Baseline Characteristics of Participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

-Diuretics and ss-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and alpha-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged >/=55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged >/=70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics?     

Insulin resistance and endothelial function in children and adolescents

Aims

Insulin resistance (IR) impairs cellular response to insulin due to a dysfunction in glucose metabolism, associated with an increased cardiovascular risk. The aim of our study was to investigate the relationship among homeostasis model assessment index (HOMA index), endothelial function and vascular morphology in order to better stratify cardiovascular risk in children and adolescents.

Methods

A total of 150 children and adolescents (55 pre-pubertal, mean age 10.4 ± 3.1 years) were enrolled. Anthropometric [body mass index (BMI), waist circumference (WC)], laboratory [blood lipids, inflammatory markers, insulinemia, glycemia], HOMA index and ultrasound parameters [flow-mediated dilatation (FMD), common carotid intima–media thickness (cIMT) and antero-posterior diameter of infra-renal abdominal aorta (APAO)] were assessed.

Results

cIMT was positively related to age (r = 0.274, p < 0.01), BMI (r = 0.318, p < 0.01), WC (r = 0.315, p < 0.01) and triglycerides (r = 0.230, p < 0.01). APAO measurements showed a linear positive correlation with age (r = 0.435, p < 0.01), BMI (r = 0.505, p < 0.01), WC (r = 0.487, p < 0.01), triglycerides (r = 0.280, p < 0.01), C-reactive protein (r = 0.209, p < 0.05), fasting insulin (r = 0.378, p < 0.01) and HOMA index (r = 0.345, p < 0.01). FMD was inversely related to age (r = − 0.251, p < 0.01), rough BMI (r = − 0.318, p < 0.01), WC (r = − 0.340, p < 0.01), fasting insulin (r = − 0.281, p < 0.01) and HOMA index (r = − 0.282, p < 0.01). Multiple regression analysis found no influence of HOMA index on APAO and cIMT. HOMA index was an independent predictor for brachial artery FMD worsening after the statistical adjustment.

Conclusion

HOMA index increase induced a worsening in endothelial function since childhood.     

Risk of comorbidities and outcomes in patients with lower gastrointestinal bleeding-a nationwide study

Background

The impact of comorbidities on outcomes of patients with lower gastrointestinal bleeding (LGIB) remains unknown.

Objective

Investigate the prevalence of comorbidities and impact on outcomes of patients with LGIB.

Methods

The Nationwide Inpatient Sample 2010 was used to identify patients who had a primary discharge diagnosis of LGIB based on International Classification of Diseases, the 9th revision, clinical modification codes. The presence of comorbid illness was assessed using the Elixhauser index. Logistic regression models were used to assess the contributions of the individual Elixhauser comorbidities to predict in-hospital mortality.

Results

A total of 58,296 discharges with LGIB were identified. The overall mortality was 2.3 %. Among the patients who underwent colonoscopy, 17.3 % of patients had therapeutic intervention. As the number of comorbidities increased (i.e., 0, 1, 2, or >3), mortality increased (1.7, 2.0, 2.4, and 2.4 %, respectively). The mortality rate was highest in patients >65 years of age (2.7 %). Patients >65 years of age with two or more comorbidities had a mortality rate of 5 % as compared to 2.6 % in those with less than two comorbidities. Congestive heart failure (odds ratio, 1.67 [95 % confidence interval, 1.48–1.95]), liver disease (2.64 [1.83–3.80]), renal failure (1.99 [1.70–2.33]), and weight loss (2.66 [2.27–3.12]) were associated with a significant increase in mortality rate. Comorbidities increased hospital stay and costs.

Conclusions

Comorbidities were associated with increased the risk of mortality and health care utilization in patients with LGIB. Identification of comorbidities and development of risk-adjustment tools may improve the outcome of patients with LGIB.     

Evaluation of four comorbidity indices and Charlson comorbidity index adjustment for colorectal cancer patients

Introduction

Cancer survival is related not only to primary malignancy but also to concomitant nonmalignant diseases. The aim of this study was to investigate the prognostic capacity of four comorbidity indices [the Charlson comorbidity index (CCI), the Elixhauser method, the National Institute on Aging (NIA) and National Cancer Institute (NCI) comorbidity index, and the Adult Comorbidity Evaluation-27 (ACE-27)] for both cancer-related and all-cause mortality among colorectal cancer patients. A modified version of the CCI adapted for colorectal cancer patients was also built.

Methods

The study population comprised 468 cases of colorectal cancer diagnosed between 1 January 2000 and 31 December 2010 at a community hospital. Data were prospectively collected and abstracted from patients’ clinical records. Kaplan-Meier method and multivariate logistic regression models were performed for survival and risk of death analysis.

Results

Only moderate or severe renal disease [hazard ratio (HR) 2.71, 95 % confidence interval (CI) 1.11–6.63] and AIDS (HR 3.27, 95 % CI 1.23–8.68) were independently associated with cancer-specific mortality, with a population attributable risk of 5.18 and 4.36 %, respectively. For each index, the highest comorbidity burden was significantly associated with poorer overall survival (NIA/NCI: HR 2.14, 95 % CI 1.14–4.01; Elixhauser: HR 1.98, 95 % CI 1.09–1.42; ACE-27: HR 1.78, 95 % CI 1.07–1.23; CCI: HR 1.68, 95 % CI 1.05–1.42) and cancer-specific survival. The modified version of the CCI resulted in a higher predictive power compared with other indices studied (cancer-specific mortality HR?=?2.37, 95 % CI 1.37–4.08).

