Development of a machine learning-based radiomics signature for estimating breast cancer TME phenotypes and predicting anti-PD-1/PD-L1 immunotherapy response.

BACKGROUNDS: Since breast cancer patients respond diversely to immunotherapy, there is an urgent need to explore novel biomarkers to precisely predict clinical responses and enhance therapeutic efficacy. The purpose of our present research was to construct and independently validate a biomarker of tumor microenvironment (TME) phenotypes via a machine learning-based radiomics way. The interrelationship between the biomarker, TME phenotypes and recipients' clinical response was also revealed. METHODS: In this retrospective multi-cohort investigation, five separate cohorts of breast cancer patients were recruited to measure breast cancer TME phenotypes via a radiomics signature, which was constructed and validated by integrating RNA-seq data with DCE-MRI images for predicting immunotherapy response. Initially, we constructed TME phenotypes using RNA-seq of 1089 breast cancer patients in the TCGA database. Then, parallel DCE-MRI images and RNA-seq of 94 breast cancer patients obtained from TCIA were applied to develop a radiomics-based TME phenotypes signature using random forest in machine learning. The repeatability of the radiomics signature was then validated in an internal validation set. Two additional independent external validation sets were analyzed to reassess this signature. The Immune phenotype cohort (n = 158) was divided based on CD8 cell infiltration into immune-inflamed and immune-desert phenotypes; these data were utilized to examine the relationship between the immune phenotypes and this signature. Finally, we utilized an Immunotherapy-treated cohort with 77 cases who received anti-PD-1/PD-L1 treatment to evaluate the predictive efficiency of this signature in terms of clinical outcomes. RESULTS: The TME phenotypes of breast cancer were separated into two heterogeneous clusters: Cluster A, an "immune-inflamed" cluster, containing substantial innate and adaptive immune cell infiltration, and Cluster B, an "immune-desert" cluster, with modest TME cell infiltration. We constructed a radiomics signature for the TME phenotypes ([AUC] = 0.855; 95% CI 0.777-0.932; p < 0.05) and verified it in an internal validation set (0.844; 0.606-1; p < 0.05). In the known immune phenotypes cohort, the signature can identify either immune-inflamed or immune-desert tumor (0.814; 0.717-0.911; p < 0.05). In the Immunotherapy-treated cohort, patients with objective response had higher baseline radiomics scores than those with stable or progressing disease (p < 0.05); moreover, the radiomics signature achieved an AUC of 0.784 (0.643-0.926; p < 0.05) for predicting immunotherapy response. CONCLUSIONS: Our imaging biomarker, a practicable radiomics signature, is beneficial for predicting the TME phenotypes and clinical response in anti-PD-1/PD-L1-treated breast cancer patients. It is particularly effective in identifying the "immune-desert" phenotype and may aid in its transformation into an "immune-inflamed" phenotype.

Using the non-distortion IVIM to reduce the need for contrast agents in nasopharyngeal MRI.

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) who undergo longitudinal follow-up contrast-enhanced MRI are at risk of developing gadolinium deposition in their neural tissue, which may potentially harm them. Therefore, for these patients, a non-contrast-enhanced method is potentially beneficial as an alternative approach to predict enhancement in T1-weighted imaging (CE-T1WI). The traditional intravoxel incoherent motion (IVIM) is one of the non-contrast-enhanced methods; however, the severe distortion and signal loss limit its application in patients with NPC. The present study aimed to investigate whether non-distortion IVIM could reduce the need of CE-T1WI in the follow-up of patients with NPC. METHODS: The patients with NPC underwent Turbo Spin-echo MVXD diffusion-weighted imaging-based IVIM (non-distortion IVIM) from November 2021 to May 2022. Firstly, thirty patients with NPC were underwent both non-distortion IVIM and traditional IVIM. The distortion rate (DR) of the non-distortion IVIM was compared with the traditional IVIM. Then, twenty-one NPC patients with tumors (areas >50mm2) were included and correlation coefficient analysis was used to assess the relationship between their non-distortion IVIM and CE-T1WI. Linear regression analysis was performed to determine whether non-distortion IVIM predictors could predict CE-T1WI. RESULTS: The correlation was observed between the parameter f of the non-distortion IVIM and the enhancement ratio of CE-T1WI (r = 0.543, P = 0.011). Moreover, the linear regression analysis revealed that f was an independent IVIM predictor of CE-T1WI in patients with NPC (P = 0.011). The DR of the non-distortion IVIM was significantly smaller than that of the traditional IVIM (0.12 ± 0.05 vs 0.48 ± 0.16, P < 0.001). CONCLUSIONS: In patients with NPC, non-distortion IVIM showed potential clinical benefits to reduce the need for contrast agents, and it can independently predict the enhancement ratio.

