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.

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.

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.

A New Green Ionic Liquid-Based Corrosion Inhibitor for Steel in Acidic Environments.

This work examines the use of new hydrophobic ionic liquid derivatives, namely octadecylammonium tosylate (ODA-TS) and oleylammonium tosylate (OA-TS) for corrosion protection of steel in 1 M hydrochloric acid solution. Their chemical structures were determined from NMR analyses. The surface activity characteristics of the prepared ODA-TS and OA-TS were evaluated from conductance, surface tension and contact angle measurements. The data indicate the presence of a double bond in the chemical structure of OA-TS modified its surface activity parameters. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) measurements, scanning electron microscope (SEM), Energy dispersive X-rays (EDX) analysis and contact angle measurements were utilized to investigate the corrosion protection performance of ODA-TS and OA-TS on steel in acidic solution. The OA-TS and ODA-TS compounds showed good protection performance in acidic chloride solution due to formation of an inhibitive film on the steel surface.

Genotypes of hepatitis C virus infection in Bangladeshi population.

Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide also in Bangladesh. Prevalence of Hepatitis C virus infection in rural adult population of Bangladesh is reported to be 0.6% but the exact pattern of existing genotype has not been well studied. Genotyping of HCV is important for the planning of treatment duration and predicting the response to treatment in HCV infection. This study was done to identify the existing HCV genotypes in the diagnosed cases of chronic hepatitis C infection in Bangladesh. This study was a prospective as well as retrospective cross-sectional observational study done in the department of Gastroenterology of Bangabandhu Sheikh Mujib Medical University, Dhaka Bangladesh. Cases were also taken from department of Hepatology of Bangabandhu Sheikh Mujib Medical University and Square General Hospital, Dhaka. The study was from January 2010 to March 2011. In total, 417 patients having chronic HCV confirmed by positive anti-HCV and HCV-RNA tests attending to above mentioned institutions were included in this study. Out of the 417 study subjects, 303 were males (72.66%) and 114 (27.34%) were females between 05 to 78 years of age. Most cases were in the age group 30-50 years (57.06%). The study showed that 209 (50.19%) were infected with Genotype 3. Next common identified genotype of HCV was a combination of type 3 & 4, which accounted for 120 (28.77%) and genotype -1 represented 59 (14.14%) of the cases. Other less common identified genotypes were 2, 4, 5 and mixed genotypes -1 & 3, 5 & 6 and 2 & 3; the figure being 12(2.87%), 8(1.91%), 1(0.23%), 5(1.19%), 2(0.47%) and 1(0.23%) respectively. Several subtypes were also found. Genotype 3 was the commonest HCV genotype among the Bangladeshi population. Different HCV genotypes will give a good idea regarding the plan of treatment and possible response rate as well as prognosis of HCV infection in Bangladesh. This study had some limitation like relatively smaller sample size and shorter period for the study. Further studies over a larger population are needed to draw any conclusive opinion.

Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.

BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. METHODS: We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). RESULTS AND CONCLUSIONS: Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.

Hexagonal graphene onion rings.

Precise spatial control of materials is the key capability of engineering their optical, electronic, and mechanical properties. However, growth of graphene on Cu was revealed to be seed-induced two-dimensional (2D) growth, limiting the synthesis of complex graphene spatial structures. In this research, we report the growth of onion ring like three-dimensional (3D) graphene structures, which are comprised of concentric one-dimensional hexagonal graphene ribbon rings grown under 2D single-crystal monolayer graphene domains. The ring formation arises from the hydrogenation-induced edge nucleation and 3D growth of a new graphene layer on the edge and under the previous one, as supported by first principles calculations. This work reveals a new graphene-nucleation mechanism and could also offer impetus for the design of new 3D spatial structures of graphene or other 2D layered materials. Additionally, in this research, two special features of this new 3D graphene structure were demonstrated, including nanoribbon fabrication and potential use in lithium storage upon scaling.

Whole-genome copy number variation analysis in anophthalmia and microphthalmia.

Anophthalmia/microphthalmia (A/M) represent severe developmental ocular malformations. Currently, mutations in known genes explain less than 40% of A/M cases. We performed whole-genome copy number variation analysis in 60 patients affected with isolated or syndromic A/M. Pathogenic deletions of 3q26 (SOX2) were identified in four independent patients with syndromic microphthalmia. Other variants of interest included regions with a known role in human disease (likely pathogenic) as well as novel rearrangements (uncertain significance). A 2.2-Mb duplication of 3q29 in a patient with non-syndromic anophthalmia and an 877-kb duplication of 11p13 (PAX6) and a 1.4-Mb deletion of 17q11.2 (NF1) in two independent probands with syndromic microphthalmia and other ocular defects were identified; while ocular anomalies have been previously associated with 3q29 duplications, PAX6 duplications, and NF1 mutations in some cases, the ocular phenotypes observed here are more severe than previously reported. Three novel regions of possible interest included a 2q14.2 duplication which cosegregated with microphthalmia/microcornea and congenital cataracts in one family, and 2q21 and 15q26 duplications in two additional cases; each of these regions contains genes that are active during vertebrate ocular development. Overall, this study identified causative copy number mutations and regions with a possible role in ocular disease in 17% of A/M cases.

Combination trans arterial chemoembolization (TACE) plus sorafenib for the management of unresectable hepatocellular carcinoma: a systematic review of the literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver neoplasm and the fifth most common cancer worldwide. Intermediate stage HCC [traditionally defined as Barcelona Clinic Liver Cancer (BCLC) B disease and traditionally treated with trans arterial chemoembolization (TACE)] and advanced stage HCC (traditionally defined as BCLC C disease and traditionally treated with sorafenib) are two distinct disease entities with rapidly evolving multimodality treatment approaches. In this systematic review we explore the evidence surrounding the value of using a TACE/sorafenib combination in these two subsets of HCC. METHODS: PubMed, Medline, the Cochrane Library, EMBASE and Google Scholar were searched using the terms "HCC" OR "Hepatoma" or "Liver cancer" AND "TACE" OR "Chemoembolization" AND "Sorafenib" and specifying only English literature. Outcomes of interest included time to progression and overall survival (TTP and OS), tumor response, and toxicities. RESULTS: A total of 17 potentially relevant trials were identified, of which six studies were excluded. Hence, 11 trials involving 1,000 patients were included, encompassing two phase 1 studies, one phase 3 study, two retrospective analyses and six phase 2 studies. Median TTP was reported in five out of 11 studies and it ranged from 6.3 to 9.0 months. Median OS was reported in five out of 11 studies and it was similarly variable as PFS, ranging from 12 to 29 months. The DCR (disease control rate) was reported in eight out of 11 studies, ranging from 32 to 95%. Frequently reported grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase, fatigue, hypertension, hand-foot skin reaction and diarrhea. CONCLUSIONS: The sorafenib/TACE combination shows promise as an effective and tolerable treatment strategy for intermediate stage/advanced HCC. The reported efficacy of a sorafenib/TACE combination appears to compare favorably with sorafenib or TACE monotherapies, the most commonly implemented strategies for unresectable HCC. Further clinical studies are warranted to accurately determine which patients are expected to benefit most from such combination strategies.

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.

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.

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.

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.

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.

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.

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.

Phenotypic variation in Streptomyces sp. DSM 40537, a lipoteichoic acid producing actinomycete.

AIMS: To reinvestigate the production of lipoteichoic acid (LTA) by the actinomycete strain Streptomyces sp. DSM 40537 (=ATCC 3351). METHODS AND RESULTS: LTA was extracted and purified from strain Streptomyces sp. DSM 40537. The identification of the LTA was confirmed by Western blotting with a monoclonal antibody. During these studies, two stable phenotypic variants of DSM 40537 were obtained, one of which released a distinctive orange pigment. 16S rRNA gene sequencing of each variant yielded identical sequences and allowed phylogenetic analysis to be performed. CONCLUSIONS: Streptomyces sp. DSM 40537 was shown to exhibit stable morphological variation. The strain was confirmed to be a LTA-producing actinomycete and to belong to the Streptomyces albidoflavus cluster within the genus Streptomyces. SIGNIFICANCE AND IMPACT OF THE STUDY: These data provide important support for the hypothesis that the distribution of LTA is linked to that of wall teichoic acids and emphasizes the need to reinvestigate LTA distribution in actinomycetes.

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.

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.