Different classes of antibiotics exhibit disparate negative impacts on the therapeutic efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

It has been reported that antibiotics (ATBs) have adverse effect on the efficacy of treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Since different classes of ATBs have different antibacterial spectrum, we aimed to study whether all ATBs had similar or different negative effects on the clinical outcomes of ICIs in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who received ICIs were included in this retrospective study and grouped by the class of ATBs they had used around the ICIs treatment time. The overall survival (OS) and the progression free survival (PFS) of patients among these groups were compared using Kaplan-Meier method and Cox proportional hazards model. A total of 148 eligible patients were enrolled, and 80 patients used ATBs. The results indicated that quinolones had no significant negative consequence on the clinical outcomes, while ß-lactams significantly shortened the OS and PFS of patients. Furthermore, patients exposed to the combination of ß-lactams and quinolones suffered the worst OS and PFS. Moreover, the subgroup analysis of ß-lactams revealed that only penicillins, but not carbapenems and cephalosporins, markedly reduced both OS and PFS. In addition to the class of ATBs used, the time frame of ATBs used also affected the clinical outcomes of ICIs therapy. Patients receiving ATBs within 60 days prior to and 30 days after the initiation of ICI treatment had significantly shorter OS and PFS compared with those who did not use ATBs. This study demonstrated that different classes of ATBs had disparate negative impacts on the clinical outcomes, and the use of ß-lactams, especially penicillins, should be avoided in advanced NSCLC patients who are receiving or scheduled to receive ICIs within 60 days.

Trends and Outcomes of Sentinel Lymph Node Biopsy in Early-stage Vulvar Squamous Cell Carcinoma: A Population-based Study.

Purpose: To compare trends and outcomes between lymphadenectomy and sentinel lymph node biopsy (SLNB) in node-negative early-stage vulvar squamous cell carcinoma (SCC) using a population-based cancer registry. Methods: Patients with vulvar SCC registered on the Surveillance, Epidemiology, and End Results program between 2003 and 2013 were identified. Statistical analysis was performed using Cox regression proportional hazards to calculate hazard ratio (HR) and 95% confidence interval (CI). A 1:1 propensity score matching (PSM) method was performed to minimize selection bias. Results: A total of 1475 patients were identified, including 1346 (91.3%) who received lymphadenectomy and 129 (8.7%) who underwent SLNB. The proportion of patients receiving SLNB increased between 2008 and 2013 compared with the years 2003-2007 (13.9% vs. 3.7%, p < 0.001). Five-year cause-specific survival (CSS) in patients who received lymphadenectomy and SLNB was 91.8% and 92.9%, respectively (p = 0.912), and 5-year overall survival (OS) was 77.5% and 82.5%, respectively (p = 0.403). SLNB was not associated with an decrease in CSS (HR 1.024, 95% CI 0.474-2.213, p = 0.952) or OS (HR 0.874, 95% CI 0.541-1.410, p = 0.581) in univariate and multivariate analyses. A total of 115 pairs were selected by PSM and survival analysis also showed comparable CSS (p = 0.481) and OS (p = 0.545) between lymphadenectomy and SLNB. Conclusions: There is an increasing trend toward SLNB in the treatment of patients with node-negative early-stage vulvar SCC, and survival is comparable between lymphadenectomy and SLNB.

Survival in signet ring cell carcinoma varies based on primary tumor location: a Surveillance, Epidemiology, and End Results database analysis.

BACKGROUND: The aim of this study was to investigate the survival of patients with signet ring cell carcinoma (SRCC) based on primary tumor location. METHODS: Patient data were obtained from the Surveillance, Epidemiology, and End Results database (1988-2012) with ≥200 cases per tumor location. Cox regression analysis was used to investigate prognostic factors of cause-specific survival (CSS). RESULTS: We identified 24,171 patients. Of the patients, 63.4% had gastric SRCC, followed by colon (18.2%), esophageal (5.0%), rectal (3.5%), lung (3.1%), pancreatic (1.8%), breast (1.5%), bladder (1.3%), small intestine (1.1%), and gallbladder SRCC (1.0%). The 5-year CSS was 22.1%, 69.0%, 33.2%, 28.1%, 24.8%, 16.1%, 13.6%, 12.6%, 11.0%, 6.4% in patients with gastric, breast, colon, rectum, bladder, small intestine, esophageal, gallbladder, lung, and pancreatic SRCC, respectively (P < 0.001). Multivariate analyses showed that the primary tumor location was an independent prognostic factor of survival. Patients with lung, small intestine, and bladder SRCC had a comparable CSS to gastric SRCC, while breast and colorectal SRCC had better survival than gastric SRCC. Esophageal, gallbladder, and pancreatic SRCC were significantly associated with poor CSS compared with gastric SRCC. CONCLUSION: Our study suggests a major difference in survival of SRCC based on the primary tumor locations.

Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: A population-based analysis.

OBJECTIVE: To investigate the demographic features, clinicopathological characteristics and treatment outcomes of patients with nasopharyngeal carcinoma (NPC) according to age at diagnosis. METHODS: We assessed demographic and clinicopathological variables extracted from the Surveillance, Epidemiology, and End Results database (2004-2014). The Cox proportional hazards regression model was used to perform univariate and multivariate analyses of NPC-related mortality (cause-specific survival). RESULTS: A total of 3880 patients were analyzed. Median age was 55-years-old; 108 (2.8%), 508 (13.1%), 1876 (48.4%), 1240 (32.0%), and 148 (3.8%) patients were aged 1-19, 20-39, 40-59, 60-79, and 80-99-years-old, respectively. Younger patients tended to be black and present with poorly/undifferentiated disease and advanced tumor and nodal category compared to older patients. Younger patients were more likely to receive chemotherapy than older patients. In multivariate analyses, age at diagnosis was an independent prognostic factor for cause-specific survival. Increasing age at diagnosis was associated with a significantly higher risk of NPC-related mortality. Compared to patients aged 1-19-years-old, the hazard ratios for patients aged 20-39, 40-59, 60-79, and 80-99-years-old were 2.030 (95% confidence interval 1.004-4.104), 2.871 (1.474-5.590), 4.443 (2.273-8.683), and 12.024 (5.855-24.695), respectively. With the exception of black patients (P=0.100), older age was associated with poor survival in all demographic and clinical subgroups. CONCLUSION: Although younger patients tended to have advanced disease at diagnosis, older age at diagnosis was associated with a higher risk of NPC-related mortality.

Therapeutic effects of the smartphones and pads on hyperopia amblyopia of children / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the therapeutic effects of the fine sight training with the smartphones and pads on hyperopia amblyopia of children.METHODS:One hundred and twenty children (120 eyes) with hyperopia amblyopia were randomly divided into two groups in this prospective study.All the children in these two groups received the basic treatments of spectacle correction,penalization therapy and amblyopia trainings.The treatments of red-light blinking and grating as well as traditional fine sight training were used for the children in the control group.However,the smartphones and pads were applied instead of the traditional performances for the fine sight training in the experimental group.Best corrected visual acuity of every child was tested for every 3mo,to observe the time for the visual improvement and efficacy.RESULTS:In comparison with the control group,significant shorter time (80.54 ± 30.87d,P＜ 0.05) for promoted one line of LogMAR visual acuity and average treatment time (15.34±7.24mo,P＜0.05) were harvested in the experimental group.The efficacy in the experimental group was significantly higher than that in the control group (Z=-2.37,P=0.02).CONCLUSION:The fine sight training with the smartphones and pads can improve vison faster than traditional methods and decrease the time of therapy in children with hyperopia amblyopia,thus providing a new strategy for the treatment of hyperopia amblyopia.

Artificial induction of genetic competence in Bacillus amyloliquefaciens isolates.

OBJECTIVES: To induce natural genetic competence in Bacillus amyloliquefaciens isolates through overexpression of the master regulator, ComK, from B. subtilis (ComK Bsu ). RESULTS: Plasmid pUBXC carrying the xylose-inducible comK expression cassette was constructed using plasmid pUB110 as a backbone. Plasmid pUBXC could be transferred from B. subtilis to B. amyloliquefaciens through plasmid pLS20-mediated biparental conjugation. After being induced by xylose, four B. amyloliquefaciens strains harbouring plasmid pUBXC developed genetic competence. Under optimal conditions, the transformation efficiencies of plasmid DNA ranged from 129 ± 20.6 to 1.7 ± 0.1 × 105 cfu (colony-forming units) per µg DNA, and the transformation efficiencies of PCR-assembled deletion constructs ranged from 3.2 ± 0.76 to 3.5 ± 0.42 × 104 cfu per µg DNA in the four tested strains. CONCLUSION: Artificial induction of genetic competence through overexpressing ComK Bsu in B. amyloliquefaciens completed the tasks of replicative plasmid delivery and gene knockout via direct transformation of PCR-generated deletion cassettes.

Patterns of distant metastasis in Chinese women according to breast cancer subtypes.

To access possible relationships between breast cancer subtypes (BCS) and patterns of distant metastasis in advanced breast cancer. Breast cancer patients with distant metastasis at two academic centers from 2000-2015 were retrospectively reviewed. The breast cancer was classified into four subtypes: hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2) - (i.e., estrogen receptor [ER] + and/or progesterone receptor [PR] +, HER2-); HR+/HER2+ (ER+ and/or PR+, HER2+), HR-/HER2+ (ER- and PR-, and HER2+); and HR-/HER2- (ER- and PR-, and HER2-). A total of 679 patients were identified. The distribution of the BCS was 39.9% (271/679), 23.7% (161/679), 16.8% (114/679), and 19.6% (133/679) in HR+/HER2-, HR+/HER2+, HR-/HER2+, and HR-/HER2-, respectively. Patients with HR+/HER2+ and HR-/HER2+ subtypes were prone to abdominal and pelvic metastasis, those with HR+/HER2- and HR+/HER2+ subtypes were prone to bone metastasis, while patients with the HR-/HER2- subtype were prone to lung/mediastinal and brain metastases. In patients with pleural, axillary and/or neck lymph node, and other distant soft tissue metastases, there was no significant difference in metastatic patterns among the BCS. There are different patterns of distant metastasis associated with different BCS. There should be a different focus in the postoperative follow-up and monitoring of breast cancer patients with different BCS.