Impact of changing US cigarette smoking patterns on incident cancer: Risks of 20 smoking-related cancers among the women and men of the NIH-AARP cohort

Background: Historically, US women started smoking at a later age than men and had lower relative risks for smoking-related cancers. However, more recent birth cohorts of women and men have similar smoking histories and have now reached the high-risk age for cancer. The impact of these changes on cancer incidence has not been systematically examined. Methods: Relative risks (RR), 95% confidence intervals (CI) and attributable fractions were calculated for cigarette smoking and incidence of 20 smoking-related cancers in 186 057 women and 266 074 men of the National Institutes of Health-AARP cohort, aged 50 to 71 years in 1995 and followed for 11 years. Results: In the cohort, which included participants born between 1924 and 1945, most women and men started smoking as teenagers. RRs for current vs never smoking were similar in women and men for the following cancers: lung squamous-cell (RR women: 121.4, 95% CI: 57.3–257.4; RR men:114.6, 95% CI: 61.2–214.4), lung adenocarcinoma (RR women: 11.7, 95% CI: 9.8–14.0; RR men: 15.6, 95% CI: 12.5–19.6), laryngeal (RR women: 37.0, 95% CI: 14.9–92.3; RR men: 13.8, 95% CI: 9.3–20.2), oral cavity-pharyngeal (RR women:4.4, 95% CI: 3.3–6.0; RR men: 3.8, 95% CI: 3.0–4.7), oesophageal squamous cell (RR women: 7.3, 95% CI: 3.5–15.5; RR men: 6.2, 95% CI: 2.8–13.7), bladder (RR women: 4.7, 95% CI: 3.7–5.8; RR men: 4.0, 95% CI: 3.5–4.5), colon (RR women: 1.3, 95% CI: 1.2–1.5; RR men: 1.3, 95% CI: 1.1–1.4), and at other sites, with similar attributable fractions. Conclusions: RRs for current smoking and incidence of many smoking-related cancers are now similar in US women and men, likely reflecting converging smoking patterns

The current practice of intra-aortic balloon counterpulsation: results from the Benchmark Registry

OBJECTIVES This study presents clinical data from the first large registry of aortic counterpulsation, a computerized database that incorporates prospectively gathered data on indications for intra-aortic balloon counterpulsation (IABP) use, patient demographics, concomitant medication and in-hospital outcomes and complications. BACKGROUND The intra-aortic balloon pump (IABP) is widely used to provide circulatory support for patients experiencing hemodynamic instability due to myocardial infarction, cardiogenic shock, or in very high risk patients undergoing angioplasty or coronary artery bypass grafting. METHODS Between June 1996 and August 2000, 203 hospitals worldwide (90% U.S., 10% non-U.S.) collected 16,909 patient case records (68.8% men, 31.2% women; mean age 65.9 ± 11.7 years). RESULTS The most frequent indications for use of IABP were as follows: to provide hemodynamic support during or after cardiac catheterization (20.6%), cardiogenic shock (18.8%), weaning from cardiopulmonary bypass (16.1%), preoperative use in high risk patients (13.0%) and refractory unstable angina (12.3%). Major IABP complications (major limb ischemia, severe bleeding, balloon leak, death directly due to IABP insertion or failure) occurred in 2.6% of cases; in-hospital mortality was 21.2% (11.6% with the balloon in place). Female gender, high age and peripheral vascular disease were independent predictors of a serious complication. CONCLUSIONS This registry provides a useful tool for monitoring the evolving practice of IABP. In the modern-day practice of IABP, complication rates are generally low, although in-hospital mortality remains high. There is an increased risk of major complications in women, older patients and patients with peripheral vascular disease

Intra-aortic balloon counterpulsation in US and non-US centres: results of the Benchmark® Registry

