Quality of Care Among Patients with Diabetes and Cerebrovascular Disease. Insights from The Diabetes Collaborative Registry.

BACKGROUND: Although secondary cardiovascular prevention is a focus among patients with type 2 diabetes (T2D) and coronary artery disease (CAD) or peripheral artery disease (PAD), the application of guideline-recommended therapy in T2D patients and isolated cerebrovascular disease (CeVD) remains unknown. METHODS: In a US outpatient registry, T2D patients with established cardiovascular disease from 2014-2018 were categorized as: isolated CeVD, CeVD plus CAD or PAD, or isolated CAD/PAD. In each group, we determined the proportion with optimal secondary prevention (hemoglobin [Hb]A1C <8%, blood pressure <130/80 mm Hg, use of antithrombotics, use of statins, non-smoking/cessation counseling, and use of glucose-lowering medications with cardioprotective effects (sodium-glucose cotransporter [SGLT]-2 inhibitors, glucagon-like peptide [GLP]-1 receptor agonists, thiazolidinediones [TZDs]). Hierarchical Poisson regression was used to estimate relative rate of achieving each target across groups, adjusted for age and chronic kidney disease (where relevant). RESULTS: Our study included 727,467 T2D outpatients with cardiovascular disease (isolated CeVD [n = 99,777], CeVD plus CAD/PAD [n = 158,361], isolated CAD/PAD [n = 469,329]). Compared with isolated CAD/PAD patients, isolated CeVD patients more often had an HbA1c <8% (adjusted relative risk [aRR] 1.10; 95% confidence interval [CI], 1.08-1.11) but less often had a blood pressure of ≤130/80 mm Hg (aRR 0.93; 95% CI, 0.92-0.94) or were prescribed antithrombotics (0.84; 95% CI, 0.83-0.85), statins (0.86; 95% CI, 0.85-0.87), GLP-1 agonists (0.75; 95% CI, 0.73-0.78), SGLT2 inhibitors (0.73; 95% CI, 0.71-0.76), and TZDs (aRR 0.76; 95% CI, 0.73-0.78). CONCLUSION: Among T2D patients, those with isolated CeVD had the lowest rates of secondary cardiovascular prevention goals attainment. More focus is needed on secondary prevention in patients with CeVD.

Short-term effects of electronic cigarettes on cerebrovascular function: A time course study.

NEW FINDINGS: What is the central question of this study? Acute exposure to electronic cigarettes (Ecigs) triggers abnormal vascular responses in systemic arteries; however, effects on cerebral vessels are poorly understood and time for recovery is not known. We hypothesized that exposure to cigarettes or Ecigs would trigger rapid (<4 h) impairment of the middle cerebral artery (MCA) but that this would resolve by 24 h. What is the main finding and its importance? Cigarettes and Ecigs caused similar degree and duration of MCA impairment. We find it takes ~72 hours after exposure for MCA function to return to normal. This suggests that Ecig use is likely to produce similar adverse vascular health outcomes to those seen with cigarette smoke. ABSTRACT: Temporal influences of electronic cigarettes (Ecigs) on blood vessels are poorly understood. In this study, we evaluated a single episode of cigarette versus Ecig exposure on middle cerebral artery (MCA) reactivity and determined how long after the exposure MCA responses took to return to normal. We hypothesized that cigarette and Ecig exposure would induce rapid (<4 h) reduction in MCA endothelial function and would resolve within 24 h. Sprague-Dawley rats (4 months old) were exposed to either air (n = 5), traditional cigarettes (20 puffs, n = 16) or Ecigs (20-puff group, n = 16; or 60-puff group, n = 12). Thereafter, the cigarette and Ecig groups were randomly assigned for postexposure vessel myography testing on day 0 (D0, 1-4 h postexposure), day 1 (D1, 24-28 h postexposure), day 2 (D2, 48-52 h postexposure) and day 3 (72-76 h postexposure). The greatest effect on endothelium-dependent dilatation was observed within 24 h of exposure (∼50% decline between D0 and D1) for both cigarette and Ecig groups, and impairment persisted with all groups for up to 3 days. Changes in endothelium-independent dilatation responses were less severe (∼27%) and shorter lived (recovering by D2) compared with endothelium-dependent dilatation responses. Vasoconstriction in response to serotonin (5-HT) was similar to endothelium-independent dilatation, with greatest impairment (∼45% for all exposure groups) at D0-D1, returning to normal by D2. These data show that exposure to cigarettes and Ecigs triggers a similar level/duration of cerebrovascular dysfunction after a single exposure. The finding that Ecig (without nicotine) and cigarette (with nicotine) exposure produce the same effects suggesting that nicotine is not likely to be triggering MCA dysfunction, and that vaping (with/without nicotine) has potential to produce the same vascular harm and/or disease as smoking.

Cardioprotective effects of dipeptidyl peptidase-4 inhibitors versus sulfonylureas in addition to metformin: A nationwide cohort study of patients with type 2 diabetes.

AIMS: Cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP4i) versus sulfonylureas (SU) remain controversial in observational studies. This study aimed to evaluate the influence of DPP4i on major adverse cardiovascular events (MACEs), including acute myocardial infarction, cerebrovascular disease, heart failure, cardiogenic shock, malignant dysrhythmia, and revascularisation. MATERIALS AND METHODS: We conducted a nationwide cohort study using claims data from the National Health Insurance in Taiwan from 2007 to 2013. We enrolled type 2 diabetes patients who received DPP4i or SU in addition to metformin. DPP4i users were matched to SU users using propensity scores at a ratio of 1:1. The study outcomes were hospitalisation for MACE, heart failure, acute myocardial infarction, cerebrovascular disease, coronary revascularisation, and hypoglycaemia. RESULTS: There were 37,317 matched pairs of DPP4i and SU users with a mean follow-up of 2.1 years. Compared with SU users, DPP4i users showed a significantly lower risk of hospitalisation for MACE (HR 0.79 [95% CI 0.75-0.82]), heart failure (0.86 [0.79-0.93]), acute myocardial infarction (0.76 [0.68-0.92]), and cerebrovascular disease (0.72 [0.67-0.77]). Both sitagliptin (0.89 [0.85-0.94]) and vildagliptin ([0.77 [0.60-0.99]) showed a significantly lower risk of hospitalisation for MACE, but saxagliptin showed a borderline significantly higher risk of hospitalisation for heart failure (1.59 [1.00-2.55]). CONCLUSIONS: DPP4i showed better cardioprotective effects than SU, especially among patients receiving sitagliptin or vildagliptin.

Potential risks of cardiovascular and cerebrovascular disease and cancer due to cumulative doses received from diagnostic CT scans?

Potential risks from radiation exposure on the development of cardiovascular and cerebrovascular disease are indicated by epidemiological studies. Medical exposures give the largest dose to the population from artificial sources, with cumulative doses from multiple CT scans being significant. Data on doses from scans performed on 12 CT scanners in three hospitals over a period of 5½ years, derived using RadimetricsTMsoftware, have been reviewed for 105 757 patients. Data have been downloaded for heart, brain, thyroid, and effective doses, and cumulative doses analysed using ExcelTMspreadsheets. 2.4% of patients having body CT scans received cumulative doses to the heart over 100 mSv, 9% of whom were under 50 years. 9.6% of patients having head CT scans received cumulative doses to the brain over 100 mSv with 0.08% over 500 mSv from whom 41% were under 50 years, but only 1.3% of patients scanned had thyroid/carotid artery doses over 100 mSv. An approximate evaluation of potential risks from exposures of the heart above 100 mSv and brain over 500 mSv for patients under 60 years would suggest that at most only one patient would demonstrate any excess risk from vascular disease resulting from the exposures. 0.67% of patients scanned received effective doses over 100 mSv, in line with results from European studies, with 8.4% being under 50 years. The application of age and sex specific risk coefficients relating to excess cancer incidence suggests that two or three patients with effective doses over 100 mSv and five patients with effective doses between 50 and 100 mSv, from those examined, might develop cancer as a result of exposure. However, this will be an overestimate, since it does not take patients' health into account. Exposure management software can aid in evaluating cumulative doses and identifying individual patients receiving substantial doses from repetitive imaging.

Adverse Cerebral Cardiovascular Events Associated With Checkpoint Kinase 1 Inhibitors: A Systemic Review.

ABSTRACT: Checkpoint kinase 1 (CHK1) plays a broad role in regulating the cell cycle process and is involved in the pathogenesis of various malignant tumors. Preclinical and animal studies have shown that CHK1 inhibitors can enhance the cytotoxic effects of radiotherapy and chemotherapy. Currently, CHK1 inhibitors are actively tested in clinical trials. Nonspecific adverse cerebral cardiovascular events were reported after CHK1 inhibitor use; these events need to be monitored and managed carefully during the clinical application of CHK1 inhibitors. To get a better understanding of these, noteworthy adverse cardiovascular events, we systemically searched the PubMed, Cochrane databases, and clinicaltrials.gov, for relevant clinical trials and case reports. A total of 19 studies were identified and included in this review. Among the reported cerebral cardiovascular events, the most common is incident abnormal blood pressure fluctuations (n = 35), followed by incident QTcF prolongation (n = 15), arrhythmia (n = 13, 3 atrial fibrillation and 10 bradycardia), thromboembolic events (n = 9, 6 pulmonary embolisms, 2 stroke, and 1 cerebrovascular event), cardiac troponin T elevation (n = 2), and ischemic chest pain (n = 2). Besides, the estimated incidence for overall cardiovascular events based on the available data is 0.292 (95% confidence interval: 0.096-0.488). CHK1 inhibitors administered in tumor patients on top of conventional therapies can not only enhance the antitumor effects, but also induce adverse cerebral cardiovascular events. It is, therefore, of importance to carefully monitor and manage the CHK1 inhibitor-induced adverse effects on the cerebral cardiovascular system while applying CHK1 inhibitors to tumor patients.

Aldosterone antagonists for people with chronic kidney disease requiring dialysis.

BACKGROUND: People with chronic kidney disease (CKD) requiring dialysis are at a particularly high risk of cardiovascular death and morbidity. Several clinical studies suggested that aldosterone antagonists would be a promising treatment option for people undergoing dialysis. However, the clinical efficacy and potential harm of aldosterone antagonists for people with CKD on dialysis has yet to be determined. OBJECTIVES: This review aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in people with CKD requiring haemodialysis (HD) or peritoneal dialysis (PD). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 5 August 2020 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs), cross-over RCTs, and quasi-RCTs (where group allocation is by a method that is not truly random, such as alternation, assignment based on alternate medical records, date of birth, case record number, or other predictable methods) that compared aldosterone antagonists with placebo or standard care in people with CKD requiring dialysis. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias for included studies. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I² statistic to measure heterogeneity among the studies in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes, or standardised mean differences (SMD) if different scales were used, with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. MAIN RESULTS: We included 16 studies (14 parallel RCTs and two cross-over RCTs) involving a total of 1446 participants. Thirteen studies compared spironolactone to placebo or standard care and one study compared eplerenone to a placebo. Most included studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists probably reduced the risk of death (any cause) for people with CKD requiring dialysis (9 studies, 1119 participants: RR 0.45, 95% CI 0.30 to 0.67; I² = 0%; moderate certainty of evidence). Aldosterone antagonist probably decreased the risk of death due to cardiovascular disease (6 studies, 908 participants: RR 0.37, 95% CI 0.22 to 0.64; I² = 0%; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 studies, 328 participants: RR 0.38, 95% CI 0.18 to 0.76; I² = 0%; moderate certainty of evidence). While aldosterone antagonists probably increased risk of gynaecomastia compared with control (4 studies, 768 participants: RR 5.95, 95% CI 1.93 to 18.3; I² = 0%; moderate certainty of evidence), aldosterone antagonists may make little or no difference to the risk of hyperkalaemia (9 studies, 981 participants: RR 1.41, 95% CI 0.72 to 2.78; I² = 47%; low certainty of evidence). Aldosterone antagonists had a marginal effect on left ventricular mass among participants undergoing dialysis (8 studies, 633 participants: SMD -0.42, 95% CI -0.78 to 0.05; I² = 77%). In people with CKD requiring dialysis received aldosterone antagonists compared to control, there were 72 fewer deaths from all causes per 1000 participants (95% CI 47 to 98) with a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 10 to 21) and for gynaecomastia were 26 events per 1000 participants (95% CI 15 to 39) with a number need to treat for an additional harmful outcome (NNTH) of 38 (95% CI 26 to 68). AUTHORS' CONCLUSIONS: Based on moderate certainty of the evidence, aldosterone antagonists probably reduces the risk of all-cause and cardiovascular death and probably reduces morbidity due to cardiovascular and cerebrovascular disease in people with CKD requiring dialysis. For the adverse effect of gynaecomastia, the risk was increased compared to control. For this outcome, the absolute risk was lower than the absolute risk of death. It is hoped the three large ongoing studies will provide better certainty of evidence.

