Department of Respiration of 5th Hospital, Affiliated with Sun Yat-sen University, Zhuhai, China; 4Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 5Sanford Consortium, Regenerative Medicine, University of California, San Diego, La Jolla, CA,USA *These authors contributed equally tothis work Objective: There is little evidence on the role of topical budesonide in reducing the frequency of adenoidectomy, although it was reported that topical budesonide can effectively ameliorate the symptoms of adenoid hypertrophy (AH). This study was aimed to investigate the possibility and safety of alternatives to adenoidectomy with a 12-week treatment with nasal budesonide. Materials and methods: One hundred patients with AH were randomized to receive either a double-blind budesonide (1 mg once daily) or placebo treatment for 2 weeks by transnasal nebulization. A further 12-week open study, budesonide spray (64 µg per nostril at bedtime) was administered to the treatment group. During the final 12 weeks of follow-up, the frequency of adenotonsillectomy, side effects, the degree of nasal obstruction, nasal discharge, and snoring were assessed. Results: Out of the 100 total enrolled patients, 92 children with AH completed the study. After the 2-week treatment with transnasal budesonide nebulization, the symptoms of AH significantly decreased compared to the control group. Responders (n=26) who had initially improved showed significantly decreased symptoms of AH, and the frequency of adenotonsillectomy during the follow-up (14 and 26 weeks) was compared with that of the control group and non-responders (n=21) who did not respond to the initial 2-week budesonide therapy. The 12-week nasal budesonide treatment did not suppress the growth rate of children’s height or cause other side effects. Conclusion: AH children who had improved after an initial 2-week budesonide therapy can achieve clinical improvements and decreased frequency of adenoidectomy following the therapy with a 12-week treatment with nasal budesonide. Keywords: adenoid hypertrophy, adenoidectomy, budesonide, frequency, treatment