High Stroke Rate in Patients With Medically Managed Asymptomatic Carotid Stenosis at an Academic Center in the Southeastern United States.

BACKGROUND: Although the publication of randomized clinical trials defining the benefit of carotid endarterectomy (CEA) for asymptomatic carotid stenosis, medical management of carotid stenosis has changed significantly. With antiplatelet agents and statins, some question whether these trials are still relevant, suggesting that asymptomatic patients with >70% internal carotid artery (ICA) stenosis may do better with medial management alone, lessening the need for CEA and carotid stenting. The Vascular Quality Initiative (VQI) registry has shown that there are wide practice variations regarding the degree of stenosis that prompts surgical intervention but there are few reports of outcomes in patients who do not undergo intervention. We sought to determine the clinical outcomes of the >70% carotid stenosis patients who are treated with medical management alone at our institution. METHODS: We identified all patients with ICA stenosis >70% based on hemodynamic consensus criteria (peak systolic velocity >230 cm/s) in our peripheral vascular laboratory from January 2013 through December 2016. With a retrospective chart review, demographics, comorbid conditions, medications, radiographic studies, clinical follow-up, interventions, and outcomes at 2 years were included. Descriptive statistics were used to define these variables. RESULTS: One hundred and seventy three patients were identified with medically managed asymptomatic >70% ICA stenosis based on hemodynamic criteria on duplex ultrasound. The mean age was 67.5 years, 49% were male, 64% were White, 14% were Black, 13% race was undisclosed, 89% were prescribed antiplatelet therapy, 85% were prescribed a statin, and 60% had hypertension controlled to <140/90. Twenty patients (11.5%) experienced a cerebrovascular event during the 2-year study period. There were eight patients with transient ischemic attack, 10 with ipsilateral strokes, and 2 with strokes in unrelated territories. CONCLUSIONS: Despite good adherence to current recommendations for medical therapy, patients at our institution are developing symptomatic carotid disease at a rate similar to that reported in historical clinical trials. These data supports the concept that advances in medical management have not resulted in reduced stroke rates in asymptomatic patients with high-grade carotid stenosis at a large academic institution located in the southeastern United States. CEA and stenting provide a significant risk reduction and should be considered more often in this patient population.

[Characteristics of nutrient accumulation and vertical spatial distribution in Cunninghamia lanceolata plantation with different stand densities]. / ä¸åŒæž—åˆ†å¯†åº¦æ‰æœ¨æž—å »åˆ†ç§¯ç´¯ä¸Žåž‚ç›´ç©ºé—´åˆ†é .

The growth, biomass, nutrient content and accumulation as well as the vertical distribution of nutrient accumulation in Cunninghamia lanceolata plantation across densities of 1800, 3000, 4500 trees·hm-2 were stu-died in order to provide scientific basis for efficient cultivation of C. lanceolata plantation. The total amounts of nutrients accumulated in C. lanceolata plantation with 1800, 3000, 4500 trees·hm-2 were 1311.57, 2531.55 and 2307.33 kg·hm-2, respectively. There were significant variations among different densities. Under the same density, the order of nutrient content and accumulation in C. lanceolata plantation was total N > total K > total Ca > total Mg > total P. Moreover, the amount of nutrients in trunk and bark decreased with the increases of tree height. The amount of nutrient accumulation in persistent withered branch and leaf were allocated from middle to the upper part of tree, while the opposite was observed for fresh branch and leaf. N accumulation increased with the increases of stand densities, while the other nutrients first increased then decreased. The order of the amount of nutrient accumulation in trunk, bark, root, persistent withered branch, persistent withered leaf and litter among different densities was 4500 > 3000 > 1800 trees·hm-2, and was 3000 > 1800 > 4500 trees·hm-2 in fresh branch and leaf, and 1800 > 3000 > 4500 trees·hm-2 in understory. Under the densities of 1800 and 4500 trees·hm-2, the nutrient distribution ratio in bark was the largest, accounting for 21.6% and 19.4%. In 3000 trees·hm-2, the distribution ratio of fresh leaves reached its maximum, accounting for about 22.9%, and the next was fresh branches, which had a distribution ratio of about 17.8%. 3000 trees·hm-2 was the most appropriate density for nutrient accumulation and distribution in C. lanceolata plantation.

Social support and outcomes in older adults with lung cancer.

BACKGROUND: Insufficient social support is associated with increased mortality among older adults. Lung cancer is primarily a disease of older adults and is the leading cause of all cancer deaths. We assessed the association of social support with outcomes among older adults with lung cancer. MATERIALS AND METHODS: Adults age 65 and older with lung cancer with a completed geriatric assessment (GA) were assessed. Emotional social support (ES) and tangible (material, instrumental) support (TS) measures and patient characteristics were obtained from the GA. The electronic health record was used to extract clinical variables. Simple linear regression models evaluated the association between social support scales with patient and clinical factors. RESULTS: 79 adults were assessed. White race was positively associated with ES score (p=.04), while higher BMI (p=.03), depression (p=.03) and anxiety (p=.02) were associated with worse ES. Higher BMI was associated with higher/better TS score (p=.02) while living alone was associated with lower/worse TS score (p=.03). Completion of platinum-based doublet chemotherapy with immunotherapy as planned was associated with higher ES scores (p=.02) and higher TS scores (p=.02). Disease progression was associated with lower ES scores (p=.03). CONCLUSION: Social support may influence clinical outcomes in older adults with lung cancer. As lung cancer often portends to poor prognosis, social support may be an important prognostic indicator.

Posttraumatic Stress Disorder Symptom Trajectories in ICU Family Caregivers.

To use latent class growth analysis to identify posttraumatic stress disorder symptom trajectories in ICU family caregivers. DESIGN: Prospective cohort study. SETTING: The medical ICU at a tertiary-care center in the United States. PARTICIPANTS: Adult patients experiencing acute cardiorespiratory failure (defined as requiring at least one of the following: 1) vasopressors, 2) noninvasive positive pressure ventilation, 3) high-flow nasal cannula, or 4) mechanical ventilation) were enrolled in a pair with their primary family caregivers. MEASUREMENTS AND MAIN RESULTS: Participants were enrolled within the first 48 hours of ICU admission. Family caregiver posttraumatic stress disorder symptoms were measured using the Impact of Events Scale-Revised at four time points: at enrollment, shortly after ICU discharge, and at 3 and 6 months after ICU discharge. The data were examined using latent class growth analysis to identify posttraumatic stress disorder symptom trajectories. Two distinct symptom trajectories were identified: a persistently high trajectory, characterized by high posttraumatic stress disorder symptoms at initial assessment, which remained elevated over time, and a persistently low trajectory, characterized by low posttraumatic stress disorder symptoms at initial assessment, which remained low over time. Approximately two-thirds of caregivers belonged to the persistently high trajectory, and one-third of caregivers belonged to the persistently low trajectory. CONCLUSIONS: Using latent class growth analysis to measure 6-month ICU family caregiver posttraumatic stress disorder symptom trajectories, we identified two distinct trajectories (persistently low and persistently high). A larger cohort study is warranted to further delineate posttraumatic stress disorder trajectories in this population, with the ultimate goal of targeting high-risk caregivers for interventions to reduce psychologic distress and improve long-term caregiver outcomes.

Serial Assessment of Depression and Anxiety by Patients and Providers in Women Receiving Chemotherapy for Early Breast Cancer.

BACKGROUND: Depression and anxiety are common in patients with breast cancer and associated with worse quality of life and treatment outcomes. Yet, these symptoms are often underrecognized and undermanaged in oncology practice. The objective of this study was to describe depression and anxiety severity and associated patient factors during adjuvant or neoadjuvant chemotherapy in women with early breast cancer using repeated single-item reports. MATERIALS AND METHODS: Depression and anxiety were measured from consecutive patients and their clinicians during chemotherapy infusion visits. Associations between psychiatric symptoms and patient characteristics were assessed using Fisher's exact tests for categorical variables and t tests for continuous variables. The joint relationship of covariates significant in unadjusted analyses was evaluated using log-binomial regression. Cohen's kappa was used to assess agreement between patient- and clinician-reported symptoms. RESULTS: In a sample of 256 patients, 26% reported at least moderately severe depression, and 41% reported at least moderately severe anxiety during chemotherapy, representing a near doubling in the prevalence of these symptoms compared with before chemotherapy. Patient-provider agreement was fair (depression: κ = 0.31; anxiety: κ = 0.28). More severe psychiatric symptoms were associated with being unmarried, having worse function, endorsing social activity limitations, using psychotropic medications, and having a mental health provider. In multivariable analysis, social activity limitations were associated with more severe depression (relative risk [RR], 2.17; 95% confidence interval [CI], 1.36-3.45) and anxiety (RR, 1.48; 95% CI, 1.05-2.09). CONCLUSION: Oncologists frequently underestimate patients' depression and anxiety and should consider incorporating patient-reported outcomes to enhance monitoring of mental health symptoms. IMPLICATIONS FOR PRACTICE: In this sample of 256 patients with breast cancer, depression and anxiety, measured using single-item toxicity reports completed by patients and providers, were very common during adjuvant or neoadjuvant chemotherapy. Patient-reported depression and anxiety of at least moderate severity were associated with multiple objective indicators of psychiatric need. Unfortunately, providers underrecognized the severity of their patients' mental health symptoms. The use of patient-reported, single-item toxicity reports can be incorporated into routine oncology practice and provide clinically meaningful information regarding patients' psychological health.

Patient-reported symptom severity, interference with daily activities, and adverse events in older and younger women receiving chemotherapy for early breast cancer.

BACKGROUND: To the authors' knowledge, it is unknown whether patient-reported symptom severity and symptom interference with daily activities differ between younger (aged <65 years) and older (aged ≥65 years) women receiving similar chemotherapy regimens for early breast cancer (EBC). METHODS: Study participants rated 17 side effects of chemotherapy regimens currently in use in clinical practice (2014-2019). RESULTS: Of 284 women with EBC (stage I-III), approximately 57% were aged <65 years and 43% were aged ≥65 years. For anthracycline-based regimens, a higher percentage of younger women reported moderate, severe, or very severe (MSVS) hot flashes (49% vs 18%) (P < .001). For nonanthracycline regimens, a higher percentage of younger women reported MSVS hot flashes (38% vs 19%) (P = .009) and a lower percentage reported MSVS arthralgia (28% vs 49%) (P = .005). With regard to symptom interference with daily activities, a higher percentage of younger women being treated with anthracycline-based regimens reported MSVS hot flashes (32% vs 7%) (P = .001) and myalgia (38% vs 18%) (P = .02). For nonanthracycline chemotherapy, a higher percentage of younger women reported MSVS interference for hot flashes (26% vs 9%) (P = .006) and lower percentages reported abdominal pain (13% vs 28%) (P = .02). Overall, there were no significant differences noted among younger versus older patients with regard to hospitalizations (19% vs 12%; P = .19), dose reductions (34% vs 31%; P = .50), dose delays (22% vs 25%; P = .59), or early treatment discontinuation (16% vs 16%; P = .9546). CONCLUSIONS: Older and younger women with EBC who were treated with identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events. LAY SUMMARY: In this study, women receiving chemotherapy for early breast cancer rated the severity of 17 symptoms and symptom interference with their activities of daily living. Older (aged ≥65 years) and younger (aged <65 years) women who received identical chemotherapy regimens generally experienced similar levels of symptom severity, symptom-related interference with daily activities, and adverse events.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer.

BACKGROUND: The National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, collected alongside the clinician-reported Common Terminology Criteria for Adverse Events, enables comparisons of patient and clinician reports on treatment toxicity. METHODS: In a multisite study of women receiving chemotherapy for early-stage breast cancer, symptom reports were collected on the same day from patients and their clinicians for 17 symptoms; their data were not shared with each other. The proportions of moderate, severe, or very severe patient-reported symptom severity were compared with the proportions of clinician-rated grade 2, 3, or 4 toxicity. Patient-clinician agreement was assessed via κ statistics. Chi-square tests investigated whether patient characteristics were associated with patient-clinician agreement. RESULTS: Among 267 women, the median age was 58 years (range, 24-83 years), and 26% were nonwhite. There was moderate scoring agreement (κ = 0.413-0.570) for 53% of symptoms, fair agreement for 41% (κ = 0.220-0.378), and slight agreement for 6% (κ = 0.188). For example, patient-reported and clinician-rated percentages were 22% and 8% for severe or very severe fatigue, 41% and 46% for moderate fatigue, 32% and 39% for mild fatigue, and 6% and 7% for none. Clinician severity scores were lower for nonwhite patients in comparison with white patients for peripheral neuropathy, nausea, arthralgia, and dyspnea. CONCLUSIONS: Although clinician reporting of symptoms is common practice in oncology, there is suboptimal agreement with the gold standard of patient self-reporting. These data provide further evidence supporting the integration of patient-reported outcomes into oncological clinical research and clinical practice to improve monitoring of symptoms as well as timely interventions for symptoms.

Pretreatment Dietary Patterns Are Associated with the Presence of Nutrition Impact Symptoms 1 Year after Diagnosis in Patients with Head and Neck Cancer.

BACKGROUND: Dietary inflammatory potential could impact the presence and severity of chronic adverse treatment effects among patients with head and neck cancer. The objective of this study was to determine whether pretreatment dietary patterns are associated with nutrition impact symptoms (NIS) as self-reported 1 year after diagnosis. METHODS: This was a longitudinal study of 336 patients with newly diagnosed head and neck cancer enrolled in the University of Michigan Head and Neck Specialized Program of Research Excellence. Principal component analysis was utilized to derive pretreatment dietary patterns from food frequency questionnaire data. Burden of seven NIS was self-reported 1 year after diagnosis. Associations between pretreatment dietary patterns and individual symptoms and a composite NIS summary score were examined with multivariable logistic regression models. RESULTS: The two dietary patterns that emerged were prudent and Western. After adjusting for age, smoking status, body mass index, tumor site, cancer stage, calories, and human papillomavirus status, significant inverse associations were observed between the prudent pattern and difficulty chewing [OR 0.44; 95% confidence interval (CI), 0.21-0.93; P = 0.03], dysphagia of liquids (OR 0.38; 95% CI, 0.18-0.79; P = 0.009), dysphagia of solid foods (OR 0.46; 95% CI, 0.22-0.96; P = 0.03), mucositis (OR 0.48; 95% CI, 0.24-0.96; P = 0.03), and the NIS summary score (OR 0.45; 95% CI, 0.22-0.94; P = 0.03). No significant associations were observed between the Western pattern and NIS. CONCLUSIONS: Consumption of a prudent diet before treatment may help reduce the risk of chronic NIS burden among head and neck cancer survivors. IMPACT: Dietary interventions are needed to test whether consumption of a prudent dietary pattern before and during head and neck cancer treatment results in reduced NIS burden.

Feasibility Outcomes of a Pilot Randomized Clinical Trial to Increase Cruciferous and Green Leafy Vegetable Intake in Posttreatment Head and Neck Cancer Survivors.

BACKGROUND: Higher intakes of cruciferous vegetables (CVs) and green leafy vegetables (GLVs) in observational studies are associated with improvements in survival and cancer-related biomarkers in patients diagnosed with head and neck cancer (HNC). These results have yet to be corroborated in a randomized clinical trial (RCT). OBJECTIVE: Determine the feasibility of implementing a 12-week RCT to increase CV and GLV intake in posttreatment HNC survivors. DESIGN AND PARTICIPANTS: This was a two-arm RCT conducted among 24 posttreatment HNC survivors. Survivors were recruited from a southeastern, National Cancer Institute-designated Comprehensive Cancer Center between January 2015 and September 2016. INTERVENTION: There were two groups: (1) an experimental group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist stressing 2.5 cups per week CVs and 3.5 cups per week GLVs, and (2) an attention control group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist focusing on general healthy eating for cancer survivors. Participants completed a baseline survey, three 24-hour dietary recalls, phlebotomy, and anthropometric measures prior to randomization and at the end of the 12-week study period. The experimental group also completed weekly vegetable record recalls. MAIN OUTCOME MEASURES: Primary outcomes included feasibility, recruitment, retention, adherence, and safety. Secondary outcomes included inflammatory markers and carotenoids. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were generated for demographic, epidemiological, and clinical variables as well as the primary feasibility outcomes. Between- and within-group comparisons of mean serum cytokine and carotenoid levels were performed using appropriate statistical tests depending on their respective distributions for the purpose of generating preliminary effect sizes. RESULTS: Overall, 350 incident HNC cases were screened for eligibility, and 98 were eligible for study participation. Reasons for ineligibility and exclusion included deceased (n=93); wrong or inactive telephone numbers, or unable to be reached, or lost to follow-up (n=93); not meeting inclusion criteria (n=39); and too ill to participate (n=27). Of the 98 eligible HNC cases, 24 agreed to participate, for an enrollment rate of 25%. The most common reason for nonparticipation was distance (n=48), as participants were asked to report for two on-site assignments. The retention rate was 96%. Mean intervention adherence rates for weekly goals were 67% CV, 74% GLV, and 71% overall. Completion rate of weekly counseling calls was 90%. The experimental group reported an overall mean increase of 5.5 cups GLV and 3.5 cups CV per week from baseline intake, respectively. No significant between- or within-arm differences were observed for inflammatory markers or carotenoids. CONCLUSION: A posttreatment intervention aimed at increasing CV and GLV intake in HNC survivors is feasible. A larger RCT is needed to assess the efficacy of this intervention on disease outcomes.

Higher carbohydrate intake is associated with increased risk of all-cause and disease-specific mortality in head and neck cancer patients: results from a prospective cohort study.

No studies have evaluated associations between carbohydrate intake and head and neck squamous cell carcinoma (HNSCC) prognosis. We prospectively examined associations between pre- and post-treatment carbohydrate intake and recurrence, all-cause mortality, and HNSCC-specific mortality in a cohort of 414 newly diagnosed HNSCC patients. All participants completed pre- and post-treatment Food Frequency Questionnaires (FFQs) and epidemiologic surveys. Recurrence and mortality events were collected annually. Multivariable Cox Proportional Hazards models tested associations between carbohydrate intake (categorized into low, medium and high intake) and time to recurrence and mortality, adjusting for relevant covariates. During the study period, there were 70 deaths and 72 recurrences. In pretreatment analyses, high intakes of total carbohydrate (HR: 2.29; 95% CI: 1.23-4.25), total sugar (HR: 3.03; 95% CI: 1.12-3.68), glycemic load (HR: 2.10; 95% CI: 1.15-3.83) and simple carbohydrates (HR 2.26; 95% CI 1.19-4.32) were associated with significantly increased risk of all-cause mortality compared to low intake. High intakes of carbohydrate (HR 2.45; 95% CI: 1.23-4.25) and total sugar (HR 3.03; 95% CI 1.12-3.68) were associated with increased risk of HNSCC-specific mortality. In post-treatment analyses, medium fat intake was significantly associated with reduced risk of recurrence (HR 0.08; 95% CI 0.01-0.69) and all-cause mortality (HR 0.27; 95% CI 0.07-0.96). Stratification by tumor site and cancer stage in pretreatment analyses suggested effect modification by these factors. Our data suggest high pretreatment carbohydrate intake may be associated with adverse prognosis in HNSCC patients. Clinical intervention trials to further examine this hypothesis are warranted.

X-ray Reflectivity Studies on the Mixed Langmuir-Blodgett Monolayers of Thiol-Capped Gold Nanoparticles, Dipalmitoylphosphatidylcholine, and Sodium Dodecyl Sulfate.

Langmuir-Blodgett monolayers of thiolated gold nanoparticles mixed with dipalmitoylphosphatidylcholine/sodium dodecyl sulfate (DPPC/SDS) were investigated by combining the X-ray reflectivity, grazing-incident scattering, and TEM analyses to reveal the in-depth and in-plane organization and the 2D morphology of such mixed monolayers. It was found that the addition of a charged single-tail surfactant to the thiolated Au nanoparticle monolayer helps to stabilize the Au nanoparticle monolayer and to strengthen the mechanical property of the mixed monolayer film. For mixing with lipids, it was found that the thiolated gold nanoparticles could be pushed on top of the lipid monolayer when the mixed monolayer is compressed. At a typical comparable total surface area ratio of gold nanoparticle to lipid, the thiolated gold nanoparticles could form a uniform domain on top of the DPPC monolayer. When there are more thiolated gold nanoparticles than that could be supported by the lipid monolayer, domain overlapping could occur to form bilayer gold nanoparticle domains at some regions. At low total surface area ratio of thiolated gold nanoparticle to lipid, the thiolated gold nanoparticles tend to form a connected threadlike aggregation structure. Evidently, the morphology of the thiolated gold nanoparticle monolayer is highly depending on the total surface area ratio of the thiolated gold nanoparticle to lipid. SDS is found to have a dispersion power capable of dispersing the originally uniform Au-8C nanoparticle domain of the mixed Au-8C/DPPC monolayer into a foamlike structure for the mixed Au-8C/SDS/DPPC monolayer. It is evident that not only the concentration ratio but also the size and shape of the template formed by the amphiphilic molecules and their interaction with the thiolated gold nanoparticles can all have great effects on the organizational structure as well as morphology of the thiolated gold nanoparticle monolayer.

In vivo imaging in tumor-bearing animals and pharmacokinetics of PEGylated liposomes modified with RGD cyclopeptide / 药学学报

The hydroxycamptothecin (HCPT) PEGylated liposomes (HCPT-LP) were modified with RGD cyclopeptide formed the tumor-targeting liposomes (HCPT-RGD-LP). HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg x kg(-1) to rats. The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared. The HCPT distribution in heart, liver, spleen, lung, kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection. The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging. The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes (DiR-LP) and DiR-LP modified with RGD cyclopeptide (DiR-RGD-LP). The results showed that there was no significant difference (P > 0.05) of main pharmacokinetic parameters t1/2beta, CL, V(c), AUC(0-48 h), AUC(0-inifinity), MRT(0-48 h), MRT(0-infinity) between HCPT-RGD-LP and HCPT-LP. HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver. The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging. It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.