Tobacco, hypertension, and vascular disease: Risk factors for renal functional decline in an older population

Tobacco, hypertension, and vascular disease: Risk factors for renal functional decline in an older population.BackgroundA decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population.MethodsA retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase.ResultsThere was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate “best-fit” model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness.ConclusionsThese data suggest that three very preventable or treatable conditions—hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease—are highly associated with clinically important changes in renal function in an older population

Multiple aneurysms in childhood

AbstractArterial aneurysms in children are rare. When present, they are often associated with connective tissue disorders or arteritidies. Idiopathic aneurysms occurring at multiple sites throughout the arterial tree are rare, with only ten cases reported. This report describes a case of multiple arterial aneurysms of uncertain origin involving upper-extremity, extracranial cerebrovascular, aortoiliac, and renal arteries in a 14-year-old boy. The clinical presentation, vascular reconstruction, pathologic findings, and a brief review of the literature are described

Outcomes of acute intraoperative surgical conversion during endovascular aortic aneurysm repair

PurposeOutcomes and predictors of acute surgical conversion during endovascular aortic aneurysm repair (EVAR) were examined using the American College of Surgeons-National Safety and Quality Improvement Project (ACS-NSQIP) Database (2005 to 2008).MethodsAcute intraoperative surgical conversions occurring during elective EVAR were identified using Current Procedural Terminology codes. Nonemergent EVAR and primary open surgical repairs of infrarenal aneurysms were examined for comparison. Perioperative morbidity was categorized as wound, pulmonary, venous thromboembolic, genitourinary, cardiovascular, operative, and septic. Mortality, overall morbidity, and length of stay (LOS) were examined.ResultsWe identified 72 acute conversions, 2414 open repairs, and 6332 EVAR without acute conversion. Demographics and comorbidities were generally similar among operative groups. Mean operative time was 274 minutes for acute conversion vs 226 minutes for primary open repair and 162 minutes for EVAR (conversion vs EVAR and open repair vs EVAR P < .0001 for each; conversion vs open repair P = .0014; analysis on rank operative time). Blood transfusion was required in 69% of acute conversions (mean volume, 6.0 units) vs 73% of open repairs (mean volume, 3.3 units) and 12% of EVARs (mean volume, 2.6 units; P < .0001 for each pair-wise comparison; analysis on rank number of units among those transfused). Major morbidity was 28% for acute conversions, 28% for open repairs, and 12% for EVARs. Mortality was 4.2% for acute conversions, 3.2% for open repairs, and 1.3% for EVARs. Median (quartile 1, quartile 3) LOS was 7 (5, 9) days for acute conversion and open repair, and 2 (1, 3) days for EVAR. Morbidity and mortality were significantly higher for acute conversion and open repair vs EVAR. The OR (95% confidence interval) for morbidity was 2.9 (1.7-4.8) after conversion and 2.8 (2.5-3.2) after open repair (P < .0001 for both) and for mortality was 3.4 (1.0-10.9; P = .0437) for conversion and 2.5 (1.9-3.5; P < .0001) for open repair. Morbidity and mortality were similar between acute conversion and open repair. A similar pattern among repair groups was demonstrated for LOS, with similar LOS for acute conversions and open repair, which were significantly longer than those observed for EVAR. No significant demographic or medical risk factor predictors of acute conversion during EVAR were identified.ConclusionAcute surgical conversion was a rare complication affecting 1.1% of EVAR cases, with no broadly identifiable at-risk population. When conversion did occur, morbidity and mortality rates paralleled those observed for elective open repair

Survival of young patients after abdominal aortic aneurysm repair

AbstractPurpose: This study assessed the cardiovascular disease, perioperative results, and survival after surgical abdominal aortic aneurysm repair in young patients (≤ 50 years) compared with randomly selected older patients who also underwent abdominal aortic aneurysm repair. Methods: We reviewed hospital records to identify young and randomly selected control patients (3 for each young patient, ≥ 65 years, matched for year of operation) with degenerative (atherosclerotic) abdominal aortic aneurysms undergoing repair between Jan 1, 1988, and Mar 31, 2000. Patients with congenital aneurysms, pseudoaneurysms, aortic dissections, post-coarctation dilations, aortic infection, arteritis, or aneurysms isolated to the thoracic aorta were excluded. Mortality data and cause of death were obtained from medical records and the National Death Index Results: Among 1168 patients who underwent abdominal aortic aneurysm repairs, 19 young patients (1.6%) and 57 control patients were identified. The mean age was 48.4 years in the young group and 72.2 years in the control group. There were no differences in sex or race between the two groups. When comparing existing cardiovascular disease between the groups, there were no differences in the incidence of earlier coronary revascularization (26% vs 16%) or non-cardiac vascular surgery (5% vs 9%), but aneurysms were more commonly symptomatic in young patients (53% vs 21%; P <.01). Aneurysmal disease was limited to the infrarenal aorta in similar proportions of patients (89% vs 88%). No statistically significant differences were seen in the incidence of perioperative deaths (16% young vs 9% control; P =.40) or postoperative complications (37% young vs 26% control; P =.38). The estimated survival rate of the young group was not different from that of the control group (3-year survival rate, 73% vs 69%; P =.32) or the entire cohort of patients (older than 50 years; n = 1101) who underwent repair of abdominal aortic aneurysms during the study period (3-year survival 73% vs 75%; P =.63) Conclusion: After abdominal aortic aneurysm repair, young patients had perioperative results and follow-up mortality rates similar to those of control patients. Cardiovascular disease was the predominant cause of death after abdominal aortic aneurysm repair in the young patients. When compared with an age older than 50 years at the time of abdominal aortic aneurysm repair, young age alone was not associated with increased survival. (J Vasc Surg 2002;35:94-9.

Mesenteric artery disease in the elderly

AbstractPurposeThe purpose of this study was to estimate the population-based prevalence of mesenteric artery stenosis (MAS) and occlusion among independent elderly Americans.MethodAs part of an ancillary investigation to the Cardiovascular Health Study (CHS), participants in the Forsyth County, NC cohort had visceral duplex sonography of the celiac arteries and superior mesenteric arteries (SMAs). Critical MAS was defined by celiac peak systolic velocity ≥2.0 m/s and/or SMA peak systolic velocity ≥2.7 m/s. Occlusion of either vessel was defined by lack of a Doppler-shifted signal within the imaged artery. Demographic data, blood pressures, and blood lipid levels were collected as part of the baseline CHS examination. Participants' weights were measured at baseline and before the duplex exam. Univariate tests of association were performed with two-way contingency tables, Student t tests, and Fisher exact tests. Multivariate associations were examined with logistic regression analysis.ResultsA total of 553 CHS participants had visceral duplex sonography technically adequate to define the presence or absence of MAS. The study group had a mean age of 77.2 ± 4.9 years and comprised 63% women and 37% men. Participant race was 76% white and 23% African-American. Ninety-seven participants (17.5%) had MAS. There was no significant difference in age, race, gender, body mass index, blood pressure, cholesterol, or low-density lipoproteins for participants with or without MAS. Forward stepwise variable selection found renal artery stenosis (P = .008; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.31, 6.21) and high-density lipoprotein >40 (P = .02; OR, 3.03; 95% CI, 1.17, 7.81) significantly associated with MAS in a multivariate logistic regression model. Eighty-three of the 97 participants with MAS (15.0% of the cohort) had isolated celiac stenosis. Seven participants (1.3% of the cohort) had combined celiac and SMA stenosis. Five participants (0.9% of the cohort) had isolated SMA stenosis. Two participants (0.4% of the cohort) had celiac occlusion. Considering all participants with MAS, there was no association with weight change. However, SMA stenosis and celiac occlusion demonstrated an independent association with annualized weight loss (P = .028; OR, 1.54; 95% CI, 1.05, 2.26) and with renal artery stenosis (P =.001; OR, 9.48; 95% CI, 2.62, 34.47).ConclusionThis investigation provides the first population-based estimate of the prevalence of MAS among independent elderly Americans. MAS existed in 17.5% of the study cohort. The majority had isolated celiac disease. SMA stenosis and celiac artery occlusion demonstrated a significant and independent association with weight loss and concurrent renal artery disease

