Correlation of Increased Soluble Tumor Necrosis Factor Receptor 1 with Mortality and Dependence on Treatment in Non-Small-Cell Lung Cancer Patients: A Longitudinal Cohort Study.

BACKGROUND: Tumor necrosis factor (TNF) is a multipotent cytokine involved in inflammation and anti-tumor activity. TNF-α exerts its function upon binding to TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2). This study investigates the relationship of soluble (s) TNF-R1 levels in non-small-cell lung cancer (NSCLC) patients with treatment and overall survival. METHODS: In total, 134 NSCLC patients treated at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019 were included in this study. Serum levels of sTNF-R1 were measured via ELISA at baseline and during and after treatment. A linear mixed-effects model was used to assess sTNF-R1 changes over time. Linear regression was applied to investigate the association between clinical characteristics and changes in sTNF-R1. Cox regression models were used to estimate associations with overall mortality. RESULTS: The estimated average sTNFR-1 at baseline was 2091.71 pg/mL, with a change of 6.19 pg/mL per day. Cox models revealed that the individual change in sTNF-R1 was more strongly associated with mortality than its baseline value, especially after adjusting for covariates. CONCLUSIONS: This study provides evidence that the individual change in sTNF-R1 levels during and after treatment were associated with the risk of mortality, suggesting the use of the sTNF-R1 trajectory as a prognostic marker.

Treatment patterns in stage III non­small­cell lung cancer patients: a population­based study using German cancer registry data.

PURPOSE: Lung cancer remains the leading cause of cancer-related mortality worldwide, mostly due to delayed diagnosis. The objective of this study is to examine the treatment patterns and overall survival (OS) outcomes in a cohort of patients diagnosed with stage III non-small cell lung cancer (NSCLC) over a period of 12 years in Germany. METHODS: This retrospective study is based on German cancer registry data and included 14,606 stage III NSCLC patients diagnosed during 2007-2018. Three time-periods were defined according to the availability of advanced diagnostic and treatment strategies (2007-2010 low availability era (LAE), 2011-2014 transition era (TE), 2015-2018 modern era (ME)). Patients were categorized according to the treatment they received during those eras. Kaplan-Meier curves and multivariate Cox proportional hazards models were used to investigate the association between being diagnosed during a certain era and survival. The hazard ratio (HR) estimates were reported along with the 95% confidence interval (CI). RESULTS: The median OS rose from 16 months in the LAE to 22 months in the ME. The HR for patients diagnosed and treated in the ME was estimated to be [0.78; 95% CI (0.74-0.83)] compared to those diagnosed and treated in LAE. The benefit was most evident for patients treated by radiotherapy and chemotherapy [HR 0.73 95% CI (0.66-0.82)]. CONCLUSION: This study highlights the importance of diagnostic and treatment advances in improving outcomes for lung cancer patients. Further studies are needed to assess progress in survival rates with current immunotherapy integration.

Suboptimal use of hormonal therapy among German men with localized high-risk prostate Cancer during 2005 to 2015: analysis of registry data.

BACKGROUND: This study assesses the use of hormonal therapy to treat high-risk localized prostate cancer (HRLPCa) cases diagnosed between 2005 and 2015. METHODS: All N0-XM0 with ≥T3a, or PCa cases with poorly differentiated feature (equivalent to Gleason score ≥ 8), diagnosed between 2005 and 2015 were extracted from German population-based cancer registries. Cases treated by surgery or chemotherapy were excluded. Description of hormonal therapy use by HRLPCa cases' profile was presented. Relative risk (RR) was computed with a log-link function to identify factors associated with hormonal therapy use among radiotherapy-treated HRLPCa cases. RESULTS: A total of 5361 HRLPCa cases were analyzed. Only 27.6% (95% confidence interval [CI]: 26.4-28.8%) of the HRLPCa cases received hormonal therapy in combination with radiotherapy. The use of combined hormonal therapy and radiotherapy varied from 19.8% in Saxony to 47.8% in Schleswig-Holstein. Application of hormonal therapy was higher for the locally advanced cases compared to the poorly differentiated cases (relative risk [RR] = 1.28; 95%CI: 1.19, 1.37). Older patients showed a slightly increased use of hormonal therapy (RR for a 10-year age increase = 1.09; 95%CI: 1.02, 1.16). Compared to PCa cases from the most affluent residential areas, cases from the least affluent (RR = 0.71; 95%CI: 0.55, 0.92) and medium (RR = 0.75; 95%CI: 0.58, 0.96) areas had decreased use of hormonal therapy. The introduction of the German S3-guideline did not make a marked difference in the uptake of both hormonal therapy and radiotherapy (RR = 1.02; 95%CI: 0.95, 1.09). CONCLUSION: This study found a low use of hormonal therapy among HRLPCa patients treated without surgery. The introduction of the German S3-guideline for prostate cancer treatment does not seem to have impacted hormonal therapy use.

Socioeconomic disparities in endometrial cancer survival in Germany: a survival analysis using population-based cancer registry data.

PURPOSE: Area-based socioeconomic deprivation has been established as an important indicator of health and a potential predictor of survival. In this study, we aimed to measure the effect of socioeconomic inequality on endometrial cancer survival. METHODS: Population-based data on patients diagnosed with endometrial cancer between 2004 and 2014 were obtained from the German Centre for Cancer Registry Data. Socioeconomic inequality was defined by the German Index of Socioeconomic Deprivation. We investigated the association of deprivation and overall survival through Kaplan-Meier curves and Cox proportional regression models. RESULTS: A total of 21,602 women, with a mean age of 67.8 years, were included in our analysis. The observed 5-year overall survival time for endometrial cancer patients living in the most affluent districts (first quintile) was 78.6%. The overall survival rate decreased as the level of deprivation increased (77.2%, 73.9%, 76.1%, 74.7%, for patients in the second, third, fourth, and fifth quintile (most deprived patients), respectively). Cox regression models showed stage I patients living in the most deprived districts to have a higher hazard of overall mortality when compared to the cases living in the most affluent districts [Hazard ratio: 1.20; 95% Confidence interval (0.99-1.47)] after adjusting for age, tumor characteristics, and treatment. CONCLUSION: Our results indicate differences in endometrial cancer survival according to socioeconomic deprivation among stage I patients. Considering data limitations, future studies with access to individual-level patient information should be conducted to examine the underlying causes for the observed disparity in cancer survival.

The effect of home visits as an additional recruitment step on the composition of the final sample: a cross-sectional analysis in two study centers of the German National Cohort (NAKO).

BACKGROUND: Participation in epidemiologic studies has been declining over the last decades. In addition to postal invitations and phone calls, home visits can be conducted to increase participation. The aim of this study was therefore to evaluate the effects of home visits in terms of response increase and composition of the additionally recruited and final sample. METHODS: In the framework of the German National Cohort (NAKO) recruitment process, two of 18 study centers, Halle (Saale) and Berlin-Center, performed home visits as additional recruitment step after postal invitation and reminders. Response increase was calculated and differences between participants recruited via home visits and standard recruitment were examined. Proportions are presented as percentages with 95%-confidence intervals. RESULTS: In the general population in Halle, 21.3-22.8% participated after postal invitation and two reminders in the five assessed recruitment waves. The increase of the overall response was 2.8 percentage points (95%confidence interval: 1.9-4.0) for home visits compared to 2.4 percentage points (95%CI: 1.7-3.3) for alternatively sent third postal reminder. Participants recruited via home visits had similar characteristics to those recruited via standard recruitment. Among persons of Turkish descent in Berlin-Center site of the NAKO, home visits conducted by native speakers increased the participation of women, persons living together with their partner, were born in Turkey, had lower German language skills, lower-income, lower education, were more often smokers and reported more often diabetes and depression to a degree which changed overall estimates for this subsample. CONCLUSIONS: As an additional recruitment measure in the general population, home visits increased response only marginally, and the through home visits recruited participants did not differ from those already recruited. Among persons with migration background, home visits by a native speaker increased participation of persons not reached by the standard recruitment, but the effects of using a native speaker approach could not be separated from the effect of home visits.

Patterns of glioblastoma treatment and survival over a 16-years period: pooled data from the German Cancer Registries.

INTRODUCTION: Glioblastoma multiforme (GBM) is a primary malignant brain tumour characterized by a very low long-term survival. The aim of this study was to analyse the distribution of treatment modalities and their effect on survival for GBM cases diagnosed in Germany between 1999 and 2014. METHODS: Cases were pooled from the German Cancer Registries with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes for GBM or giant-cell GBM. Three periods, first (January 1999-December 2005), second (January 2006-December 2010) and a third period (January 2011-December 2014) were defined. Kaplan-Meier plots with long-rank test compared median overall survival (OS) between groups. Survival differences were assessed with Cox proportional-hazards models adjusted for available confounders. RESULTS: In total, 40,138 adult GBM cases were analysed, with a mean age at diagnosis 64.0 ± 12.4 years. GBM was more common in men (57.3%). The median OS was 10.0 (95% CI 9.0-10.0) months. There was an increase in 2-year survival, from 16.6% in the first to 19.3% in the third period. When stratified by age group, period and treatment modalities, there was an improved median OS after 2005 due to treatment advancements. Younger age, female sex, surgical resection, use of radiotherapy and chemotherapy, were independent factors associated with better survival. CONCLUSION: The inclusion of temozolomide chemotherapy has considerably improved median OS in the older age groups but had a lesser effect in the younger age group of cases. The analysis showed survival improvements for each treatment option over time.

Corrosion Inhibition of Carbon Steel in Hydrochloric Acid Solution Using Ethoxylated Nonionic Surfactants Based on Schiff Base: Electrochemical and Computational Investigations.

Two ethoxylated nonionic surfactants (L400 and L600) based on Schiff base are prepared from polyoxyethylene, glyoxalic acid, and phenylenediamine. They are evaluated electrochemically as carbon steel corrosion inhibitors in 1 M HCl by electrochemical impedance spectroscopy (EIS) and Tafel techniques and complemented with microscopic analysis methods. The obtained Tafel data indicate the mixed-type behavior of the inhibitor used. The inhibition efficiency touches the peak at 1 × 10-4 M, exhibiting 92 and 94% for L400 and L600, respectively. The presence of the tested inhibitors decreases corrosion current density (i corr) and double-layer capacitance (C dl) due to the formation of a protective adsorption layer in place of the already adsorbed water and aggressive Cl- ions. Both L400 and L600 adsorption modes follow Langmuir adsorption isotherm. The density functional theory (DFT) calculated indices (ΔE gap and E HOMO) indicate the superiority of L600 over the L400 counterpart as a reactive compound. Adsorption of L600 and L400 over the Fe(1 1 0) in simulated acidic medium is investigated by Monte Carlo (MC) simulation to verify their inhibition performance and are matched with adsorption free energy ΔG ads calculated values. Both experimental and theoretical data are in agreement.

Socioeconomic disparities in head and neck cancer survival in Germany: a causal mediation analysis using population-based cancer registry data.

PURPOSE: Despite recent improvements in cancer treatment in Germany, a marked difference in cancer survival based on socioeconomic factors persists. We aim to quantify the effect of socioeconomic inequality on head and neck cancer (HNC) survival. METHODS: Information on 20,821 HNC patients diagnosed in 2009-2013 was routinely collected by German population-based cancer registries. Socioeconomic inequality was defined by the German Index of Socioeconomic Deprivation. The Cox proportional regression and relative survival analysis measured the survival disparity according to level of socioeconomic deprivation with respective confidence intervals (CI). A causal mediation analysis was conducted to quantify the effect of socioeconomic deprivation mediated through medical care, stage at diagnosis, and treatment on HNC survival. RESULTS: The most socioeconomically deprived patients were found to have the highest hazard of dying when compared to the most affluent (Hazard Ratio: 1.25, 95% CI 1.17-1.34). The most deprived patients also had the worst 5-year age-adjusted relative survival (50.8%, 95% CI 48.5-53.0). Our mediation analysis showed that most of the effect of deprivation on survival was mediated through differential stage at diagnosis during the first 6 months after HNC diagnosis. As follow-up time increased, medical care, stage at diagnosis, and treatment played no role in mediating the effect of deprivation on survival. CONCLUSION: This study confirms the survival disparity between affluent and deprived HNC patients in Germany. Considering data limitations, our results suggest that, within six months after HNC diagnosis, the elimination of differences in stage at diagnosis could reduce survival inequalities.

3-(Bromoacetyl)coumarins: unraveling their synthesis, chemistry, and applications.