Value of mammographic microcalcifications and MRI-enhanced lesions in the evaluation of residual disease after neoadjuvant therapy for breast cancer.

Background: Microcalcifications persist even if a patient with breast cancer achieves pathologic complete response (pCR) as confirmed by surgery after neoadjuvant treatment (NAT). In practice, surgeons tend to remove all the microcalcifications. This study aimed to explore the correlation between changes in the extent of microcalcification after NAT and pathological tumor response and compare the accuracy of mammography (MG) and magnetic resonance imaging (MRI) in predicting the size of residual tumors. Methods: This was a retrospective study which included a consecutive series of patients in Guangdong Provincial People's Hospital. Between January 2010 and January 2020, 127 patients with breast cancer and Breast Imaging Reporting and Data System (BI-RADS) 4-5 microcalcifications were included in this study. The maximum diameter of the microcalcifications on MG and lesion enhancement on MRI pre- and post-NAT were measured. The correlations between the changes in residual microcalcifications on MG and pCR were analyzed. Intraclass correlation coefficients (ICCs) were computed between the extent of the residual microcalcifications, residual enhancement, and residual tumor size. Results: There were no statistically significant differences in the changes in microcalcifications after NAT according to the RECIST criteria on MRI (P=0.09) and Miller-Payne grade (P=0.14). MRI showed a higher agreement than did residual microcalcifications on MG in predicting residual tumor size (ICC: 0.771 vs. 0.097). Conclusions: MRI is more accurate for evaluating residual tumor size in breast cancer. In our study, the extent of microcalcifications on MG after NAT had nearly no correlation with the pathological size of the residual tumor. Therefore, residual tumors with microcalcifications may not necessarily be a contraindication to breast-conserving surgery.

Artificial intelligence-assisted analysis for tumor-immune interaction within the invasive margin of colorectal cancer.

BACKGROUND: In colorectal cancer (CRC), both tumor invasion and immunological analysis at the tumor invasive margin (IM) are significantly associated with patient prognosis, but have traditionally been reported independently. We propose a new scoring system, the TGP-I score, to assess the association and interactions between tumor growth pattern (TGP) and tumor infiltrating lymphocytes at the IM and to predict its prognostic validity for CRC patient stratification. MATERIALS AND METHODS: The types of TGP were assessed in hematoxylin and eosin-stained whole-slide images. The CD3+ T-cells density at the IM was automatically quantified on immunohistochemical-stained slides using a deep learning method. A discovery (N = 347) and a validation (N = 132) cohorts were used to evaluate the prognostic value of the TGP-I score for overall survival. RESULTS: The TGP-I score3 (trichotomy) was an independent prognostic factor, with higher TGP-I score3 associated with worse prognosis in the discovery (unadjusted hazard ratio [HR] for high vs. low 3.62, 95% confidence interval [CI] 2.22-5.90; p < 0.001) and validation cohort (unadjusted HR for high vs. low 5.79, 95% CI 1.84-18.20; p = 0.003). The relative contribution of each parameter to predicting survival was analyzed. The TGP-I score3 had similar importance compared to tumor-node-metastasis staging (31.2% vs. 32.9%) and was stronger than other clinical parameters. CONCLUSIONS: This automated workflow and the proposed TGP-I score could further provide accurate prognostic stratification and have potential value for supporting the clinical decision-making of stage I-III CRC patients.Key messagesA new scoring system, the TGP-I score, was proposed to assess the association and interactions of TGP and TILs at the tumor invasive margin.TGP-I score could be an independent predictor of prognosis for CRC patients, with higher scores being associated with worse survival.TGP-I score had similar importance compared to tumor-node-metastasis staging and was stronger than other clinical parameters.

Necrosis score as a prognostic factor in stage I-III colorectal cancer: a retrospective multicenter study.

BACKGROUND: Tumor necrosis results from failure to meet the requirement for rapid proliferation of tumor, related to unfavorable prognosis in colorectal cancer (CRC). However, previous studies used traditional microscopes to evaluate necrosis on slides, lacking a simultaneous phase and panoramic view for assessment. Therefore, we proposed a whole-slide images (WSIs)-based method to develop a necrosis score and validated its prognostic value in multicenter cohorts. METHODS: Necrosis score was defined as the proportion of necrosis in the tumor area, semi-quantitatively classified into 3-level score groups by the cut-off of 10% and 30% on HE-stained WSIs. 768 patients from two centers were enrolled in this study, divided into a discovery (N = 445) and a validation (N = 323) cohort. The prognostic value of necrosis score was evaluated by Kaplan-Meier curves and the Cox model. RESULT: Necrosis score was associated with overall survival, with hazard ratio for high vs. low in discovery and validation cohorts being 2.62 (95% confidence interval 1.59-4.32) and 2.51 (1.39-4.52), respectively. The 3-year disease free survival rates of necrosis-low, middle, and high were 83.6%, 80.2%, and 59.8% in discovery cohort, and 86.5%, 84.2%, and 66.5% in validation cohort. In necrosis middle plus high subgroup, there was a trend but no significant difference in overall survival between surgery alone and adjuvant chemotherapy group in stage II CRC (P = .075). CONCLUSION: As a stable prognostic factor, high-level necrosis evaluated by the proposed method on WSIs was associated with unfavorable outcomes. Additionally, adjuvant chemotherapy provide survival benefits for patients with high necrosis in stage II CRC.

L-distance ratio: a new distance ratio-based evaluation method for the diagnosis of cirrhosis using enhanced computed tomography.

Background: Early detection of liver cirrhosis is of great significance to the formulation of treatment plans and improving prognosis. Computed tomography (CT) is commonly used in the assessment of patients with chronic liver disease. In this study, we proposed a new distance ratio method for accurate diagnosis of cirrhosis using CT images. Methods: This was a retrospective study of a consecutive series of patients in Guangdong Provincial People's Hospital. Sixty-two patients with pathologically diagnosed cirrhosis but whose morphologic changes were insufficient to diagnose cirrhosis were included in the cirrhosis group. Those who were pathologically confirmed to be free of cirrhosis and fibrosis and without a history of chronic hepatic were classified as the control group. A total of 124 patients underwent abdominal dynamic enhanced CT. Both the L-distance ratio-the ratio of the distance from the right portal vein bifurcation point to the anterior and posterior edges of the liver-and the caudate-right lobe ratio were measured by two independent radiologists. Intraclass correlation coefficients (ICCs) were used to assess the agreement between the radiologists. Binary logistic regression was performed for univariate analysis, and the odds ratio (OR) was also calculated. The discrimination ability of the two methods was evaluated by the area under the receiver operating characteristic curve (AUC). Results: For both the L-distance ratio and the caudate-right lobe ratio, high agreement was observed between the two radiologists, although the ICC value of the L-distance ratio was slightly higher than that of the caudate-right lobe ratio (0.916 vs. 0.907). Binary logistic regression suggested that higher ratios were correlated with cirrhosis [the L-distance ratio, high vs. low OR =4.41, 95% confidence interval (CI): 2.08-9.36, P<0.001; the caudate-right lobe ratio, high vs. low OR =2.19, 95% CI: 1.07-4.49, P=0.031]. The AUCs of the L-distance ratio and the caudate-right lobe ratio were 0.823 (95% CI: 0.752-0.894) and 0.663 (95% CI: 0.569-0.757), respectively. Conclusions: The L-distance ratio method proposed in this paper is more simple, accurate, and reliable than the caudate-right lobe ratio method in the diagnosis of cirrhosis.

Artificial intelligence for quantifying immune infiltrates interacting with stroma in colorectal cancer.

BACKGROUND: We proposed an artificial intelligence-based immune index, Deep-immune score, quantifying the infiltration of immune cells interacting with the tumor stroma in hematoxylin and eosin-stained whole-slide images of colorectal cancer. METHODS: A total of 1010 colorectal cancer patients from three centers were enrolled in this retrospective study, divided into a primary (N = 544) and a validation cohort (N = 466). We proposed the Deep-immune score, which reflected both tumor stroma proportion and the infiltration of immune cells in the stroma region. We further analyzed the correlation between the score and CD3+ T cells density in the stroma region using immunohistochemistry-stained whole-slide images. Survival analysis was performed using the Cox proportional hazard model, and the endpoint of the event was the overall survival. RESULT: Patients were classified into 4-level score groups (score 1-4). A high Deep-immune score was associated with a high level of CD3+ T cells infiltration in the stroma region. In the primary cohort, survival analysis showed a significant difference in 5-year survival rates between score 4 and score 1 groups: 87.4% vs. 58.2% (Hazard ratio for score 4 vs. score 1 0.27, 95% confidence interval 0.15-0.48, P < 0.001). Similar trends were observed in the validation cohort (89.8% vs. 67.0%; 0.31, 0.15-0.62, < 0.001). Stratified analysis showed that the Deep-immune score could distinguish high-risk and low-risk patients in stage II colorectal cancer (P = 0.018). CONCLUSION: The proposed Deep-immune score quantified by artificial intelligence can reflect the immune status of patients with colorectal cancer and is associate with favorable survival. This digital pathology-based finding might advocate change in risk stratification and consequent precision medicine.

Artificial intelligence for quantifying Crohn's-like lymphoid reaction and tumor-infiltrating lymphocytes in colorectal cancer.

Crohn's-like lymphoid reaction (CLR) and tumor-infiltrating lymphocytes (TILs) are crucial for the host antitumor immune response. We proposed an artificial intelligence (AI)-based model to quantify the density of TILs and CLR in immunohistochemical (IHC)-stained whole-slide images (WSIs) and further constructed the CLR-I (immune) score, a tissue level- and cell level-based immune factor, to predict the overall survival (OS) of patients with colorectal cancer (CRC). The TILs score and CLR score were obtained according to the related density. And the CLR-I score was calculated by summing two scores. The development (Hospital 1, N = 370) and validation (Hospital 2 & 3, N = 144) cohorts were used to evaluate the prognostic value of the CLR-I score. The C-index and integrated area under the curve were used to assess the discrimination ability. A higher CLR-I score was associated with a better prognosis, which was identified by multivariable analysis in the development (hazard ratio for score 3 vs score 0 = 0.22, 95% confidence interval 0.12-0.40, P < 0.001) and validation cohort (0.21, 0.05-0.78, P = 0.020). The AI-based CLR-I score outperforms the single predictor in predicting OS which is objective and more prone to be deployed in clinical practice.

Preoperative prediction of intra-tumoral tertiary lymphoid structures based on CT in hepatocellular cancer.

PURPOSE: Intra-tumoral tertiary lymphoid structures (TLSs) are associated with a favorable prognosis for patients with hepatocellular carcinoma (HCC). We aimed to identify image features related to TLSs and develop a nomogram for preoperative noninvasive prediction of intra-tumoral TLSs. METHODS: This retrospective study enrolled patients with HCC who underwent contrast-enhanced computed tomography before surgery between January 2014 and September 2020. Two radiologists retrospectively and independently reviewed the CT imaging features, and interobserver agreement was assessed. Univariable and multivariable logistic regression analyses were applied to investigate clinical laboratory data and imaging features related to TLSs. A regression-based predictive model and nomogram were constructed using the identified predictors. Nomogram diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curves, and validated using 5-fold cross-validation. RESULTS: Ninety-three of the 142 HCCs were TLS + HCCs. Multivariable analyses identified intratumor arteries (odds ratio [OR]: 0.23; 95% confidence interval [CI]: 0.07-0.63; p = 0.007), intratumor hemorrhage (OR: 0.08; 95% CI: 0.01-0.50; p = 0.012), positive HBsAg or HCVAB status (OR: 4.52; 95% CI: 1.65-13.29; p = 0.004), platelet count (≥186.5 × 109 /L, OR: 0.38; 95% CI: 0.16-0.86; p = 0.022), and aspartate transaminase level (≥33.2 IU/l, OR: 0.24; 95% CI: 0.09-0.59; p = 0.003) as independent predictors of intra-tumoral TLSs. AUC of the regression-based model was 0.79 (95% CI:0.72-0.86) and average AUC at 5-fold cross-validation was 0.75 (95% CI: 0.71-0.80). CONCLUSIONS: CT-based nomogram is promising for preoperative prediction of intra-tumoral TLS in HCC.

Spleen Radiomics Signature: A Potential Biomarker for Prediction of Early and Late Recurrences of Hepatocellular Carcinoma After Resection.

OBJECTIVES: To explore the usefulness of spleen radiomics features based on contrast-enhanced computed tomography (CECT) in predicting early and late recurrences of hepatocellular carcinoma (HCC) patients after curative resection. METHODS: This retrospective study included 237 HCC patients who underwent CECT and curative resection between January 2006 to January 2016. Radiomic features were extracted from CECT images, and then the spleen radiomics signatures and the tumor radiomics signatures were built. Cox regression analysis was performed to identify the independent risk factors of early and late recurrences. Then, multiple models were built to predict the recurrence-free survival of HCC after resection, and the incremental value of the radiomics signature to the clinicopathologic model was assessed and validated. Kaplan-Meier survival analysis was used to assess the association of the models with RFS. RESULTS: The spleen radiomics signature was independent risk factor of early recurrence of HCC. The mixed model that integrated microvascular invasion, tumor radiomics signature and spleen radiomics signature for the prediction of early recurrence achieved the highest C-index of 0.780 (95% CI: 0.728,0.831) in the primary cohort and 0.776 (95% CI: 0.716,0.836) in the validation cohort, and presented better predictive performance than clinicopathological model and combined model. In the analysis of late recurrence, the spleen radiomics signature was the only prognostic factor associated with late recurrence of HCC. CONCLUSIONS: The identified spleen radiomics signatures are prognostic factors of both early and late recurrences of HCC patients after surgery and improve the predictive performance of model for early recurrence.

A totally implantable venous access port associated with bloodstream infection caused by Mycobacterium fortuitum: A case report.

RATIONALE: Rapidly growing mycobacteria (RGM) are well-known causative agents of human infections, particularly in immunocompromised hosts. However, Mycobacterium fortuitum, a predominant organism, in catheter-associated infections, has rarely been documented in totally implantable venous access port (TVIAP)-associated bloodstream infections. PATIENT CONCERNS: A 25-year-old woman with breast cancer presented to hospital with repeated fever for several days. The patient first refused to remove the TVIAP in her body, and had a relapse of M. fortuitum bacteraemia four months later. DIAGNOSES: Bacteria isolated from patient's blood and TVIAP were identified as M. fortuitum by Matrix-assisted laser desorption/ionization-time of flight spectrometry and bacterial 16s rDNA sequencing. The patient was diagnosed as a TVIAP-associated bloodstream infection. INTERVENTIONS: The TVIAP was eventually surgically removed, and M. fortuitum was found to have localized on the tip of the catheter. The patient was treated by anti-infection therapy. OUTCOMES: The patient was treated with 4 weeks of intravenous amikacin and levofloxacin followed by 4 weeks of oral levofloxacin. No episodes of fever occurred during the follow-up to date. LESSONS: RGM infections remain a challenging issue for TIVAPs. Accurate species identification, timely intravascular catheter removal and appropriate antibiotic therapy are recommended to ensure successful outcomes.

Genetic variant in visfatin gene promoter contributes to reduced risk of hepatocellular carcinoma in a Chinese population.

Knowledge on the role of gene variants in the visfatin promoter region in the hepatitis B virus (HBV)-related liver diseases is limited. In this study, we genotyped two potentially functional single nucleotide polymorphisms (SNPs) in the visfatin promoter region, -1535C>T (rs61330082) and -3187G>A (rs11977021), in 120 HBV-related chronic hepatitis B (CHB) patients, 140 HBV-related liver cirrhosis (HBV-LC) patients, 243 HBV-related hepatocellular carcinoma (HBV-HCC) patients, and 224 asymptomatic HBV carriers. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. The results showed subjects with a TT genotype of -1535C>T had a significantly decreased risk of HBV-HCC related to the CC and CC + CT genotypes (adjusted OR = 0.493, 95% CI = 0.313-0.778; OR = 0.535, 95% CI = 0.362-0.791, respectively). A lowered risk also appeared in the comparison between allele T and allele C (OR = 0.734, 95%, CI = 0.581-0.950). However, these associations existed only in people with Zhuang ethnicity, but not in people with Han ethnicity. There were no significant associations between -3187G>A polymorphisms and the risk of HBV-related liver diseases. Our results suggested that visfatin -1535C>T polymorphisms might be associated with decreased risk of HBV-HCC among the ethnic Zhuang population in Guangxi, China.