Population-level impact and herd effects following the introduction of human papillomavirus vaccination programmes: updated systematic review and meta-analysis

Background More than 10 years have elapsed since human papillomavirus (HPV) vaccination was implemented. We did a systematic review and meta-analysis of the population-level impact of vaccinating girls and women against human papillomavirus on HPV infections, anogenital wart diagnoses, and cervical intraepithelial neoplasia grade 2+ (CIN2+)to summarise the most recent evidence about the effectiveness of HPV vaccines in real-world settings and to quantify the impact of multiple age-cohort vaccination.Methods In this updated systematic review and meta-analysis, we used the same search strategy as in our previous paper. We searched MEDLINE and Embase for studies published between Feb 1, 2014, and Oct 11, 2018. Studies were eligible if they compared the frequency (prevalence or incidence) of at least one HPV-related endpoint (genital HPV infections, anogenital wart diagnoses, or histologically confirmed CIN2+) between pre-vaccination and post-vaccination periods among the general population and if they used the same population sources and recruitment methods before and after vaccination. Our primary assessment was the relative risk (RR) comparing the frequency (prevalence or incidence) of HPV-related endpoints between the pre-vaccination and post-vaccination periods. We stratified all analyses by sex, age, and years since introduction of HPV vaccination. We used random-effects models to estimate pooled relative risks.Findings We identified 1702 potentially eligible articles for this systematic review and meta-analysis, and included 65 articles in 14 high-income countries: 23 for HPV infection, 29 for anogenital warts, and 13 for CIN2+.After 5\u20138 years of vaccination, the prevalence of HPV 16 and 18 decreased significantly by 83% (RR 0\ub717, 95% CI 0\ub711\u20130\ub725) among girls aged 13\u201319 years, and decreased significantly by 66% (RR 0\ub734, 95% CI 0\ub723\u20130\ub749) among women aged 20\u201324 years. The prevalence of HPV 31, 33, and 45 decreased significantly by 54% (RR 0\ub746, 95% CI 0\ub733\u20130\ub766) among girls aged 13\u201319 years. Anogenital wart diagnoses decreased significantly by 67% (RR 0\ub733, 95% CI 0\ub724\u20130\ub746) among girls aged 15\u201319 years, decreased significantly by 54% (RR 0\ub746, 95% CI 0.36\u20130.60) among women aged 20\u201324 years, and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub753\u20130\ub789) among women aged 25\u201329 years. Among boys aged 15\u201319 years anogenital wart diagnoses decreased significantly by 48% (RR 0\ub752, 95% CI 0\ub737\u20130\ub775) and among men aged 20\u201324 years they decreased significantly by 32% (RR 0\ub768, 95% CI 0\ub747\u20130\ub798). After 5\u20139 years of vaccination, CIN2+ decreased significantly by 51% (RR 0\ub749, 95% CI 0\ub742\u20130\ub758) among screened girls aged 15\u201319 years and decreased significantly by 31% (RR 0\ub769, 95% CI 0\ub757\u20130\ub784) among women aged 20\u201324 years.Interpretation This updated systematic review and meta-analysis includes data from 60 million individuals and up to 8 years of post-vaccination follow-up. Our results show compelling evidence of the substantial impact of HPV vaccination programmes on HPV infections and CIN2+ among girls and women, and on anogenital warts diagnoses among girls, women, boys, and men. Additionally, programmes with multi-cohort vaccination and high vaccination coverage had a greater direct impact and herd effects

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN