The efficacy and safety of anlotinib combined with platinum-etoposide chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A Chinese multicenter real-world study.

Background: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have high recurrence rates and bleak prognosis. This multicenter real-world study aimed to explore the efficacy and safety of anlotinib combined with platinum-etoposide chemotherapy as the first-line treatment of ES-SCLC. Methods: Pathologically confirmed ES-SCLC patients receiving anlotinib plus platinum-etoposide chemotherapy as the first-line treatment were enrolled in this retrospective study. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse reactions. The Cox regression analyses were employed to investigate the independent prognostic factors for OS and PFS of these individuals. Results: In total, 58 patients were included in this study. The median PFS was 6.0 months [95% confidence interval (CI): 3.5-8.5], and the median OS was 10.5 months (95%CI 8.7-12.3). Thirty-four patients achieved partial response (PR), 18 patients achieved stable disease (SD), and 6 patients achieved progressive disease (PD). The ORR and DCR were 58.6% and 89.6%. The main treatment-related adverse reactions were generally tolerated. Myelosuppression (44.8%) was the most common adverse reaction, followed by hypertension (41.4%), fatigue (34.5%), gastrointestinal reaction (32.7%), and hand-foot syndrome (24.1%). Multivariate analysis showed that post-medication hand-foot syndrome [PFS 8.5 vs. 5.5 months, Hazards Ratio (HR)=0.23, 95%CI 0.07-0.72, P =0.012] was the independent predictor of PFS, and hypertension (OS 15.9 vs. 8.3 months, HR=0.18, 95%CI 0.05-0.58, P =0.005) was the independent predictor of OS. Conclusion: Anlotinib combined with platinum-etoposide chemotherapy as the first-line treatment for ES-SCLC appears to be effective and well-tolerated in the real-world. Well-designed large-scale prospective studies are urgently needed in the future to verify our findings.

The Efficacy and Safety of Anlotinib in Extensive-Stage Small Cell Lung Cancer: A Multicenter Real-World Study.

Purpose: Anlotinib, an antiangiogenic multi-target tyrosine kinase inhibitor (TKI), has shown favorable anticancer efficacy and acceptable safety in treating extensive-stage small cell lung cancer (ES-SCLC) in some clinical studies. This research aimed to explore the real-world efficacy and safety of anlotinib in ES-SCLC. Methods: Pathologically confirmed ES-SCLC patients receiving anlotinib were enrolled for this retrospective study. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse reactions. Results: In total, 202 patients were included in this study. The median PFS of all patients was 4.8 months [95% confidence interval (CI): 3.9-5.7], and the median OS was 7.6 months (95% CI 6.5-8.7). Respectively, the overall ORR and DCR were 30.2% and 87.1%. The univariate and multivariate Cox regression analyses revealed that patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1, plus chemotherapy or immunotherapy, plus radiotherapy, and post-medication hypertension might have longer PFS and OS. The PFS and OS were significantly prolonged in combination group than that in monotherapy group [PFS 6.0 vs 3.6 months, hazards ratio (HR)=0.49, 95% CI 0.34-0.70, P < 0.001; OS 9.2 vs 4.8 months, HR = 0.48, 95% CI 0.32-0.72, P < 0.001]. The main treatment-related adverse reactions were generally tolerated. The incidence of adverse reactions in combination group was higher than that in monotherapy group (75.0% vs 52.6%, P = 0.001). The most common adverse reaction was hypertension, followed by hand-foot syndrome and fatigue, regardless of monotherapy or combination group. Conclusion: Anlotinib is effective and well tolerated in patients with ES-SCLC in the real-world. The clinical efficacy of anlotinib combined with chemotherapy or immunotherapy is better than that of monotherapy. Further investigations are needed for prospective studies with larger sample size.

Assessment of the Clinical Utility of Circulating Tumor Cells at Different Time Points in Predicting Prognosis of Patients With Small Cell Lung Cancer: A Meta-Analysis.