A 10 year surveillance for antimicrobial susceptibility of Escherichia coli and Klebsiella pneumoniae in community- and hospital-associated intra-abdominal infections in China.

The objective of this study was to investigate the susceptibility of hospital-associated (HA) and community-associated (CA) Escherichia coli and Klebsiella pneumoniae isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2011, the minimum inhibitory concentrations (MICs) of 12 antibiotics against 3074 E. coli and 1025 K. pneumoniae from 23 centres located in 16 cities were determined by the broth microdilution method. During the 10 year study period, ertapenem, imipenem, amikacin and piperacillin-tazobactam retained high and stable activity against E. coli and K. pneumoniae isolates regardless of whether their source was HA or CA and regardless of their extended-spectrum beta-lactamase (ESBL) production. However, the susceptibility of E. coli to cephalosporins and ampicillin-sulbactam decreased dramatically during the 10 years, especially for the CA isolates. Fluoroquinolones showed low activity against E. coli. During the whole study period, the ESBL rates for E. coli isolates from IAIs increased from 36.1 % in 2002-2003 to 68.1 % in 2010-2011 (P<0.001). Correspondingly, the ESBL rates in HA isolates increased from 52.2 % in 2002-2003 to 70.0 % in 2010-2011 (P = 0.001), and in CA isolates from 19.1 % in 2002-2003 to 61.6 % in 2010-2011 (P<0.001). The ESBL-positive rate in K. pneumoniae remained between 30.1 and 39.3 % of the total isolates with no significant change during the 10 years. In conclusion, carbapenems retained the highest susceptibility rates against HA and CA E. coli and K. pneumoniae. High prevalence of ESBL in HA E. coli and fast-growing resistance in CA E. coli severely limit the empirical use of the third- and fourth-generation cephalosporins in the therapy of IAIs.

Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: the 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART).

The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli (GNB) isolated from patients with intra-abdominal infections (IAIs) in China. From 2002 to 2009, minimum inhibitory concentrations of 14 antibiotics for 3420 aerobic and facultative GNB from up to eight hospitals in six cities were determined by the broth microdilution method. Enterobacteriaceae comprised 82.9% (2834/3420) of the total isolates, with Escherichia coli (49.2%) being the most commonly isolated species followed by Klebsiella pneumoniae (17.0%), Enterobacter cloacae (5.8%) and Citrobacter freundii (2.3%). Amongst the antimicrobial agents tested, the three carbapenems (ertapenem, imipenem and meropenem) were the most active agents against Enterobacteriaceae, with susceptibility rates of 96.1-99.6% (2002-2009), 98.2-100% (2002-2009) and 99.6-100% (2002-2004), respectively, followed by amikacin (86.8-95.1%) and piperacillin/tazobactam (84.5-94.3%). Susceptibility rates of all tested third- and fourth-generation cephalosporins against Enterobacteriaceae declined by nearly 30%, with susceptibility rates of 40.2%, 39.1%, 56.3% and 51.8% in 2009 for ceftriaxone, cefotaxime, ceftazidime and cefepime, respectively. The occurrence of extended-spectrum ß-lactamases increased rapidly, especially for E. coli (from 20.8% in 2002 to 64.9% in 2009). Susceptibility of E. coli to ciprofloxacin decreased from 57.6% in 2002 to 24.2% in 2009. The least active agent against Enterobacteriaceae was ampicillin/sulbactam (SAM) (25.3-44.3%). In conclusion, Enterobacteriaceae were the major pathogens causing IAIs, and carbapenems retained the highest susceptibility rates over the 8-year study period. Third- and fourth-generation cephalosporins, fluoroquinolones and SAM may not be ideal choices for empirical therapy of IAIs in China.

Comparison of exhaust emissions resulting from cold- and hot-start motorcycle driving modes.