Aims To examine differences in patient characteristics and outcomes in 19 636 patients enrolled in the USA and 3027 patients enrolled in other countries undergoing intra-aortic balloon pump (IABP) counterpulsation. Methods and results Indications for IABP use; a larger percentage of US patients were identified as ‘early support and stabilization for angiography or angioplasty' (21.1% US vs 11.8% non-US), and ‘pre-operative support for high-risk CABG' (15.9% vs 6.6%). A smaller percentage of US patients vs non-US patients were identified as ‘weaning from cardiopulmonary bypass' (14.3% vs 28.2%), and ‘refractory ventricular failure' (6.2% vs 9.8%). One out of five patients in both groups was listed as ‘cardiogenic shock' (18.9% US vs 20.2% non-US). All cause, risk-adjusted, in-hospital mortality (20.1% vs 28.7%; P<0.001), and mortality with IABP in place (10.8% vs 18.0%; P<0.001) were lower at US vs non-US sites. In both US and non-US institutions, IABP associated complication rates, such as IABP-related mortality (0.05% vs 0.07%), major limb ischaemia (0.9% vs 0.8%), and severe bleeding (0.9% vs 0.8%), were low. Conclusions IABP counterpulsation is deployed at an earlier clinical stage in US patients. Mortality rates are higher for non-US patients, particularly for patients with non-surgery cardiac interventions, even after adjusting for risk factors. Complication rates were low. Physicians should therefore not be reluctant to use IABP in high-risk patients undergoing cardiac procedure

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer

Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case-control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine-phosphate-guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59-0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63-0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation

Outdoor Ultrafine Particulate Matter and Risk of Lung Cancer in Southern California

Rationale: Particulate matter ⩽2.5 μm in aerodynamic diameter (PM2.5) is an established cause of lung cancer, but the association with ultrafine particulate matter (UFP; aerodynamic diameter < 0.1 μm) is unclear. Objectives: To investigate the association between UFP and lung cancer overall and by histologic subtype. Methods: The Los Angeles Ultrafines Study includes 45,012 participants aged ⩾50 years in southern California at enrollment (1995-1996) followed through 2017 for incident lung cancer (n = 1,770). We estimated historical residential ambient UFP number concentrations via land use regression and back extrapolation using PM2.5. In Cox proportional hazards models adjusted for smoking and other confounders, we estimated associations between 10-year lagged UFP (per 10,000 particles/cm3 and quartiles) and lung cancer overall and by major histologic subtype (adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). We also evaluated relationships by smoking status, birth cohort, and historical duration at the residence. Measurements and Main Results: UFP was modestly associated with lung cancer risk overall (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.99-1.08]). For adenocarcinoma, we observed a positive trend among men; risk was increased in the highest exposure quartile versus the lowest (HR, 1.39 [95% CI, 1.05-1.85]; P for trend = 0.01) and was also increased in continuous models (HR per 10,000 particles/cm3, 1.09 [95% CI, 1.00-1.18]), but no increased risk was apparent among women (P for interaction = 0.03). Adenocarcinoma risk was elevated among men born between 1925 and 1930 (HR, 1.13 [95% CI, 1.02-1.26] per 10,000) but not for other birth cohorts, and was suggestive for men with ⩾10 years of residential duration (HR, 1.11 [95% CI, 0.98-1.26]). We found no consistent associations for women or other histologic subtypes. Conclusions: UFP exposure was modestly associated with lung cancer overall, with stronger associations observed for adenocarcinoma of the lung

Survivorship: sleep disorders, version 1.2014.

Sleep disorders, including insomnia and excessive sleepiness, affect a significant proportion of patients with cancer and survivors, often in combination with fatigue, anxiety, and depression. Improvements in sleep lead to improvements in fatigue, mood, and quality of life. This section of the NCCN Guidelines for Survivorship provides screening, diagnosis, and management recommendations for sleep disorders in survivors. Management includes combinations of sleep hygiene education, physical activity, psychosocial interventions, and pharmacologic treatments

Survivorship: cognitive function, version 1.2014.

Cognitive impairment is a common complaint among cancer survivors and may be a consequence of the tumors themselves or direct effects of cancer-related treatment (eg, chemotherapy, endocrine therapy, radiation). For some survivors, symptoms persist over the long term and, when more severe, can impact quality of life and function. This section of the NCCN Guidelines for Survivorship provides assessment, evaluation, and management recommendations for cognitive dysfunction in survivors. Nonpharmacologic interventions (eg, instruction in coping strategies; management of distress, pain, sleep disturbances, and fatigue; occupational therapy) are recommended, with pharmacologic interventions as a last line of therapy in survivors for whom other interventions have been insufficient

NCCN Guidelines Insights: Survivorship, Version 2.2019.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of cancer and cancer treatment to aid healthcare professionals who work with survivors of adult-onset cancer. Guidance is also provided to help promote physical activity, weight management, and proper immunizations in survivors and to facilitate care coordination to ensure that all needs are addressed. These NCCN Insights summarize some of the topics discussed by the NCCN Survivorship Panel during the 2019 update of the guidelines, including the survivorship population addressed, ways to improve care coordination, and pain management

NCCN Guidelines Insights: Survivorship, Version 2.2020.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies