Influence of omega- 3 fatty acids, soya isoflavones and their combination for abrogating carbon tetrachloride hazards in male rats.

Studies have shown that carbon tetrachloride (CCl4) induces hepatic and renal damage arising from oxidative stress. The present study was undertaken to examine the effect of omega-3 fatty acids and/or soya isoflavones on CCl4 induced toxicity in male albino rat liver and kidney. For this purpose, 42 rats were divided as follows: group 1, rats serves as the control without any treatment; group 2, rats were administered a single dose of CCl4 intraperitoneally (1 mg/kg b. wt.); group 3, rats were supplemented daily with omega-300 orally (400 mg/kg b. wt.); group 4, rats were supplemented daily with pro-S orally (50 mg/kg b. wt.); group 5, rats were supplemented daily with omega-300 orally for four weeks, then after 24 hours treated with a single dose of CCl4 at the same tested doses. group 6, rats were supplemented daily with pro- S orally for four weeks, then after 24 hours treated with a single dose of CCl4 at the same tested doses; group 7, rats were supplemented daily with an oral combination of omega-300 and pro-S orally for four weeks, then after 24 hours treated with a single dose of CCl4 at the same tested doses. Results showed that CCl4 administration induces hepatic damage indicated by a significant increase in the activities of alkaline phosphatase (ALP), aspartate aminotransferase (AST) and Aalanine aminotransferase (ALT) enzymes and glucose level, with a significant increase in malondialdehyde (MDA) and nitric oxide (NO) levels and a significant decrease of reduced glutathione (GSH) level in liver tissue. Also, CCl4 toxicity induce renal damage manifested in a significant increase in serum urea, creatinine, uric acid, and oxidative stress of kidney tissue reflected by increase of MDA, NO and the decrease of GSH levels. The pre-treatment with omega-3 fatty acids and/or soya isoflavones revealed ameliorative effect against deleterious effects of CCl4 toxicity on hepatic and renal tissues and all tested parameters. Results of the current study revealed also that the pre-treatment with omega-3 fatty acids and/or soya isoflavones to rats improved liver and kidney function and produced high antioxidant activity.

Hematological and renoprotective effects of folic acid and lentil extract in diclofenac sodium exposed rats / Efeitos hematológicos e renoprotetores do ácido fólico e do extrato de lentilha em ratos expostos ao diclofenaco de sódio

Excessive intake of non-steroidal anti-inflammatory drugs such as, diclofenac sodium (DS) may lead to toxicity in the rats. In this work, we aimed to examine the protective impact of lentil extract (LE) and folic acid (FA) on the hematological markers, the kidney tissue oxidative stress and the renal function against diclofenac sodium (DS) in male albino rats. The rats (120-150 g) were divided into four equal groups randomly, the first group kept as the untreated control. The second group was administrated with DS (11.6 mg/kg b.wt. orally once/day). The third group was received DS+FA (11.6 mg/kg b.wt.+76.9 microgram/kg b.wt.) orally once/day. The fourth group was treated with DS+LE (11.6 mg/kg b.wt.+500 mg/kg b.wt.) orally once/day. After four weeks, the results revealed that DS produced a significant decrease in the values of red blood cells (RBCs), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBCs). On the other hand, there was a significant increase in the platelets count. Also, DS induced a renal deterioration; this was evidenced by the significant increase in the serum levels of urea, creatinine, uric acid, Na, Ca, Mg as well as the nitric oxide (NO) level in the kidney tissue. Also, there were a significant reduction in the serum levels of potassium (K) and reduced glutathione (GSH) in the kidney homogenates. Moreover, the findings in the rats treated by DS+LE or DS+FA showed a potential protection on the hematological markers, oxidative stress in the kidney tissue and the renal function disturbed by DS. LE and FA could play a potent role for the prevention the adverse hematological, the kidney tissue oxidative stress and the renal dysfunction caused by DS via their anti-oxidative and bioactive phytochemicals.

A ingestão excessiva de anti-inflamatórios não esteroidais, como o diclofenaco de sódio (DS), pode causar toxicidade em ratos. Neste trabalho, objetivamos examinar o impacto protetor do extrato de lentilha (LE) e ácido fólico (AF) em marcadores hematológicos, no estresse oxidativo do tecido renal e na função renal contra o diclofenaco de sódio (DS) em ratos albinos machos. Os ratos (120-150 g) foram divididos em quatro grupos iguais aleatoriamente, sendo o primeiro grupo mantido como controle não tratado. O segundo grupo foi administrado com DS (11,6 mg / kg de peso corporal por via oral uma vez / dia). O terceiro grupo recebeu DS + FA (76,9 mg / kg de peso corporal por via oral uma vez / dia). O quarto grupo foi tratado com DS + LE (500 mg / kg de peso corporal por via oral uma vez / dia). Após quatro semanas, os resultados revelaram que o DS produziu uma diminuição significativa nos valores de glóbulos vermelhos (RBCs), concentração de hemoglobina (Hb), hematócrito (HCT) e glóbulos brancos (WBCs). Por outro lado, houve um aumento significativo na contagem de plaquetas. Além disso, o DS induziu uma deterioração renal; isso foi evidenciado pelo aumento significativo dos níveis séricos de ureia, creatinina, ácido úrico, Na, Ca, Mg e também do nível de óxido nítrico no tecido renal. Além disso, houve uma redução significativa nos níveis séricos de potássio (K) e glutationa reduzida (GSH) nos homogenatos renais. Além disso, os achados nos ratos tratados com DS + LE ou DS + FA mostraram uma proteção potencial sobre os marcadores hematológicos, estresse oxidativo no tecido renal e função renal perturbada pelo DS. LE e AF podem desempenhar um papel potente na prevenção do estresse hematológico adverso, do estresse oxidativo do tecido renal e da disfunção renal causada pelo DS por meio de seus fitoquímicos antioxidantes e bioativos.

Traffic speed prediction techniques in urban environments.

The present study developed Multiple Linear Regression (MLR) and machine learning (ML) models, including Artificial Neural Network (ANN), Support Vector Machine (SVM), and Random Forest (RF), to predict the mean free-flow speed (FFS) using several geometric, traffic, and pavement condition variables. The traffic features group includes spot speed, speed limit, average speed, 85th percentile speed, traffic and crossing pedestrian volumes, volume of exiting vehicles, percentage of elderly crossing pedestrians (Elderly%), percentage of heavy vehicles (HV%), and traffic calming measures (TCMs). The geometric characteristics include lateral clearance, number of effective lanes, number of access points (including median openings), road grade, effective lane width, and median width. The pavement condition category includes pavement roughness in the International Roughness Index (IRI). A total of 11 urban arterials were used to develop the MLR model and train the ML models. Test data were collected from two randomly selected roads to evaluate the performance of each model, investigate the differences between conventional linear regression and ML approaches, and determine the best prediction models based on the results of the two techniques. Results showed that the proposed ML algorithms outperformed linear regression models. They are believed to be valuable and strong tools to predict the mean FFS that adapts to sudden changes in traffic flow caused by exogenous conditions on urban arterials and can be employed in determining the most influential factors and building reliable prediction models where spot study is not feasible due to time and resource limitations.

Impact of baseline body mass index on the outcomes of patients with neuroendocrine neoplasms.

OBJECTIVE: To assess the impact of baseline body mass index (BMI) on the outcomes of patients with neuroendocrine neoplasms (NENs) in a population-based setting. METHODS: Linked provincial administrative databases (within the province of Alberta, Canada), 2004-2019, were accessed, and patients with NENs and complete information about BMI near the time of diagnosis were reviewed. The impact of BMI on overall survival was evaluated through the use of Kaplan-Meier survival estimates and multivariable Cox regression modeling. RESULTS: A total of 1010 patients with NENs and BMI information were included. Using Kaplan-Meier survival estimates, survival outcomes were best with individuals with obesity and were worst with underweight individuals (P < 0.0001). The following factors were associated with worse overall survival, older age (HR: 1.02; 95% CI: 1.01-1.03), male sex (HR: 1.60; 95% CI: 1.32-1.93), higher Charlson comorbidity index (HR: 1.22; 95% CI: 1.13-1.31), non-small intestinal primary (HR for gastric primary versus small intestinal primary: 2.36; 95% CI: 1.44-3.85), stage 4 disease (HR: 2.67; 95% CI: 2.16-3.31), neuroendocrine carcinoma histology (HR: 1.76; 95% CI: 1.43-2.17), and underweight BMI (HR versus normal BMI: 1.74; 95% CI: 1.11-2.73). When the model was repeated using BMI as a continuous variable (rather than as a categorical variable), increasing BMI was associated with better overall survival (HR with increasing BMI: 0.97; 95% CI: 0.95-0.98). CONCLUSIONS: Lower BMI is associated with worse overall survival among patients with NENs. This finding was demonstrable regardless of the tumor's stage or histology.

Revisiting the AJCC staging system of adrenocortical carcinoma.

OBJECTIVE: To evaluate the performance characteristics of AJCC 7th and 8th staging systems among patients with adrenal cortical carcinoma. METHODS: Surveillance, Epidemiology, and End Results (SEER) 18-registry was accessed and patients with adrenocortical carcinoma who were diagnosed 2010-2015 with complete information about AJCC 7th staging system were included. AJCC 8th staging system information was then reconstructed for each patient using available TNM staging variables. Kaplan-Meier overall survival estimates, multivariable Cox regression analysis, and concordance index (C-statistic) were used to examine the performance characteristics of both staging systems. RESULTS: A total of 574 patients with a diagnosis of adrenocortical carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, overall survival was compared among different AJCC stages for both versions; and the P value was significant (< 0.001) for both comparisons. C-statistic was then calculated for both staging systems and the results were as follows: for AJCC 7th version: 0.726 (95% CI 0.683-0.769); and for AJCC 8th version: 0.745 (95% CI 0.704-0.786). Patients with M1 disease (stage IV according to AJCC 8th edition) were then divided according to the extent of distant metastases into single versus multiple sites of metastases. Using Kaplan-Meier survival estimates, patients with a single site of metastases have better overall survival (P = 0.006). A C-statistic for a hypothetical modification of AJCC 8th staging system subdividing stage IV patients into IVA and IVB based on the number of metastatic sites was: 0.753 (95% CI 0.713-0.794). CONCLUSIONS: There is a minimal difference in the prognostic performance between both versions of the AJCC staging system. Subdivision of stage IV cancer into stage IVA and IVB (according to the number of organs with metastatic deposits) should be considered in subsequent versions of adrenocortical carcinoma staging.

Aqueous extract of bay leaf (Laurus nobilis) ameliorates testicular toxicity induced by aluminum chloride in rats.

Background and Aim: Human exposure to aluminum is inevitable, and one of the most adverse health effects of aluminum is a decrease in male fertility rates. Therefore, this study investigated the ameliorative effects of an aqueous extract from Laurus nobilis-bay leaf (BL) on aluminum chloride (AlCl3)-induced testicular toxicity in rats. Materials and Methods: Twenty-four Wistar rats were divided into four groups (n = 6, each group): The control (group 1) received normal saline; Group 2 animals were intraperitoneally administered with 30 mg/kg body weight (BW) AlCl3; and Groups 3 and 4 were co-administered AlCl3 with 125 or 250 mg/kg BW of BL extract, respectively, for 21 days. Testes, epididymis, and blood samples were collected. Testicular plasma enzyme activity was measured using a spectrophotometric assay, while concentrations of inflammatory biomarkers were determined using enzyme-linked immunosorbent assay kits. Results: There was a significant increase (p < 0.05) in testicular enzyme activity in the group treated with AlCl3. However, there was no significant (p > 0.05) difference in testicular enzyme activity in groups co-administered AlCl3 and BL extract as compared with that in control. There was a significant (p < 0.05) increase in testicular nitrite concentration in the AlCl3-treated group, whereas the administration of BL extract significantly (p < 0.05) decreased nitrite concentration in Groups 3 and 4. Furthermore, the administration of BL extracts increased sperm count and improved the morphology of the testes in AlCl3-treated rats. Flavonoids, phenolic compounds, alkaloids, tannin, glycosides, saponin, anthraquinones, and steroids were identified in BL extract, with alkaloids and glycosides being the most abundant. Conclusion: Aqueous extract from BL ameliorated the toxic effect of AlCl3 and exhibited anti-inflammatory properties by inhibiting nitrite production while improving sperm count and morphology in AlCl3-treated rats. The bioactivity of the extract may be attributed to the presence of a wide range of phytochemicals. Therefore, BL aqueous extract could be a promising source of novel compounds with male fertility-promoting and anti-inflammatory properties.

Diagnostic accuracy of flexible fiberoptic laryngoscopy: experience from a tertiary health institution in Nigeria.

BACKGROUND: Flexible fibreoptic laryngoscopy (FFL) is a technique of laryngeal visualization. The instrument (flexible laryngoscope) is relatively scarce in resource challenged countries. Where available, it is a useful compliment to the armamentarium of clinical tools at the disposal of the otolaryngologist. We evaluated the diagnostic value of flexible fibreoptic laryngoscope in a tertiary health institution in Nigeria. And we hypothesized that its diagnostic precision is comparable to direct laryngoscopy. METHODS: This is a retrospective study of records of 360 patients referred for FFL at the ENT clinic. Sensitivity and specificity of FFL for laryngeal lesions were determined using direct laryngoscopy (DL) as the gold standard. RESULTS: Of the 360 FFL reports studied, 336 additionally underwent DL. FFL findings in 311 (92.6%) cases were comparable with that of DL. FFL had a good detection rate for vocal cord palsy (sensitivity 100%, specificity 80.7%). Pick-up rate for vocal nodules, polyps, papillomatosis and palsy were statistically equal for FFL and DL (p value = 0.96). Diagnostic accuracy of FFL was good for supraglottic (sensitivity 100%, specificity 88.0%) and glottic (sensitivity 100%, specificity 92.3%) tumours; relatively lower for subglottic (sensitivity 83.3%; specificity 100%) and transglottic (sensitivity 80.0%, specificity 100%) tumours; and least for tumours involving more than on subsites (sensitivity 50%, specificity 100%). CONCLUSION: The sensitivity and specificity of FFL were not the same for all endo-laryngeal lesions; yet, the overall diagnostic accuracy of FFL is comparable with DL. Clinicians should be mindful of this variability to optimize its application.

Long lifetime of bialkali photocathodes operating in high gradient superconducting radio frequency gun.

High brightness, high charge electron beams are critical for a number of advanced accelerator applications. The initial emittance of the electron beam, which is determined by the mean transverse energy (MTE) and laser spot size, is one of the most important parameters determining the beam quality. The bialkali photocathodes illuminated by a visible laser have the advantages of high quantum efficiency (QE) and low MTE. Furthermore, Superconducting Radio Frequency (SRF) guns can operate in the continuous wave (CW) mode at high accelerating gradients, e.g. with significant reduction of the laser spot size at the photocathode. Combining the bialkali photocathode with the SRF gun enables generation of high charge, high brightness, and possibly high average current electron beams. However, integrating the high QE semiconductor photocathode into the SRF guns has been challenging. In this article, we report on the development of bialkali photocathodes for successful operation in the SRF gun with months-long lifetime while delivering CW beams with nano-coulomb charge per bunch. This achievement opens a new era for high charge, high brightness CW electron beams.

Subtype-specific risk factors for postmenopausal breast cancer: findings from the PLCO trial.

OBJECTIVE: The aim of this analysis is to evaluate the relative weight of different epidemiological risk factors on the development of different breast cancer subtypes (i.e. luminal, Her2+ overexpressed or triple negative). METHODS: De-identified datasets of female participants recruited within the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial were accessed. Multivariate Cox regression analysis was utilized to assess factors affecting the development of breast cancer (regardless of subtype). Additional multivariate analyses were conducted to assess factors affecting the development of the three principal subtypes of breast cancer (ER+/Her2- breast cancer; Her2 overexpressed breast cancer and ER-/Her2- breast cancer). RESULTS: A total of 73,570 eligible participants were evaluated in the current analysis of which 2370 participants subsequently developed breast cancer. The following factors were associated with a higher risk of ER+/Her2- breast cancer: white race (P < 0.001), nulliparity (P < 0.001), higher body mass index (P = 0.003), prior exposure to hormone treatment (P = 0.004) and breast cancer in first-degree female relatives (P < 0.001). The following factors were associated with a higher risk of Her2 overexpressed breast cancer: prior exposure to hormone treatment (P = 0.002) and breast cancer in first-degree female relatives (P = 0.001). The following factors were associated with a higher risk of ER-/Her2- breast cancer: black race (P = 0.013), younger age (P = 0.017) and breast cancer in first-degree female relatives (P 0.023). CONCLUSIONS: There is considerable heterogeneity in risk factors among patients with different subtypes of breast cancer. In particular, factors associated with high estrogen levels seem to be associated with luminal breast cancer rather than other breast cancer subtypes.

Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study

BACKGROUND: To our knowledge, no previous study has prospectively documented the incidence of common diseases and related mortality in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) with standardised approaches. Such information is key to developing global and context-specific health strategies. In our analysis of the Prospective Urban Rural Epidemiology (PURE) study, we aimed to evaluate differences in the incidence of common diseases, related hospital admissions, and related mortality in a large contemporary cohort of adults from 21 HICs, MICs, and LICs across five continents by use of standardised approaches. METHODS: The PURE study is a prospective, population-based cohort study of individuals aged 35-70 years who have been enrolled from 21 countries across five continents. The key outcomes were the incidence of fatal and non-fatal cardiovascular diseases, cancers, injuries, respiratory diseases, and hospital admissions, and we calculated the age-standardised and sex-standardised incidence of these events per 1000 person-years. FINDINGS: This analysis assesses the incidence of events in 162 534 participants who were enrolled in the first two phases of the PURE core study, between Jan 6, 2005, and Dec 4, 2016, and who were assessed for a median of 9·5 years (IQR 8·5-10·9). During follow-up, 11 307 (7·0%) participants died, 9329 (5·7%) participants had cardiovascular disease, 5151 (3·2%) participants had a cancer, 4386 (2·7%) participants had injuries requiring hospital admission, 2911 (1·8%) participants had pneumonia, and 1830 (1·1%) participants had chronic obstructive pulmonary disease (COPD). Cardiovascular disease occurred more often in LICs (7·1 cases per 1000 person-years) and in MICs (6·8 cases per 1000 person-years) than in HICs (4·3 cases per 1000 person-years). However, incident cancers, injuries, COPD, and pneumonia were most common in HICs and least common in LICs. Overall mortality rates in LICs (13·3 deaths per 1000 person-years) were double those in MICs (6·9 deaths per 1000 person-years) and four times higher than in HICs (3·4 deaths per 1000 person-years). This pattern of the highest mortality in LICs and the lowest in HICs was observed for all causes of death except cancer, where mortality was similar across country income levels. Cardiovascular disease was the most common cause of deaths overall (40%) but accounted for only 23% of deaths in HICs (vs 41% in MICs and 43% in LICs), despite more cardiovascular disease risk factors (as judged by INTERHEART risk scores) in HICs and the fewest such risk factors in LICs. The ratio of deaths from cardiovascular disease to those from cancer was 0·4 in HICs, 1·3 in MICs, and 3·0 in LICs, and four upper-MICs (Argentina, Chile, Turkey, and Poland) showed ratios similar to the HICs. Rates of first hospital admission and cardiovascular disease medication use were lowest in LICs and highest in HICs. INTERPRETATION: Among adults aged 35-70 years, cardiovascular disease is the major cause of mortality globally. However, in HICs and some upper-MICs, deaths from cancer are now more common than those from cardiovascular disease, indicating a transition in the predominant causes of deaths in middle-age. As cardiovascular disease decreases in many countries, mortality from cancer will probably become the leading cause of death. The high mortality in poorer countries is not related to risk factors, but it might be related to poorer access to health care. (AU)

Outcomes of metastatic colorectal cancer patients in relationship to prior and concurrent antibiotics use; individual patient data analysis of three clinical trials.

BACKGROUND: Antibiotic use at the time of chemotherapy has been linked with inferior outcomes among a number of solid tumors. The current study aims at further assessing this observation among metastatic colorectal cancer patients treated with first-line systemic chemotherapy. METHODS: This is a pooled analysis of three clinical trial datasets (NCT00384176; NCT00272051; NCT00305188) that were accessed from the Project Data Sphere platform. Kaplan-Meier survival estimates were used to evaluate the impact of antibiotic use on overall and progression-free survival and multivariable Cox regression models were employed to further assess this impact. RESULTS: A total of 1446 patients were included in the current analysis. These include 108 patients who received antibiotics before the start of chemotherapy, 499 patients who received antibiotics after the start of chemotherapy, and 839 patients who did not receive antibiotics. Using Kaplan-Meier survival estimates, the use of antibiotics prior to the start of chemotherapy was associated with worse progression-free (P = 0.001) and overall survival (P < 0.001). Likewise, when multivariable Cox regression analyses were conducted, prior antibiotic use is associated with worse progression-free (HR for antibiotic use during chemotherapy versus antibiotic use prior to chemotherapy = 0.764; 95% CI 0.604-0.966; P = 0.024) and overall survival (HR for antibiotic use during chemotherapy versus antibiotic use prior to chemotherapy = 0.710; 95% CI 0.537-0.940; P = 0.017). CONCLUSION: Antibiotic use before (but not following) the start of 5FU-based chemotherapy is associated with worse progression-free and overall survival among patients with metastatic colorectal cancer.

Prognostic value of HPV status among patients with hypopharyngeal carcinoma: a population-based study.

OBJECTIVE: To clarify the prognostic role of human papilloma virus (HPV) status among patients with hypopharyngeal carcinoma. METHODS: Surveillance, Epidemiology and End Results (SEER) HPV head and neck cancer database has been accessed and cases with hypopharyngeal squamous cell carcinoma with known HPV status were retrieved. Kaplan-Meier survival estimates were used to evaluate the impact of HPV status on overall survival outcomes of included patients and multivariable cox regression analysis was used to assess the impact of HPV status on overall and head and neck cancer-specific survival. RESULTS: A total of 1157 patients' records with hypopharyngeal carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, patients with HPV positive status seem to have better overall survival compared to patients with HPV negative status (P < 0.01). When stratified by stage, patients with HPV positive regional and distant disease have better overall survival compared to patients with HPV negative regional and distant disease (P < 0.01 for both categories). The same observation cannot be confirmed for patients with localized disease (P = 0.15). Using multivariable Cox regression analysis, HPV positive status seems to be associated with better overall survival (HR for HPV negative versus HPV positive status: 1.76; 95% CI 1.39-2.24; P < 0.01) and cancer-specific survival (HR for HPV negative versus HPV positive status: 1.54; 95% CI 1.12-2.11; P < 0.01). CONCLUSIONS: Patients with HPV positive hypopharyngeal carcinoma seem to have better overall and cancer-specific survival compared to patients with HPV negative hypopharyngeal carcinoma.

Deposition of Multiscale Thickness Graphene Coating by Harnessing Extreme Heat and Rapid Quenching: Toward Commercialization.

Deposition of graphene as a coating material over large-scale areas is an intense topic of research because of complexities involved in the existing deposition techniques. Higher defects and compromised properties restricted in realizing the full potential of graphene coating. This work aims to deposit graphene coatings by adopting a traditional technique, that is, plasma spraying, which has inherent merits of extremely high cooling rate (∼106 K/s) and low plasma exposure time (∼0.1-10 µs). Graphene nanoplatelets (GNPs) were spray-dried into spherical agglomerates (∼60 µm dia.) and coatings were deposited over a wide range of surfaces. Continuous monitoring of temperature and velocity of in-flight GNPs was done using a diagnostic sensor. Deposition of GNP coatings was the result of striking of quasi-2D melted GNPs with higher velocity (∼197 m/s) toward the substrate. Postcharacterizations confirmed that GNPs did not collapse even after being exposed to harsh environments in plasma. Instead, high temperatures proved to be beneficial in purifying the commercial GNPs. The coatings were transparent even in the short-wavelength infrared region and remained electrically conductive. A proof-of-concept was established by carrying out preliminary corrosion and antifriction tests. Outstanding reduction of ∼3.5 times in corrosion rate and 3 times in coefficient of friction was observed in GNP-deposited coating. It is envisaged that graphene coating by plasma spraying can bring a revolution in commercial sectors.

Generalisability of Common Oncology Clinical Trial Eligibility Criteria in the Real World.

AIMS: Strict oncology clinical trial eligibility criteria can contribute to low accrual and result in poorly generalisable study findings. Using common eligibility criteria, we sought to (i) determine how many patients would be eligible versus ineligible and (ii) describe real-world patterns of treatments and outcomes between those considered trial eligible and ineligible. MATERIALS AND METHODS: The Alberta Cancer Registry was used to assemble a population-based cohort of patients diagnosed with 11 common malignancies between 2004 and 2015. We considered age >75 years, anaemia, comorbid conditions (heart disease, uncontrolled diabetes, kidney disease, liver disease) and history of a prior malignancy or immunosuppression to be exclusion criteria. Logistic regression was used to characterise the likelihood of receiving treatment. Cox regression models were constructed to determine cancer-specific and overall survival. RESULTS: We identified 125 316 cancer patients, of whom 53% were men; the median age was 66 (interquartile range 48-84) years. Approximately 38% of patients were considered trial ineligible. The most common reasons for ineligibility were advanced age (24%) and heart disease (16%). In this ineligible group, 12, 47 and 19% still underwent chemotherapy, surgery and radiotherapy, respectively. Compared with ineligible patients, eligible patients were more likely to undergo chemotherapy (odds ratio 1.98, 95% confidence interval 1.89-2.07, P < 0.0001), surgery (odds ratio 1.39, 95% confidence interval 1.32-1.46, P < 0.0001) and radiotherapy (odds ratio 1.46, 95% confidence interval 1.4-1.52, P < 0.0001). Compared with ineligible patients who did not receive treatment, those considered ineligible but who still received treatment experienced improved cancer-specific survival (hazard ratio 0.75, 95% confidence interval 0.74-0.77, P < 0.0001) and overall survival (hazard ratio 0.89, 95% confidence interval 0.87-0.90, P < 0.0001). CONCLUSIONS: A significant proportion of real-world patients are unable to participate in clinical trials due to stringent exclusion criteria, but many still receive treatment in routine practice. The eligibility criteria of oncology clinical trials should be broadened.

Outcomes of clinically localized prostate cancer patients managed with initial monitoring approach versus upfront local treatment: a North American population-based study.

OBJECTIVE: To assess the outcomes of active monitoring (active surveillance or watchful waiting) as an initial management approach compared to upfront definitive local treatments (prostatectomy or radiation therapy) in a cohort of clinically localized prostate cancer patients. METHODS: Patients with clinically localized prostate cancer registered within the Surveillance, Epidemiology and End Results (SEER) watchful waiting database from 2010-2015 were reviewed. Kaplan-Meier analysis was used to compare overall survival outcomes between patients treated with different initial therapeutic approaches. Multivariate Cox regression analysis (stratified by the risk group) was used to assess potential factors affecting prostate cancer-specific survival. RESULTS: Using Kaplan-Meier analysis, prostatectomy was associated with better overall survival compared to radiation therapy and active monitoring (P < 0.001). Multivariate Cox regression analysis was then employed to evaluate different factors affecting prostate cancer-specific survival. Among patients with low-risk disease, the following factors were predictive of better prostate cancer-specific survival: younger age (hazard ratio for patients ≥ 70 years versus patients 40-69 years: 2.081; 95% CI 1.277-3.390; P = 0.003), white race (hazard ratio for black race versus white race: 2.575; 95% CI 1.538-4.311; P < 0.001), non-Hispanic ethnicity (hazard ratio versus Hispanic ethnicity: 0.472; 95% CI 0.244-0.910; P = 0.025), and initial treatment with prostatectomy (hazard ratio for prostatectomy versus active monitoring: 0.551; 95% CI 0.371-0.818; P = 0.003). CONCLUSIONS: Active monitoring seems to be at least as effective as upfront radiation therapy in the management of low-risk disease. Radical prostatectomy is associated with better overall and prostate cancer-specific survival compared to either radiation therapy or active monitoring.

Instant Tuning of Superhydrophilic to Robust Superhydrophobic and Self-Cleaning Metallic Coating: Simple, Direct, One-Step, and Scalable Technique.

We present a simple, direct, one-step, scalable technique for instant tuning of all the different states of wetting characteristics using atmospheric plasma spray (APS) technique. We observed that, just by changing the process parameters in the APS technique, the wetting characteristics of an intrinsically hydrophilic aluminum metallic surface can be tuned to superhydrophilic (contact angle (CA): 0°), hydrophilic (CA: 19.6°), hydrophobic (CA: 97.6°), and superhydrophobic (CA: 156.5°) surfaces. Also, tuned superhydrophobic surface showed an excellent self-cleaning property. Further, we demonstrated that these surfaces retain their superhydrophobic nature even after exposure at elevated temperatures (up to 773 K) and on application of mechanical abrasion. Manipulation in different wetting behavior was possible mainly due to the presence of varying degrees of smooth surface as well as micropillars, which incorporated the multiscale roughness to the surface. "Re-entrant"-like microstructures such as mushroom, cauliflower, and cornet microstructures were observed in the case of tuned superhydrophobic surface, which is well-known for achieving the excellent water repellency over the hydrophilic surface.

Impact of diabetes comorbidity on the efficacy and safety of FOLFOX first-line chemotherapy among patients with metastatic colorectal cancer: a pooled analysis of two phase-III studies.

BACKGROUND: The current analysis aims to provide an evaluation of the impact of diabetes mellitus (DM) on the efficacy and safety of first-line FOLFOX chemotherapy for patients with metastatic colorectal cancer (mCRC). METHODS: This is a pooled analysis of the comparator arms of two clinical trials (NCT00272051; NCT00305188) which evaluated first-line FOLFOX chemotherapy for patients with mCRC. The overall survival and progression-free survival according to patient subsets (non-diabetic and diabetic patients) were assessed through Kaplan-Meier analysis and log-rank testing. Propensity score matching was additionally conducted to account for heterogeneity in baseline characteristics of different subsets of patients. RESULTS: A total of 756 patients were enrolled in the current analysis; of which 64 patients have pre-existing DM while 692 patients were non-diabetic. Through Kaplan-Meier analysis, no evidence for overall or progression-free survival difference was found among the two patient subsets (P = 0.501; P = 0.960, respectively). Moreover, metformin treatment does not affect overall or progression-free survival among diabetic patients (P = 0.598; P = 0.748, respectively). Repetition of overall and progression-free survival assessment following propensity score matching does not reveal any differences. Comparing diabetic to non-diabetic patients, there were no differences between the two groups in terms of acute oxaliplatin-induced neurological symptoms including cold-induced dysthesia (P = 0.600), laryngeal dysthesia (P = 0.707), jaw pain (P = 0.743) or muscle pain (P = 0.506). Moreover, no difference was seen between the two groups in terms of the incidence of long-term oxaliplatin-induced paresthesia (P = 0.107), highest grade of paresthesia (P = 0.498) or rates of recovery from paresthesia (P = 0.268). Diabetic patients have, however, a shorter time to develop oxaliplatin-induced paresthesia (P = 0.024). CONCLUSION: DM does not seem to affect overall or progression-free survival of mCRC patients treated with first-line FOLFOX chemotherapy. Moreover, DM does not influence the incidence or severity of oxaliplatin-induced paresthesia in those patients while it might lead to a shorter time to develop oxaliplatin-induced paresthesia compared to non-diabetic patients.

Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies.

BACKGROUND: The current analysis aims to evaluate the impact of statin co-treatment on the survival of patients with metastatic pancreatic cancer. METHODS: This is a pooled analysis of de-identified patient data from two clinical trials (NCT01124786; NCT00844649). Overall and progression-free survival according to patient subsets (patients who received or who did not receive statins) were assessed through Kaplan-Meier analysis and log-rank test. Univariate and multivariate Cox regression analysis was performed to evaluate different factors potentially affecting overall and progression-free survival. Propensity score matching was performed to address heterogeneity in baseline characteristics of different subgroups of patients. RESULTS: A total of 797 patients were assessed in the current study; of which 156 patients received statins and 641 did not receive statins. Using Kaplan-Meier survival estimates, patients who received statins seem to have better overall and progression-free survival compared to patients who did not (P = 0.008; P < 0.001, respectively). In multivariate analysis for factors affecting overall survival, the following factors were associated with worse overall survival: worse performance status (P < 0.001), no statin use (P = 0.044) and multiple sites of metastatic disease (P = 0.023); likewise in multivariate analysis for factors affecting progression-free survival, the following factors were associated with worse progression-free survival: worse performance status (P < 0.001), gemcitabine elaidate chemotherapy (P = 0.015) and no statin use (P = 0.048). Following propensity score matching and using Kaplan-Meier estimates, statin use was also associated with better overall and progression-free survival (P = 0.005; P = 0.040, respectively). CONCLUSION: Statin use seems to be associated with better overall survival among patients with metastatic pancreatic cancer treated with first-line chemotherapy. Prospective studies designed specifically to assess this potential effect of statins are needed.

Outcomes of early-stage breast cancer patients treated with sequential anthracyclines-taxanes in relationship to relative dosing intensity: a secondary analysis of a randomized controlled trial.

PURPOSE: To assess the impact of relative dosing intensity (RDI) on the outcomes of breast cancer patients referred for adjuvant anthracycline-taxane chemotherapy. METHODS: This is a secondary analysis of the outcomes of patients in the comparator arm of the BCIRG005 study who received adjuvant adriamycin/cyclophosphamide (AC)-docetaxel regimen. Overall survival was assessed according to RDI through Kaplan-Meier analysis. Univariate and multivariate analyses of parameters affecting overall survival were then conducted through Cox regression analysis. RESULTS: Kaplan-Meier analysis of overall survival according to RDI for the AC-docetaxel regimen (< 90 vs. ≥ 90%) was conducted and it showed that RDI < 90% is associated with worse overall survival (P = 0.006). In univariate Cox regression analysis, the following parameters significantly affected overall survival (P < 0.05): age, T stage, lymph node ratio, hormone receptor status, and grade of the disease and RDI for AC-docetaxel regimen. When these factors were included in multivariate analysis, the following factors were associated with worse overall survival: age less than 40 years (P < 0.0001), greater T stage (P < 0.0001), greater lymph node ratio (P < 0.0001), negative hormone receptor status (P = 0.001), high grade (P < 0.0001) and RDI ≤ 90% (P = 0.015). Formal interaction testing between RDI and hormone receptor status has a non-significant P value (P = 0.794). CONCLUSION: Lower RDI for the whole anthracycline-taxane protocol is associated with worse patient survival. Every effort should be exercised to avoid unnecessary dose reductions and/or interruptions among early breast cancer patients receiving adjuvant anthracycline-taxane chemotherapy.