This study investigated the emissions of criteria air pollutants (carbon monoxide [CO], hydrocarbons [HCs], and oxides of nitrogen [NOx]) from motorcycle exhaust at cold- and hot-start driving cycles on a chassis dynamometer. Seven four-stroke carburetors and two fuel-injection motorcycles were tested. As expected, the emission factors (g/km) of CO and HCs increased during cold-start driving. The ratio of emission factors (g/km) for cold- and hot-start driving cycles ranged from 1.1-1.5 (for CO) to 1.2-2.8 (for HCs). However, the difference of NOx emissions between the cold- and hot-start cycles was not pronounced. Further, the cold-/hot-start ratios of CO and HCs from 50-cm3 motorcycles were higher than those of 100- and 125-cm3 motorcycles; however, the carbon dioxide (CO2) emission was the lowest for the four-stroke motorcycles. High engine temperature and poor combustion efficiency of smaller cylinder-capacity motorcycles may contribute a significant amount of exhaust emission. Additionally, the fuel-base emission factor (g/L-fuel) ratios were low compared with the distance-base emission factor (g/km) in cold- and hot-start driving. This indicates that the effect of catalyst efficiency was greater than the effect of fuel combustion in the tested motorcycles. A comparison of emission ratios of motorcycles and passenger cars shows that the warm-up may be more important for cars, especially under low-temperature conditions. However, the motorcycle contributes a large proportion of CO and HC emissions in many Asian counties. The difference between cold- and hot-start emissions may affect inventory

Molecular evidence for spread of two major methicillin-resistant Staphylococcus aureus clones with a unique geographic distribution in Chinese hospitals.

Methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) is a serious problem worldwide. To investigate the molecular epidemiology of MRSA isolates in China, a total of 702 MRSA isolates collected from 18 teaching hospitals in 14 cities between 2005 and 2006 were characterized by antibiogram analysis, pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome mec (SCCmec) typing, and spa typing; and 102 isolates were selected for multilocus sequence typing (MLST). Overall, SCCmec type III was the most popular type and was found in 541 isolates (77.1%), followed by SCCmec type II (109/702; 15.5%). Twenty-four PFGE types were obtained among 395 isolates collected in 2005, and 18 spa types were obtained among 702 isolates. spa type t030, which corresponded to PFEG types A to E, constituted 52.0% (365/702) of all isolates, and isolates of this type were present in all 14 cities; spa type t037, which corresponded to PFGE types F and G, accounted for 25.5% (179/702) of all isolates, and isolates of this type were identified in 12 cities. The two spa genotypes belonged to sequence type 239 (ST239) and carried SCCmec type III. spa type t002, which included isolates of PFGE types L to T, made up 16.0% (112/702) of the isolates that belonged to ST5 and SCCmec type II, and isolates of this type were distributed in 12 cities. The distribution of spa types varied among the regions. spa type t002 was the most common in Dalian (53.4%) and Shenyang (44.4%); spa type t037 was predominant in Shanghai (74.8%), whereas spa type t030 was the most common in the other cities. Two isolates from Guangzhou that harbored SCCmec type IVa with ST59 and ST88 were identified as community-associated MRSA. The prevalence of the Panton-Valentine leukocidin gene was 2.3%. The data documented two major epidemic MRSA clones, ST239-MRSA-SCCmec type III and ST5-MRSA-SCCmec type II, with unique geographic distributions across China.

[Resistance study of community respiratory pathogens isolated in China from 2005 to 2007].

OBJECTIVE: To investigate the antimicrobial resistance of community respiratory pathogens isolated in China. METHODS: The strains of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. pyogenes were isolated from patients with community-acquired respiratory tract infections at 14 Chinese hospitals from 2005 to 2007. Etest and disk diffusion methods were used to survey the susceptibility of 14 antibiotics against these strains. These antibiotics included penicillin G, ampicillin, amoxicillin/clavulanic acid, cefaclor, cefprozil, ceftriaxone, cefepime, levofloxacin, gatifloxacin, ciprofloxacin, tetracycline, clindamycin, erythromycin and trimethoprim/sulfamethoxazole (SXT). RESULTS: A total of 1870 strains were collected including S. pneumoniae (n = 997), S. pyogenes (n = 176), H. influenzae (n = 499) and M. catarrhalis (n = 198). The 2005 - 2007 prevalence of penicillin-susceptible S. pneumoniae (PSSP) were 92.6%, 73.9%, 74.1% and penicillin-intermediate S. pneumoniae (PISP) 4.5%, 9.5%, 14.3% and penicillin-resistant S. pneumoniae (PRSP) 2.9%, 16.6%, 11.6% respectively. 36.9% of S. pneumoniae strains isolated from or= 92.9%. CONCLUSIONS: Antimicrobial resistance in S. pneumoniae is rising. The prevalence of PNSSP isolated from children < or = 6 years old is higher than other age groups. Amoxicillin-clavulanic acid, ceftriaxone, cefepime, gatifloxacin and levofloxacin remain highly active against common community respiratory pathogens.