OBJECTIVES: Numerous studies have elucidated that circulating tumor cells (CTCs) have significant prognostic value in various solid tumors. However, the prognostic value of CTCs in small cell lung cancer (SCLC) remains controversial. The current study was performed to investigate the prognostic significance of different time points of CTCs in SCLC. METHODS: PubMed, EMBASE, Web of Science, and Cochrane Library databases were retrieved for eligible studies. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the association between CTCs level and overall survival (OS) and progression-free survival (PFS) in SCLC. Furthermore, subgroup analyses, sensitivity analysis, Begg's and Egger's tests were also conducted. RESULTS: Sixteen cohort studies with 1103 participants were eligible for this meta-analysis. Our results revealed that higher pretreatment CTCs level was significantly correlated with worse OS in SCLC no matter CellSearch (HR, 2.95; 95%CI, 1.56-5.58; P = .001) or other methods (HR, 2.37; 95%CI, 1.13-4.99; P = .023) was used to detect CTCs. Higher pretreatment CTCs status detected by CellSearch was associated with shorter PFS (HR, 3.75; 95%CI, 2.52-5.57; P < .001), while there was no significant association when other methods were adopted to CTC detection (HR, 2.04; 95%CI, .73-5.68; P = .172). Likewise, we observed that higher post-therapy CTCs level detected by both CellSearch (HR, 2.99; 95%CI, 1.51-5.93; P = .002) and other methods (HR, 4.79; 95%CI, 2.03-11.32; P < .001) was significantly correlated with decreased OS in SCLC. However, higher post-therapy CTCs count detected by CellSearch was not correlated with worse PFS (HR, 1.80; 95%CI, .83-3.90; P = .135). Sensitivity analysis demonstrated that the pooled data were still stable after eliminating studies one by one. However, significant publication bias was observed between pretreatment CTCs level detected by CellSearch and OS of SCLC. CONCLUSION: Dynamic monitoring of CTCs level could be a non-invasive and effective tool to predict the disease progression and prognosis in patients with SCLC.

Occurrence and dietary exposure assessment of pentachlorophenol in livestock, poultry, and aquatic foods marketed in Guangdong Province, China: Based on food monitoring data from 2015 to 2018.

As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in the Guangdong Province (GD) of China, and the resultant dietary exposure have not been elucidated. To address this gap, 3,100 samples from seven food categories, including beef, pork, mutton, offals, broilers, hen eggs, and farmed freshwater fish, marketed throughout four geographical regions of GD, were collected from 2015 to 2018. Gas chromatography coupled with mass spectrometry was employed to detect PCP levels in these food matrices. PCP was found in all food categories, but the average contamination levels were low, ranging from 0.40 µg/kg wet weight (ww) (hen eggs) to 5.85 µg/kg ww (offals). However, higher concentrations of PCP were detected (P < 0.05) in animal source food from the North region. Additionally, a temporal declining trend was observed in this four-year consecutive survey. The estimated human dietary exposure of PCP to population groups, including the general population and subgroups (male and female, children, and adults), was found to be far below the permissible daily intake (3 µg/kg body weight). Therefore, the health impacts of PCP should be correspondingly low for local residents, based on current toxicological knowledge. Regional exposure patterns varied due to different extents of contamination in the four areas, and pork, broilers, and freshwater fish were the major sources of dietary PCP exposure. PRACTICAL APPLICATION: As a persistent organic pollutant, pentachlorophenol (PCP) has serious impacts on human health. However, its presence in animal source food products sold in Guangdong Province of China, and the resultant dietary exposure have not been elucidated. In this study, we conducted an in-depth investigation on the occurrence of PCP in major foodstuff categories, including beef, pork, mutton, broilers, offals, hen eggs, and farmed freshwater fish, marketed in all 21 prefecture-level divisions of Guangdong Province, in order to provide integral insights for regulatory authorities.

Tumor Mutation Burden, Immune Cell Infiltration, and Construction of Immune-Related Genes Prognostic Model in Head and Neck Cancer.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the prognosis of HNSCC remains bleak. Numerous studies revealed that the tumor mutation burden (TMB) could predict the survival outcomes of a variety of tumors. Objectives: This study aimed to investigate the TMB and immune cell infiltration in these patients and construct an immune-related genes (IRGs) prognostic model. Methods: The expression data of 546 HNSCC patients were obtained from The Cancer Genome Atlas (TCGA) database. All patients were divided into high- and low- TMB groups, and the relationship between TMB and clinical relevance was further analyzed. The differentially expressed genes (DEGs) were identified using the R software package, limma. Functional enrichment analyses were conducted to identify the significantly enriched pathways between two groups. CIBERSORT algorithm was adopted to calculate the abundance of 22 leukocyte subtypes. The IRGs prognostic model was constructed via the multivariate Cox regression analysis. Results: Missense mutation and single nucleotide variants (SNV) were the most predominant mutation types in HNSCC. TP53, TTN, and FAT1 were the most frequently mutated genes. Patients with high TMB were observed with worse survival outcomes. The functional analysis of TMB associated DEGs showed that the identified DEGs mainly involved in spliceosome, RNA degradation, proteasome, and RNA polymerase pathways. We observed that macrophages, T cells CD8, and T cells CD4 memory were the most commonly infiltrated subtypes of immune cells in HNSCC. Finally, an IRGs prognostic model was constructed, and the AUC of the ROC curve was 0.635. Conclusions: Our results suggest that high TMB is associated with poor prognosis in HNSCC patients. The constructed model has potential prognostic value for the prognosis of these individuals, and it needs to be further validated in large-scale and prospective studies.