Conclusions

The comorbidity assessment tools provided better prognostic prevision of prospective outcome of colorectal cancer patients than single comorbid conditions.     

The meninges enhance leukaemia survival in cerebral spinal fluid

Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukaemia (ALL) despite current CNS-directed therapies that are also associated with significant short- and long-term toxicities. Herein, we showed that leukaemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS) and increased cell death in cerebral spinal fluid (CSF) both in vitro and in vivo. However, interactions between leukaemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukaemia and suggests novel therapeutic approaches for more effectively targeting leukaemia cells in the CNS.     

The Semaphorin 4D-Plexin-B1-RhoA signaling axis recruits pericytes and regulates vascular permeability through endothelial production of PDGF-B and ANGPTL4

Semaphorin 4D (SEMA4D) is a member of a family of transmembrane and secreted proteins that have been shown to act through its receptor Plexin-B1 to regulate axon growth cone guidance, lymphocyte activation, and bone density. SEMA4D is also overexpressed by some malignancies and plays a role in tumor-induced angiogenesis similar to vascular endothelial growth factor (VEGF), a protein that has been targeted as part of some cancer therapies. In an attempt to examine the different effects on tumor growth and vascularity for these two pro-angiogenic factors, we previously noted that while inhibition of both VEGF and SEMA4D restricted tumor vascularity and size, vessels forming under conditions of VEGF blockade retained their association with pericytes while those arising in a background of SEMA4D/Plexin-B1 deficiency did not, an intriguing finding considering that alteration in pericyte association with endothelial cells is an emerging aspect of anti-angiogenic intervention in the treatment of cancer. Here we show through array analysis, immunoblots, migration and co-culture assays and VE-cadherin immunohistochemistry that SEMA4D production by head and neck carcinoma tumor cells induces expression of platelet-derived growth factor-B and angiopoietin-like protein 4 from endothelial cells in a Plexin-B1/Rho-dependent manner, thereby influencing proliferation and differentiation of pericytes and vascular permeability, whereas VEGF lacks these effects. These results partly explain the differences observed between SEMA4D and VEGF in pathological angiogenesis and suggest that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of solid tumors.     

Synthesis of diagnostic quality cancer pathology images by generative adversarial networks

Deep learning-based computer vision methods have recently made remarkable breakthroughs in the analysis and classification of cancer pathology images. However, there has been relatively little investigation of the utility of deep neural networks to synthesize medical images. In this study, we evaluated the efficacy of generative adversarial networks to synthesize high-resolution pathology images of 10 histological types of cancer, including five cancer types from The Cancer Genome Atlas and the five major histological subtypes of ovarian carcinoma. The quality of these images was assessed using a comprehensive survey of board-certified pathologists (n = 9) and pathology trainees (n = 6). Our results show that the real and synthetic images are classified by histotype with comparable accuracies and the synthetic images are visually indistinguishable from real images. Furthermore, we trained deep convolutional neural networks to diagnose the different cancer types and determined that the synthetic images perform as well as additional real images when used to supplement a small training set. These findings have important applications in proficiency testing of medical practitioners and quality assurance in clinical laboratories. Furthermore, training of computer-aided diagnostic systems can benefit from synthetic images where labeled datasets are limited (e.g. rare cancers). We have created a publicly available website where clinicians and researchers can attempt questions from the image survey ( http://gan.aimlab.ca/ ). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Treatment of uterine fibromyoma with bilateral uterine artery embolization: state of the art

Uterine fibroids are common tumors of the female pelvis. Uterine artery embolization (UAE) is a minimally invasive alternative procedure in appropriate candidates to conventional myomectomy and hysterectomy for symptomatic uterine leiomyoma, reducing or eliminating leiomyoma-related symptoms of bleeding, bulk, and/or pain. In order to completely block the arterial blood supply to the fibroid, UAE is typically performed in both uterine arteries. At 1 year follow-up, the uterus may shrink by up to 55%, however, a re-growth of the fibroid may occur. The rate of major complications and amenorrhea following this procedure is low, ranging in most series from 1% to 3.5% and 1% to 7%, respectively. Nevertheless, the rate of amenorrhea in women over 45 seems to be higher. Women who wish to become pregnant should be cautioned about potential complications during pregnancy. Despite the lack of controlled studies that compared UAE with conventional surgery, and despite limited extended outcome data, UAE has gained rapid acceptance, primarily because this procedure preserves the uterus, is less invasive, and has less short-term morbidity than most surgical options. This review focuses on recent publications evaluating UAE and concludes that it is a safe treatment option, providing substantial improvement in both health-related quality of life and symptom control for most patients, with a very low rate of major complications. Any centre that offers UAE should adhere to published clinical guidelines, maintain ongoing assessment of quality improvement measures, and observe strict criteria to obtain procedural privileges. The gynecologist is likely to be the primary initial consultant to patients who present with myomas symptoms. Therefore, they must be familiar with the indications, exclusions, outcome expectations, and complications of UAE. When hysterectomy is the only option, UAE should be seriously taken into consideration. At this particular moment in time, data are needed from randomized controlled trials comparing UAE with surgical procedures. Current efforts to provide prospective objective assessment of treatment outcomes and complications after UAE will help to optimize women options and clinical guidelines.