Showing papers by "Nan Lin published in 2014"
TL;DR: Her2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis.
Abstract: Purpose To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) –positive advanced breast cancer. Methods The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival (PFS), and adverse events. Results A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and PFS benefits for docetaxel, trastuzumab, and pertuzumab in first-line treatment, and the EMILIA trial found survival and PFS benefits for trastuzumab emtansine (T-DM1) in second-line treatment. T-DM1 also showed a third-line PFS benefit. One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive ...
317 citations
TL;DR: Although total emissions are still increasing in developing countries, their intensities in terms of gross domestic production or energy consumption have decreased and their estimates for developing countries are higher than those previously reported.
Abstract: Emission quantification of primary particulate matter (PM) is essential for assessment of its related climate and health impacts. To reduce uncertainty associated with global emissions of PM2.5, PM10, and TSP, we compiled data with high spatial (0.1° × 0.1°) and sectorial (77 primary sources) resolutions for 2007 based on a newly released global fuel data product (PKU-FUEL-2007) and an emission factor database. Our estimates for developing countries are higher than those previously reported. Spatial bias associated with large countries could be reduced by using subnational fuel consumption data. Additionally, we looked at temporal trends from 1960 to 2009 at country-scale resolution. Although total emissions are still increasing in developing countries, their intensities in terms of gross domestic production or energy consumption have decreased. PM emitted in developed countries is finer owing to a larger contribution from nonindustrial sources and use of abatement technologies. In contrast, countries like China, with strong industry emissions and limited abatement facilities, emit coarser PM. The health impacts of PM are intensified in hotspots and cities owing to covariance of sources and receptors. Although urbanization reduces the per person emission, overall health impacts related to these emissions are heightened because of aggregation effects.
212 citations
TL;DR: Women with T1a,b tumors have an excellent prognosis without chemotherapy and represent an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks.
Abstract: Purpose Treatment decisions for patients with T1a,bN0M0 breast cancer are challenging. We studied the time trends in use of adjuvant chemotherapy and survival outcomes among these patients. Patients and Methods This was a prospective cohort study within the National Comprehensive Cancer Network Database that included 4,113 women with T1a,bN0M0 breast cancer treated between 2000 and 2009. Tumors were grouped by size (T1a, T1b), biologic subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and receipt of chemotherapy with or without trastuzumab. Results Median follow-up time was 5.5 years. Eight percent of patients with HR-positive/HER2-negative tumors were treated with chemotherapy. Fifty-two percent of those with HER2-positive or HR-negative/HER2-negative breast cancers received chemotherapy, with an increase over the last decade. Survival outcomes diverged by subtype and size, but the 5-year distant relapse-free survival (DRFS) did not exceed 10% in any sub...
192 citations
TL;DR: Clinicians should not perform routine magnetic resonance imaging to screen for brain metastases, but rather should have a low threshold for MRI of the brain because of the high incidence of brain metastase among patients with HER2-positive advanced breast cancer.
Abstract: Purpose To provide formal expert consensus- based recommendations to practicing oncologists and others on the management of brain metastases for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer. Methods The American Society of Clinical Oncology (ASCO) convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic review of the literature. When that failed to yield sufficiently strong quality evidence, the Expert Panel undertook a formal expert consensus- based process to produce these recommendations. ASCO used a modified Delphi process. The panel members drafted recommendations, and a group of other experts joined them for two rounds of formal ratings of the recommendations.
159 citations
TL;DR: The association between low anesthetic concentration and delirium is a surprising finding and could reflect that patients with poor health are both more sensitive to the effects of volatile anesthetic drugs and are also more likely to develop postoperativeDelirium.
Abstract: Background
Postoperative delirium in the intensive care unit (ICU) is a frequent complication after cardiac or thoracic surgery and is associated with increased morbidity and mortality.
153 citations
TL;DR: Global BC emissions from 1960 to 2007 were estimated for 64 sources, by using recompiled fuel consumption and emission factor data sets, to find that the BC emission intensity had decreased for all the regions, especially China and India.
Abstract: Black carbon (BC) plays an important role in both climate change and health impact. Still, BC emissions as well as the historical trends are associated with high uncertainties in existing inventories. In the present study, global BC emissions from 1960 to 2007 were estimated for 64 sources, by using recompiled fuel consumption and emission factor data sets. Annual BC emissions had increased from 5.3 (3.4–8.5 as an interquartile range) to 9.1 (5.6–14.4) teragrams during this period. Our estimations are 11–16% higher than those in previous inventories. Over the period, we found that the BC emission intensity, defined as the amount of BC emitted per unit of energy production, had decreased for all the regions, especially China and India. Improvements in combustion technology and changes in fuel composition had led to an increase in energy use efficiency, and subsequently a decline of BC emission intensities in power plants, the residential sector, and transportation. On the other hand, the BC emission intens...
126 citations
Harvard University1, Memorial Sloan Kettering Cancer Center2, Cleveland Clinic3, Mayo Clinic4, University of Turin5, University of Western Ontario6, University of Washington7, University of Toronto8, University of Zurich9, University of California, Los Angeles10, Columbia University11, Ludwig Maximilian University of Munich12, Erasmus University Rotterdam13
TL;DR: The NANO scale is designed to combine with radiographic assessment to provide an overall assessment of outcome for neuro-oncology patients in clinical trials and in daily practice and complements existing patient-reported outcomes and cognition testing to combine for a global clinical outcome assessment of well-being among brain tumor patients.
Abstract: BACKGROUND: The Macdonald criteria and RANO criteria define radiologic parameters to classify therapeutic outcome among malignant glioma patients. While both scales specify that clinical status must be incorporated for overall assessment, neither provides specific parameters to do so. Furthermore, both scales prioritize clinical status over radiology in that response requires at least stable clinical status, while clinical deterioration is sufficient to declare progression. We hypothesized that a standardized metric to measure neurologic function will permit better overall response assessment in neuro-oncology. METHODS: An international group of neuro-oncologists convened bi- weekly for the past year to draft the Neurologic Assessment in Neuro-Oncology (NANO) criteria as an objective and quantifiable metric of neurologic function evaluable during a routine office examination. RESULTS: The NANO scale is a quick, clinician-friendly, and quantifiable evaluation of eight relevant neurologic domains based on direct observation/testing conducted during routine office visits. The score defines criteria for domain-specific and overall scores of response, progression, stable disease and not assessed. A given domain will be scored non-evaluable if it cannot be accurately assessed due to pre-existing conditions, co-morbid events, and/or concurrent medications. CONCLUSION: The NANO criteria aims to provide a more detailed and objective measure of neurologic function than currently exists. These criteria are designed to enable a consistent evaluation of neurologic function which will facilitate comparisons across clinical trials and therapeutic interventions. Implementation and validation of these criteria are planned, and future modifications are anticipated for further optimization.
122 citations
TL;DR: Patients' tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge.
Abstract: Accurate self-awareness is essential for adapting one's tasks and goals to one's actual abilities. Patients with neurodegenerative diseases, particularly those with right frontal involvement, often present with poor self-awareness of their functional limitations that may exacerbate their already jeopardized decision-making and behaviour. We studied the structural neuroanatomical basis for impaired self-awareness among patients with neurodegenerative disease and healthy older adults. One hundred and twenty-four participants (78 patients with neurodegenerative diseases including Alzheimer's disease, behavioural variant frontotemporal dementia, right-temporal frontotemporal dementia, semantic variant and non-fluent variant primary progressive aphasia, and 46 healthy controls) described themselves on the Patient Competency Rating Scale, rating observable functioning across four domains (daily living activities, cognitive, emotional control, interpersonal). All participants underwent structural magnetic resonance imaging. Informants also described subjects' functioning on the same scale. Self-awareness was measured by comparing self and informant ratings. Group differences in discrepancy scores were analysed using general linear models, controlling for age, sex and disease severity. Compared with controls, patients with behavioural variant frontotemporal dementia overestimated their functioning in all domains, patients with Alzheimer's disease overestimated cognitive and emotional functioning, patients with right-temporal frontotemporal dementia overestimated interpersonal functioning, and patients with non-fluent aphasia overestimated emotional and interpersonal functioning. Patients with semantic variant aphasia did not overestimate functioning on any domain. To examine the neuroanatomic correlates of impaired self-awareness, discrepancy scores were correlated with brain volume using voxel-based morphometry. To identify the unique neural correlates of overlooking versus exaggerating deficits, overestimation and underestimation scores were analysed separately, controlling for age, sex, total intracranial volume and extent of actual functional decline. Atrophy related to overestimating one's functioning included bilateral, right greater than left frontal and subcortical regions, including dorsal superior and middle frontal gyri, lateral and medial orbitofrontal gyri, right anterior insula, putamen, thalamus, and caudate, and midbrain and pons. Thus, our patients' tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge. The anatomic correlates of underestimation (right rostral anterior cingulate cortex, uncorrected significance level) were distinct from overestimation and had a substantially smaller effect size. This suggests that underestimation or 'tarnishing' may be influenced by non-structural neurobiological and sociocultural factors, and should not be considered to be on a continuum with overestimation or 'polishing' of functional capacity, which appears to be more directly mediated by neural circuit dysfunction.