The prognostic value of pretreatment prognostic nutritional index in patients with small cell lung cancer and it's influencing factors: a meta-analysis of observational studies.

BACKGROUND: Numerous studies identified that pretreatment prognostic nutritional index (PNI) was significantly associated with the prognosis in various kinds of malignant tumors. However, the prognostic value of PNI in small cell lung cancer (SCLC) remains controversial. We performed the present meta-analysis to estimate the prognostic value of PNI in SCLC and to explore the relationship between PNI and clinical characteristics. METHODS: We systematically and comprehensively searched PubMed, EMBASE, and Web of Science for available studies until April 17, 2020. Pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to evaluate the correlation between PNI and overall survival (OS) and progression-free survival (PFS) in SCLC. Odds ratios (ORs) and 95% CIs were applied to evaluate the relationship between clinical features and PNI in SCLC. RESULTS: A total of nine studies with 4,164 SCLC patients were included in the meta-analysis. The pooled data elucidated that lower PNI status was an independent risk factor for worse OS in SCLC (HR =1.43; 95% CI: 1.24-1.64; P<0.001), while there was no significant correlation between PNI status and PFS (HR =1.44; 95% CI: 0.89-2.31; P=0.134). We also found that Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (OR =2.72; 95% CI: 1.63-4.53; P<0.001) and extensive-stage (ES) disease (OR =1.93; 95% CI: 1.62-2.30; P<0.001) were risk factors for low PNI, while prophylactic cranial irradiation (PCI) (OR =0.53; 95% CI: 0.40-0.69; P<0.001) was a protective factor for low PNI. CONCLUSIONS: Our findings suggested that low PNI status was closely correlated with the decreased OS in SCLC. Surveillance on PNI, amelioration of nutritional and immune status, and timely initiation of PCI may improve the prognosis of SCLC.

Clinical outcomes and prognostic factors in bloodstream infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae among patients with malignancy: a meta-analysis.

BACKGROUND: The colonization of Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) in bloodstream infections (BSIs) has been increased dramatically worldwide, and it was associated with worse clinical outcomes in patients with malignancy. We performed the meta-analysis to investigate the prognosis and risk factors in BSIs caused by ESBL-PE in oncological patients. METHODS: PubMed, EMBASE, and Cochrane Library were searched for related studies. All-cause mortality was considered as the primary outcome. Subgroup analyses, meta-regression analyses, and sensitivity analysis were used to investigate heterogeneity and reliability in results. RESULTS: 6,729 patients from 25 studies were eligible. Six studies enrolled oncological patients with BSIs caused by ESBL-PE only, while 19 studies both enrolled ESBL-PE and non-ESBL-PE infections. The results showed that BSIs caused by ESBL-PE in patients with malignancy was associated with higher mortality than non-ESBL-PE infections (RR = 2.21, 95% CI: 1.60-3.06, P < 0.001), with a significant between-study heterogeneity (I2 =78.3%, P < 0.001). Subgroup analyses showed that children (RR = 2.80, 95% CI: 2.29-3.43, P < 0.001) and hematological malignancy (RR = 3.20, 95% CI: 2.54-4.03, P < 0.001) were associated with a higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality. CONCLUSIONS: Our study identified that BSIs caused by ESBL-PE in patients with malignancy were associated with worse clinical outcomes compared with non-ESBL-PE infections. Furthermore, children and hematological malignancy were associated with higher mortality. Severe sepsis/ septic shock, pneumonia, and ICU admission were the most common predictors of mortality.

Nosocomial Infections in Gastrointestinal Cancer Patients: Bacterial Profile, Antibiotic Resistance Pattern, and Prognostic Factors.

BACKGROUND: Cancers of the gastrointestinal (GI) tract and its associated excretory glands are one of the most common causes of cancer-related death worldwide, and these patients are more likely to developing nosocomial infections due to immunodeficiency. OBJECTIVE: To explore the bacterial profile, antibiotic resistance pattern, and prognostic factors of nosocomial infections in hospitalized GI cancer patients. METHODS: All electronic medical records of nosocomial infection episodes in hospitalized GI cancer patients were retrospectively reviewed. In-hospital mortality was used to evaluate the prognosis of patients. Mann-Whitney test, Chi-square test, and binary logistic regression analysis were used to identify potential risk factors for in-hospital mortality. P-values <0.05 were considered statistically significant. RESULTS: A total of 428 GI cancer patients developed nosocomial infections during hospitalization. Respiratory tract infections (44.2%), bloodstream infections (BSIs) (11.7%), and abdominal cavity infections (11.4%) were the most common infection sites. The predominant causative pathogens were extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (13.6%), ESBL-negative E. coli (11.9%), and Klebsiella pneumoniae (10.0%). Multidrug-resistant (MDR) strains were detected in 27.6% of isolates. Antimicrobial susceptibility analysis showed that the isolated Gram-negative bacteria (GNB) exhibited high sensitivity to amikacin, meropenem, imipenem, and piperacillin/tazobactam, while the isolated Gram-positive bacteria exhibited high sensitivity to tigecycline, linezolid, and vancomycin. The overall in-hospital mortality of all patients was 11.2% in the study. Multivariate analysis showed that ECOG performance status ≥two scores, length of antibiotic treatment <9.0 days, existence of septic shock, and hypoproteinemia were independent risk factors for in-hospital mortality. CONCLUSION: The burden of nosocomial infections in GI cancer patients is considerably high, with GNB being predominantly isolated causative pathogens. Surveillance on serum albumin level, adequate antibiotic treatment, early identification, and prompt treatment of septic shock could benefit the prognosis.