This review emphasizes recent developments in synthetic routes of 3-(bromoacetyl)coumarin derivatives. Also, chemical reactions of 3-(bromoacetyl)coumarins as versatile building blocks in the preparation of critical polyfunctionalized heterocyclic systems and other industrially significant scaffolds are described. Recent advances of 3-(bromoacetyl)coumarins as attractive starting points towards a wide scale of five and six-membered heterocyclic systems such as thiophenes, imidazoles, pyrazoles, thiazoles, triazoles, pyrans, pyridines, thiadiazins as well as fused heterocyclic systems have been reported. Additionally, this review covers a wide range of analytical chemistry, fluorescent sensors, and biological applications of these moieties, covering the literature till May 2021.

Meta-analysis of the longevity of commonly used pit and fissure sealant materials.

OBJECTIVE: This systematic literature review and meta-analysis compared the clinical retention of primed or adhesively bonded sealants to that of conventional sealant materials. METHODS: A search of the MEDLINE, EMBASE and CENTRAL databases identified 3707 abstracts published prior to 12/31/2017, of which 335 clinical publications were analysed in detail. A total of 67 studies included information about sealant retention after 24, 36, or 60 months of follow-up. A meta-analysis using a random effects model was conducted to calculate the pooled estimate of the retention rates for the five groups of sealants. Subgroup moderator analysis was performed to compare the pooled retention rate estimate (RRE) of primed sealants against those of the other groups. RESULTS: Primed sealants had a 2-year pooled RRE of 43.2% (95% CI: 30.5-55.8), which was significantly inferior to those of auto-polymerizing (80.8%, 95% CI: 72.2-89) and light-polymerizing sealants (68.4%, 95% CI: 60.2-76.7). Fluoride-releasing and light-polymerizing sealants had the highest 3-year pooled RREs (86.4%, 95% CI: 73.4-99.3 and 83.1%, 95% CI: 75.6-90.7, respectively). SIGNIFICANE: The results of this meta-analysis suggest that primed sealants cannot be fully recommended for clinical practice due to their moderate survival rates. Auto-polymerizing, light-polymerizing and fluoride-releasing sealants continue to be considered the reference standards for pit and fissure sealants. However, future generations and developments of primed sealant materials may change this position.

Lung Cancer Attributed Mortality Among 316,336 Early Stage Breast Cancer Cases Treated by Radiotherapy and/or Chemotherapy, 2000-2015: Evidence From the SEER Database.

OBJECTIVE: To estimate the risk of death from lung cancer in patients treated for breast cancer (BC) in relation to the general population. METHODS: BC data, covering 2000 to 2015, were extracted from the Surveillance, Epidemiology and End Results-18 (SEER-18) cancer registry database. A comparison of lung cancer attributed mortality between BC patients and the general population was performed using standardized mortality ratios (SMRs) and SMRs conditional on survival length (cSMRs). Prognostic factors of lung cancer mortality were identified using flexible parametric modelling. Our model adjusts the effect of downstream (histopathological BC tumor grade and hormone receptor status) and upstream (age at diagnosis, ethnicity, and marital status) factors. RESULTS: The median follow-up was 6.4 years (interquartile range, 3.0-10.3 years). BC cases who received only radiotherapy (cSMR = 0.93; 95%CI: 0.77-1.13), only chemotherapy (cSMR = 0.91; 0.62-1.33), and radio-and chemotherapy (cSMR = 1.04; 0.77-1.39) had no evidence of increased lung cancer mortality relative to the general population. The adjusted model identified that lung cancer mortality was higher for women who were older at diagnosis compared to those <50 years (ranging from HR50-59 = 3.41 [95%CI: 2.72-4.28] to HR70-79 = 10.53 [95%CI: 8.44-13.13]) and for cases with negative estrogen and progesterone receptors (HR =1.38; 95% CI: 1.21-1.57). Compared to married cases, widowed, divorced, single or others had a 76%, 45%, and 25% higher hazard of lung cancer mortality, respectively. Lung cancer mortality was lower for American Indian/Alaska Native and Asian/Pacific Islander ethnicities (HR = 0.51; 95% CI: 0.40-0.64) compared to BC cases with white ethnic background. CONCLUSIONS: There is no evidence for a higher lung cancer mortality in BC patients when compared to the general population.