102 citations
TL;DR: Results in culture and in mice provide support for a readily implemented strategy by which the heterogeneity and evolvability of metastatic ER+ breast tumors, and perhaps other advanced cancers, might be controlled and provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics.
Abstract: The efficacy of hormonal therapies for advanced estrogen receptor-positive breast cancers is limited by the nearly inevitable development of acquired resistance. Efforts to block the emergence of resistance have met with limited success, largely because the mechanisms underlying it are so varied and complex. Here, we investigate a new strategy aimed at the very processes by which cancers evolve resistance. From yeast to vertebrates, heat shock protein 90 (HSP90) plays a unique role among molecular chaperones by promoting the evolution of heritable new traits. It does so by regulating the folding of a diverse portfolio of metastable client proteins, many of which mediate adaptive responses that allow organisms to adapt and thrive in the face of diverse challenges, including those posed by drugs. Guided by our previous work in pathogenic fungi, in which very modest HSP90 inhibition impairs resistance to mechanistically diverse antifungals, we examined the effect of similarly modest HSP90 inhibition on the emergence of resistance to antiestrogens in breast cancer models. Even though this degree of inhibition fell below the threshold for proteotoxic activation of the heat-shock response and had no overt anticancer activity on its own, it dramatically impaired the emergence of resistance to hormone antagonists both in cell culture and in mice. Our findings strongly support the clinical testing of combined hormone antagonist-low-level HSP90 inhibitor regimens in the treatment of metastatic estrogen receptor-positive breast cancer. At a broader level, they also provide promising proof of principle for a generalizable strategy to combat the pervasive problem of rapidly emerging resistance to molecularly targeted therapeutics.
101 citations
TL;DR: The results indicated that developmental competence is associated with oleic and stearic acid concentrations, which may contribute to the poor pregnancy outcomes in patients with PCOS.
Abstract: Context: Both polycystic ovary syndrome (PCOS) and obesity are associated with specific reproductive health complications, including lower oocyte quality and clinical pregnancy rates in assisted conception cycles, which may be a result of metabolism-induced changes in the oocyte through the microenvironment of follicular fluid. Free fatty acids (FFAs) are important biomedical indicators of abnormal lipid metabolism and have pronounced effects on cells, leading to changes in metabolism, cell growth, and differentiation Objective: Our objective was to determine the effect of FFA metabolism in plasma and follicular fluid on oocyte quality in the women with PCOS undergoing in vitro fertilization. Design and Setting: Ninety-three women undergoing in vitro fertilization treatment, including 55 with PCOS and 38 age-matched controls, were recruited. PCOS patients were divided into obese and nonobese subgroups on the basis of their body mass index. Main Outcome Measures: Embryo quality was morphologically assessed...
85 citations
TL;DR: Age and comorbidity were among factors that were associated with treatment completion, and rates of significant cardiac events were higher in those who did not complete therapy.
Abstract: Purpose Few data are available regarding adjuvant trastuzumab use in older women with early-stage breast cancer. We examined rates and predictors of adjuvant trastuzumab completion and cardiac events in this population. Patients and Methods We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients age ≥ 66 years with stage I to III breast cancer diagnosed between 2005 and 2009 who received trastuzumab. Completion of trastuzumab was defined as receipt of more than 270 days of therapy. We used multivariable logistic regression to examine patient, clinical, and geographic characteristics associated with trastuzumab completion. We also examined rates of hospital admissions for cardiac events. Results Among 2,028 women, most (71.2%) were younger than age 76 years and had a comorbidity score of 0 (66.8%); 85.2% received trastuzumab with chemotherapy. Overall, 1,656 women (81.7%) completed trastuzumab. Older patients and those with more comorbidity had lower odds of treatment ...
TL;DR: Air pollution in rural China has often been ignored, especially for the less developed west China, and with heavy dependence on biofuel combustion for heating, seasonality in rural areas is more profound than that in urban areas.
TL;DR: Although EEG suppression was associated with increasing anaesthetic administration and comorbidities, the hypothesis that intraoperative EEG suppression is a predictor of postoperative mortality was only supported if it was coincident with low MAP.
Abstract: Background Low bispectral index values frequently reflect EEG suppression and have been associated with postoperative mortality. This study investigated whether intraoperative EEG suppression was an independent predictor of 90 day postoperative mortality and explored risk factors for EEG suppression. Methods This observational study included 2662 adults enrolled in the B-Unaware or BAG-RECALL trials. A cohort was defined with >5 cumulative minutes of EEG suppression, and 1:2 propensity-matched to a non-suppressed cohort (≤5 min suppression). We evaluated the association between EEG suppression and mortality using multivariable logistic regression, and examined risk factors for EEG suppression using zero-inflated mixed effects analysis. Results Ninety day postoperative mortality was 3.9% overall, 6.3% in the suppressed cohort, and 3.0% in the non-suppressed cohort {odds ratio (OR) [95% confidence interval (CI)]=2.19 (1.48–3.26)}. After matching and multivariable adjustment, EEG suppression was not associated with mortality [OR (95% CI)=0.83 (0.55–1.25)]; however, the interaction between EEG suppression and mean arterial pressure (MAP) Conclusions Although EEG suppression was associated with increasing anaesthetic administration and comorbidities, the hypothesis that intraoperative EEG suppression is a predictor of postoperative mortality was only supported if it was coincident with low MAP. Clinical trial registration NCT00281489 and NCT00682825.
TL;DR: It appears that besides 1-PYR, metabolites of PHE could also be used as biomarkers to indicate the short-term dietary exposure to PAHs and urinary 3-BaA may serve as the biomarker for inhalation intake of high molecular weightPAHs.
TL;DR: Kir7.1 regulates the transition from quiescence to contractions in the pregnant uterus and may be a target for therapies to control uterine contractility.
Abstract: Abnormal uterine activity in pregnancy causes a range of important clinical disorders, including preterm birth, dysfunctional labour and post-partum haemorrhage. Uterine contractile patterns are controlled by the generation of complex electrical signals at the myometrial smooth muscle plasma membrane. To identify novel targets to treat conditions associated with uterine dysfunction, we undertook a genome-wide screen of potassium channels that are enriched in myometrial smooth muscle. Computational modelling identified Kir7.1 as potentially important in regulating uterine excitability during pregnancy. We demonstrate Kir7.1 current hyper-polarizes uterine myocytes and promotes quiescence during gestation. Labour is associated with a decline, but not loss, of Kir7.1 expression. Knockdown of Kir7.1 by lentiviral expression of miRNA was sufficient to increase uterine contractile force and duration significantly. Conversely, overexpression of Kir7.1 inhibited uterine contractility. Finally, we demonstrate that the Kir7.1 inhibitor VU590 as well as novel derivative compounds induces profound, long-lasting contractions in mouse and human myometrium; the activity of these inhibitors exceeds that of other uterotonic drugs. We conclude Kir7.1 regulates the transition from quiescence to contractions in the pregnant uterus and may be a target for therapies to control uterine contractility.
TL;DR: It is discovered that abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs.
Abstract: Aberrant DNA methylation is a hallmark of many cancers. Classically there are two types of endometrial cancer, endometrioid adenocarcinoma (EAC), or Type I, and uterine papillary serous carcinoma (UPSC), or Type II. However, the whole genome DNA methylation changes in these two classical types of endometrial cancer is still unknown. Here we described complete genome-wide DNA methylome maps of EAC, UPSC, and normal endometrium by applying a combined strategy of methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme digestion sequencing (MRE-seq). We discovered distinct genome-wide DNA methylation patterns in EAC and UPSC: 27,009 and 15,676 recurrent differentially methylated regions (DMRs) were identified respectively, compared with normal endometrium. Over 80% of DMRs were in intergenic and intronic regions. The majority of these DMRs were not interrogated on the commonly used Infinium 450K array platform. Large-scale demethylation of chromosome X was detected in UPSC, accompanied by decreased XIST expression. Importantly, we discovered that the majority of the DMRs harbored promoter or enhancer functions and are specifically associated with genes related to uterine development and disease. Among these, abnormal methylation of transposable elements (TEs) may provide a novel mechanism to deregulate normal endometrium-specific enhancers derived from specific TEs. DNA methylation changes are an important signature of endometrial cancer and regulate gene expression by affecting not only proximal promoters but also distal enhancers.
University of North Carolina at Chapel Hill1, Vanderbilt University2, Georgetown University3, Indiana University4, University of Alabama at Birmingham5, University of Pittsburgh6, University of Chicago7, University of Texas MD Anderson Cancer Center8, Harvard University9, Duke University10, University of Michigan11, Johns Hopkins University12, University of California, San Francisco13, University of North Carolina at Charlotte14
TL;DR: A modest benefit of irinotecan plus iniparib in progressive TNBC-BM is suggested, and this trial design is feasible and lays the foundation for additional studies for this treatment-refractory disease.
Abstract: Nearly half of patients with advanced triple negative breast cancer (TNBC) develop brain metastases (BM) and most will also have uncontrolled extracranial disease. This study evaluated the safety and efficacy of iniparib, a small molecule anti-cancer agent that alters reactive oxygen species tumor metabolism and penetrates the blood brain barrier, with the topoisomerase I inhibitor irinotecan in patients with TNBC-BM. Eligible patients had TNBC with new or progressive BM and received irinotecan and iniparib every 3 weeks. Time to progression (TTP) was the primary end point; secondary endpoints were response rate (RR), clinical benefit rate (CBR), overall survival (OS), toxicity, and health-related quality of life. Correlative endpoints included molecular subtyping and gene expression studies on pre-treatment archival tissues, and determination of germline BRCA1/2 status. Thirty-seven patients began treatment; 34 were evaluable for efficacy. Five of 24 patients were known to carry a BRCA germline mutation (4 BRCA1, 1 BRCA2). Median TTP was 2.14 months and median OS was 7.8 months. Intracranial RR was 12 %, while intracranial CBR was 27 %. Treatment was well-tolerated; the most common grade 3/4 adverse events were neutropenia and fatigue. Grade 3/4 diarrhea was rare (3 %). Intrinsic subtyping revealed 19 of 21 tumors (79 %) were basal-like, and intracranial response was associated with high expression of proliferation-related genes. This study suggests a modest benefit of irinotecan plus iniparib in progressive TNBC-BM. More importantly, this trial design is feasible and lays the foundation for additional studies for this treatment-refractory disease.
TL;DR: Wang et al. as mentioned in this paper show that homeowners' civic engagement, a necessary condition for the development of homeowners associations, is inadequate across urban communities. But, the lack of awareness of partitioned property ownership, the hidden costs of civic engagement and deficiency in social capital are the main obstacles that impede homeowners' participation in neighborhood development.
Abstract: China's massive transformation in urban governance, which is characterized by breaking the link between workplace and residence and consolidating state territorial agencies at the grassroots level, has profound implications for urban residents While community building is employed as a deliberate (top-down) approach to restore a governable urban society, the establishment, development and problems of bottom-up civic territorial organizations - homeowners associations - are garnering increased attention from academia Based on field research conducted in Guangzhou, Shenzhen and Meizhou in Guangdong Province from 2009 to 2011, we show that civic engagement, a necessary condition for the development of homeowners associations, is inadequate across urban communities To understand why, we identified and analyzed three elements - lack of awareness of partitioned property ownership, the hidden costs of civic engagement and deficiency in social capital - as factors that impede civic engagement across urban communities These elements also provide yardsticks for scholars to evaluate why, whether and how homeowners (dis-)engage from neighborhood affairs
TL;DR: The challenge will be to understand how to optimize the activity of targeted agents in the CNS and how to best incorporate them into the current treatment paradigms in order to improve outcomes for this patient population.
Abstract: Brain metastases are a major clinical problem in patients with advanced breast cancer, lung cancer, melanoma, and renal cell carcinoma. Initial treatment for patients with brain metastases typically includes radiotherapy, either whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or both. Surgical resection is generally reserved for good prognosis patients with limited/controlled extracranial metastases and a single brain lesion. Once patients progress through upfront treatment, the treatment approach is quite variable and there is no clearly defined standard-of-care. Over the past decade, the role of systemic therapies and in particular, targeted therapies has been increasingly explored in patients with brain metastases from solid tumors. For example, lapatinib has been studied as monotherapy, and in combination with capecitabine, in patients with HER2-positive breast cancer, and activity has been observed in both the upfront and refractory settings. In patients with nonsmall cell lung cancer (NSCLC), central nervous system (CNS) activity has been reported with gefinitib and erlotinib. Finally, in melanoma, the B-raf inhibitors vemurafenib and dabrafenib, and the immunomodulator, ipilumimab, have reported CNS activity. Moving forward, the challenge will be to understand how to optimize the activity of targeted agents in the CNS and how to best incorporate them into the current treatment paradigms in order to improve outcomes for this patient population.
Journal Article•
TL;DR: This overview of recent developments in the management of breast cancer brain metastases and current prospective trials of systemic therapies specifically for patients with BCBMs are reviewed, with a focus on novel pathway-specific therapies.
Abstract: Breast cancer brain metastases (BCBMs) are common in patients with advanced disease. Breast cancer subtype and performance status are the major determinants of the course of the disease and survival time following a diagnosis of brain metastasis. Unique challenges specific to the management of BCBMs include overcoming the blood-brain barrier and resistance to conventional systemic therapies, as BCBMs typically occur in the pretreated patient population. The development of new systemic therapies for breast cancer, coupled with improvements in trial design, imaging modalities, and methods of defining and measuring clinical endpoints, has led to a renewed interest in developing novel therapeutic approaches for BCBMs. In this overview, we will review recent developments in the management of BCBMs and current prospective trials of systemic therapies specifically for patients with BCBMs, with a focus on novel pathway-specific therapies.
TL;DR: Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit and the role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.
Abstract: Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P<.0001). Patients with HER2-amplified disease received the most lines (median, 4; P=.032) and the longest duration of chemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.
TL;DR: Among a population-based cohort of older women receiving trastuzumab, nearly one-third received non-standard chemotherapy, with the highest rates among the oldest women, and comorbidity was not associated with receipt of non- standard chemotherapy.
Abstract: Limited data are available regarding patterns of chemotherapy receipt and treatment-related toxicities for older women receiving adjuvant trastuzumab-based therapy. We used surveillance, epidemiology and end results (SEER)-Medicare data to identify patients ≥66 years with stage I–III breast cancer treated during 2005–2009, who received trastuzumab-based therapy. We examined patterns of chemotherapy receipt, and using multivariable logistic regression, we examined associations of age and comorbidity with non-standard chemotherapy. In propensity-weighted cohorts of women receiving standard and non-standard trastuzumab-based therapy, we also examined rates of (1) hospital events during the first 6 months of chemotherapy and (2) short-term survival. Among 2,106 women, 29.7 % were aged ≥76 and 66 % had a comorbidity score = 0. Overall, 31.3 % of women received non-standard chemotherapy. Compared to patients aged 66–70, older patients more often received non-standard chemotherapy [adjusted odds ratio (OR) = 4.1, 95 % confidence interval (CI) = 3.40–4.92 (ages 76–80); OR = 15.3, 95 %CI = 9.92–23.67 (age ≥ 80)]. However, comorbidity was not associated with receipt of non-standard chemotherapy. After propensity score adjustment, hospitalizations were more frequent in the standard (vs. non-standard) group (adjusted OR = 1.7, 95 % CI = 1.29–2.24). With a median follow-up of 2.8 years, 276 deaths occurred; the adjusted hazard ratio (HR) for death was lower in standard versus non-standard treated women (HR = 0.69, 95 % CI = 0.52–0.91). Among a population-based cohort of older women receiving trastuzumab, nearly one-third received non-standard chemotherapy, with the highest rates among the oldest women. Non-standard chemotherapy was associated with fewer toxicity-related hospitalizations but worse survival. Further exploration of treatment toxicities and outcomes for older women with HER2-positive breast cancer is warranted.
TL;DR: The role of tripchlorolide (T4), an extract of the natural herb Tripterygium wilfordii Hook F, in improving cognitive deficits and promoting the long-term potentiation of hippocampal slices via the N-methyl-D-aspartate receptor (NMDAR)-dependent signaling pathway is reported.
TL;DR: The highest concentrations of PAHs can be found in the surface layer of skin and decrease exponentially with depth, and migration of PAhs from surface to interior portions of meat is faster in lean than in fat or skin, and oPAHs and pPAHS can penetrate deeper than pPAhs.
Abstract: Smoked meat is widely consumed in many areas, particularly in rural southwest China. High concentrations of polycyclic aromatic hydrocarbons (PAHs) in smoked meat could lead to adverse dietary exposure and health risks. In this study, 27 parent PAHs (pPAHs), 12 nitrated PAHs (nPAHs), and 4 oxygenated PAHs (oPAHs) were measured in coal- and wood-smoked meats. The median concentrations of pPAHs, nPAHs, and oPAHs were as high as 1.66×10 3 , 4.29, and 20.5 ng/g in the coal-smoked meat and 2.54×10 3 , 7.32, and 9.26 ng/g in the wood-smoked meat, respectively. Based on the relative potency factors of individual PAHs, the calculated toxic equivalent (TEQ) values of all pPAHs were 22.1 and 75.1 ng TEQ/g for the wood- and coal-smoked meats, respectively. The highest concentrations of PAHs can be found in the surface layer of skin and decrease exponen- tially with depth. Surface PAH concentrations correlated with concentrations of PAHs in household air and with the concentration in emission exhaust. Migration of PAHs from surface to interior portions of meat is faster in lean than in fat or skin, and oPAHs and pPAHs can penetrate deeper than pPAHs. The penetration ability of PAHs is negatively corre- lated with the molecular weight.
TL;DR: SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.
Abstract: Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastases, but concerns over potential toxicity limit applications for larger lesions or those in eloquent areas. Fractionated stereotactic radiation therapy (SRT) is often substituted for SRS in these cases. We retrospectively analyzed the efficacy and toxicity outcomes of patients who received SRT at our institution. Seventy patients with brain metastases treated with SRT from 2006–2012 were analyzed. The rates of local and distant intracranial progression, overall survival, acute toxicity, and radionecrosis were determined. The SRT regimen was 25 Gy in 5 fractions among 87 % of patients. The most common tumor histologies were non-small cell lung cancer (37 %), breast cancer (20 %) and melanoma (20 %), and the median tumor diameter was 1.7 cm (range 0.4–6.4 cm). Median survival after SRT was 10.7 months. Median time to local progression was 17 months, with a local control rate of 68 % at 6 months and 56 % at 1 year. Acute toxicity was seen in 11 patients (16 %), mostly grade 1 or 2 with the most common symptom being mild headache. Symptomatic radiation-induced treatment change was seen on follow-up MRIs in three patients (4.3 %). SRT appears to be a safe and reasonably effective technique to treat brain metastases deemed less suitable for SRS, though dose intensification strategies may further improve local control.
TL;DR: This study demonstrates that in many countries, the mercury content of coal and petroleum locally consumed differ significantly from those locally produced, which would result in the resulting global mercury emissions from coal and Petroleum would be overestimated by 4.7 and 72%, respectively.
Abstract: The spatially resolved emission inventory is essential for understanding the fate of mercury. Previous global mercury emission inventories for fuel combustion sources overlooked the influence of fuel trading on local emission estimates of many countries, mostly developing countries, for which national emission data are not available. This study demonstrates that in many countries, the mercury content of coal and petroleum locally consumed differ significantly from those locally produced. If the mercury content in locally produced fuels were used to estimate emission, then the resulting global mercury emissions from coal and petroleum would be overestimated by 4.7 and 72%, respectively. Even higher misestimations would exist in individual countries, leading to strong spatial bias. On the basis of the available data on fuel trading and an updated global fuel consumption database, a new mercury emission inventory for 64 combustion sources has been developed. The emissions were mapped at 0.1° × 0.1° resolutio...
TL;DR: The data suggest that, among the groups of neurons involved in reproductive control, the kisspeptin neurons in the RP3V are likely among the earliest to undergo aging processes and thus participate in initiating the early reproductive decline.
TL;DR: Toxicity tests using human adenocarcinomic alveolar epithelial cell line A549 and small mouse monocyte-macrophage cell line J774A.1 were conducted to test toxicity of six PM samples from Beijing, indicating the presence of PM-induced inflammatory response and oxidative stress.
TL;DR: Insight into targets for improvement is provided including better coordination with plastic surgery and streamlining pre-operative testing and improve the timeliness of cancer care, as well as variation in timelier care based on procedure, provider, and patients’ sociodemographic characteristics.
Abstract: Few studies have examined care processes within providers’ and institutions’ control that expedite or delay care. The authors investigated the timeliness of breast cancer care at a comprehensive cancer center, focusing on factors influencing the time from initial consultation to first definitive surgery (FDS). The care of 1,461 women with breast cancer who underwent surgery at Dana-Farber/Brigham and Women’s Cancer Center from 2011 to 2013 was studied. The interval between consultation and FDS was calculated to identify variation in timeliness of care based on procedure, provider, and patients’ sociodemographic characteristics. Targets of 14 days for lumpectomy and mastectomy and 28 days from mastectomy with immediate reconstruction were set and used to define delay. Mean days between consultation and FDS was 21.6 (range 1–175, sd 15.8) for lumpectomy, 36.7 (5–230, 29.1) for mastectomy, and 37.5 (7–111, 16) for mastectomy with reconstruction. Patients under 40 were less likely to be delayed (OR = 0.56, 95 % CI = 0.33–0.94, p = 0.03). Patients undergoing mastectomy alone (OR = 2.64, 95 % CI = 1.80–3.89, p < 0.0001) and mastectomy with immediate reconstruction (OR = 1.34 95 % CI = 1.00–1.79, p = 0.05) were more likely to be delayed when compared to lumpectomy. Substantial variation in surgical timeliness was identified. This study provides insight into targets for improvement including better coordination with plastic surgery and streamlining pre-operative testing. Cancer centers may consider investing in efforts to measure and improve the timeliness of cancer care.
TL;DR: Patients with recently diagnosed MBC have high informational needs and decreased overall QOL and additional research and supportive services meeting the informational and psychosocial needs of patients living with MBC are warranted.
Abstract: BACKGROUND Little is known about the informational needs and quality of life (QOL) of patients with metastatic breast cancer (MBC) within the first year of their diagnosis. OBJECTIVES To describe the informational needs and QOL of patients with MBC within the first year of diagnosis, and to identify sociodemographic and medical factors that may be associated with informational needs and QOL. METHODS 52 patients (50 women, 2 men) enrolled within a year of diagnosis of MBC completed a cross-sectional, self-administered paper survey that included patient demographics, the Toronto Informational Needs Questionnaire-Breast Cancer (TINQ), the Hospital Anxiety and Depression Scale (HADS), and Medical Outcomes Study Short Form-36 (SF-36). High informational need was defined as a TINQ score of ≥ 200. RESULTS Of the total 52 patients, 69% (35/52) had high informational needs, 20% met the criteria for anxiety (HADS-Anxiety score, ≥ 11), and 8% met the criteria for depression. SF-36 scores were lower in all 8 subscales compared with the general population. Multivariate analyses showed that patients who were married or living as married (OR, 6.1; 95% CI, 1.4-28.9) and patients with de novo MBC (OR, 2.8; 95% CI, 0.5-14.3) or a shorter disease-free interval (DFI; < 5 years; OR, 24.2; 95% CI, 3.1-187.4) were more likely to have more informational needs (C statistic, 0.824) than were patients with a longer DFI (≥ 5 years). LIMITATIONS This is a small cross-sectional study of a single academic institution. CONCLUSIONS Patients with recently diagnosed MBC have high informational needs and decreased overall QOL. Additional research and supportive services meeting the informational and psychosocial needs of patients living with MBC are warranted.