Nosocomial infections due to multidrug-resistant bacteria in cancer patients: a six-year retrospective study of an oncology Center in Western China.

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.

Physical, antioxidant and structural characterization of blend films based on hsian-tsao gum (HG) and casein (CAS).

The effects of hsian-tsao gum (HG) addition on the physical properties, antioxidant activities and structure of casein (CAS) film have been investigated. It has been observed that HG addition provided CAS film with better mechanical properties and resistant to moisture, stronger barrier properties against light and higher antioxidant activities than pure CAS film. Fourier transformation infrared (FTIR) data indicated that hydrogen bonding interactions and Maillard reactions occurred between CAS and HG, giving rise to a more compact structure than CAS film. The results of X-ray diffraction and differential scanning calorimetry (DSC) indicated that CAS and HG were compatible, and addition of HG destroyed the original crystalline domains of CAS film, and the blend films exhibited higher glass transition temperatures than CAS film. Moreover, nuclear magnetic resonance (NMR) analysis showed that HG addition significantly changed the mobility of water molecule in CAS film. Especially, ratio of the high mobility water of CAS/HG films significantly decreased as compared to CAS film.

Antitumor and immunomodulating activity of a polysaccharide from Sophora flavescens Ait.

The immunostimulatory activity of Sophora flavescens polysaccharide (SFPW1) was evaluated by using in vitro cell models and in vivo animal models. The results demonstrated that SFPW1 could effectively inhibit the tumor growth in H22 tumor-bearing mice and promote the splenocyte proliferation, thus resulting in a prolonged life survival. For assay in vitro, SFPW1 significantly strengthened peritoneal macrophages to devour H22 tumor cells and stimulated macrophages to produce nitric oxide (NO) via up-regulation of inducible NO synthase (iNOS) activity. However, no direct cytotoxicity against H22 tumor cells was observed in vitro. These results suggest that SFPW1 might be a strong natural immunomodulator and the antitumor effect of this polysaccharide is associated with its potent immunostimulating effect.

[Study on the timeliness of the notifiable communicable diseases surveillance system in Fujian province, China, 2004].

OBJECTIVE: To understand the timeliness of the notifiable communicable diseases surveillance system in Fujian province. METHODS: Database from the internet based communicable diseases reporting system was used. RESULTS: The 50th percentile of time between the disease diagnosed and report recorded in medical faculties was 1 day in 2004 which was 6 days less than that in 2001 - 2003. The timeliness rate of 0 day was 46.46%, a 2.7 times over that in 2001 - 2003. The timeliness of notifiable communicable diseases surveillance system in different administrative areas, reporting units and on different diseases was significantly different. Time between the disease diagnosed and report recorded was the shortest in those cases reported by hospitals and traditional Chinese medicine(TCM) hospitals at the county level and above, with 50th percentile as 0 day, but the timeliness rate of 0 day was 50.76% with 70.04% of the cases were reported from hospitals and TCM hospitals of county level and above. Length between the disease diagnosed and reported was the longest in those cases recorded by Centers for Disease Control and Prevention(CDCs) with the 50th percentile as 3 days. The source of cases recorded by CDCs came from hospitals at the township level, where there was no connection to internet but the reporting cards had to be sent to local CDCs. Time between the disease being diagnosed and reported was 2 days in those cases reported by hospitals at the township level. 21.21% of cases were recorded by hospitals of township level and CDCs. The 50th percentile of time shown between the reported records and confirmed by CDCs was 4 hours The 24 hour timeliness rate was 63.65%. CONCLUSION: The timeliness of the notifiable communicable diseases surveillance system had been improved significantly after the medical personnel recording the cases directly through internet. Timeliness could be further improved through access to internet at the hospitals of township level, training of staff and better hospital management systems.