[Surveillance of antimicrobial resistance among nosocomial gram-negative pathogens from 15 teaching hospitals in China in 2005].

OBJECTIVE: To investigate the antimicrobial resistance among the nosocomial gram-negative pathogens from 15 teaching hospitals located in different areas in China in 2005. METHODS: A total of 1927 non-repetitive nosocomial gram-negative pathogens were collected from 15 teaching hospitals in different areas in China and sent to the central lab for reidentification and susceptibility testing. The levels of minimal inhibitory concentration (MIC) of 18 antimicrobial agents were determined by agar dilution method. WHONET 5.4 software was used to analyze the data. RESULTS: The strains of Escherichia coli, Klebsiella pneumoniae, and Proteous mirabilis isolates that did not produce extended spectrum beta lactamases (ESBLs) showed high sensitivity to beta-lactams. The antibiotics with a susceptibility rates over 80% against the strains of Entorobacter cloacae, Enterobacter aerogene, Citrobacter spp, Serratia spp, and Proteous vulgaris producing AmpC enzyme included meropenem, imipenem, and piperacillin-tazobactam, and these 3 drugs showed a susceptibility rate of more than 80% against the ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae. Other antimicrobial agents showing a relatively high activity against Enterobacter spp, Citrobacter spp, Serratia spp and Proteous vulgaris included cefepime (67.3% - 100%), amikacin (67.3% - 95.2%), ceftazidime (52.9% - 100%) and cefoperazone-sulbactam (51.9% - 100%). The susceptibility rate of fluoroquinolones was 34.8% - 36.1% against non-ESBL-producing Escherichia coli and was 13.4% - 17.1% against ESBL-producing isolates. The most active agent against Pseudomonas aeruginosa was polymyxin B (95.6%). The agents with the activity rates of 70% - 80% included meropenem, imipenem, amikacin, and piperacillin-tazobactam. The antibiotic with a high susceptible rate against Acinetobacter baumannii was polymyxin B (98.3%), followed by imipenem (80.8%), meropenem (76.2%), and minocycline (67.4%). The susceptible rates of other agents were all below 60%. The agents with relatively high activity against Stenotrophomonas maltophilia included minocycline (85%), levofloxacin (82.5%), and trimethoprim-sulfamethoxazole (77.5%). The agents with a relatively high activity against Burkholderia cepacia included minocycline (77.2%) and meropenem (61.4%). CONCLUSION: Carbapenem, piperacillin-tazobactam, amikacin and cefepime remained relatively high activity against nosocomial Enterobacteriaceae, Non-fermenting pathogens have lower susceptibility to the antimicrobial agents than before.

bla(IMP-9) and its association with large plasmids carried by Pseudomonas aeruginosa isolates from the People's Republic of China.

A novel plasmid-mediated metallo-beta-lactamase (IMP-9) is described in seven isolates of Pseudomonas aeruginosa from Guangzhou, China, isolated in 2000. The gene was carried on a large (approximately 450-kb) IncP-2 conjugative plasmid. This is the first report of carriage of bla(IMP) genes on such large plasmids.

Multicenter antimicrobial susceptibility survey of gram-negative bacteria isolated from patients with community-acquired infections in the People's Republic of China.

A survey of 2,099 gram-negative bacilli from community infections at seven centers in the People's Republic of China is reported. The rates of resistance of 1,615 isolates of the family Enterobacteriaceae were as follows: 40.8% for ciprofloxacin, 32.2% for gentamicin, 0% for imipenem or ertapenem, and 14.7% for cefotaxime. The rates of extended-spectrum beta-lactamase production were 16% for Escherichia coli and 17% for Klebsiella.