Risk of Systemic Adverse Events after Intravitreal Bevacizumab, Ranibizumab, and Aflibercept in Routine Clinical Practice.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy plays a central role in the management of neovascular age-related macular degeneration (nAMD), diabetic retinal disease (DRD), and retinal venous occlusive disease (RVO). Within clinical trials, rates of systemic serious adverse events (SAEs) after anti-VEGF treatment have been low. However, the comparative systemic safety profile of common anti-VEGF agents remains incompletely understood. The goal of this study was to compare the systemic safety of intravitreal bevacizumab, ranibizumab, and aflibercept in real-world practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Using a large U.S. administrative claims database of commercially insured and Medicare Advantage enrollees, we identified adult cohorts receiving initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018. We included patients with 1 year of insurance coverage before initial treatment. METHODS: We compared predefined systemic outcomes between anti-VEGF agents occurring within 180 days of treatment initiation using propensity score-weighted Cox proportional hazards models. Patients were censored upon treatment with a different anti-VEGF medication or termination of health plan coverage. MAIN OUTCOME MEASURES: Primary outcomes were acute myocardial infarction (MI), acute cerebrovascular disease (CVD), major bleeding, and all-cause hospitalization. RESULTS: A total of 87 844 patients received initial anti-VEGF injections for nAMD, DRD, and RVO between January 1, 2007, and June 30, 2018 (69 007 bevacizumab; 10 895 ranibizumab; 7942 aflibercept). Postinjection 180-day event rates per 100 patients for MI, CVD, major bleeding, and all-cause hospitalization were similar for bevacizumab (0.64, 0.59, 0.34, and 10.41, respectively), ranibizumab (0.62, 0.53, 0.40, and 9.44, respectively), and aflibercept (0.63, 0.60, 0.20, and 9.88, respectively). No differences were identified for the risk of MI, CVD, major bleeding, or all-cause hospitalization when comparing the risk-adjusted effect of treatment initiation with bevacizumab versus ranibizumab (hazard ratio [HR], 0.96 [95% confidence interval {CI}, 0.74-1.25]; HR, 1.04 [95% CI, 0.78-1.38]; HR, 0.85 [95% CI, 0.61-1.19]; HR, 1.03 [95% CI, 0.96-1.10], all P > 0.05), bevacizumab versus aflibercept (HR, 0.95 [95% CI, 0.68-1.33], HR, 0.99 [95% CI, 0.71-1.38], HR, 1.02 [95% CI, 0.60-1.74], HR, 1.01 [95% CI, 0.93-1.10], all P > 0.05), or aflibercept versus ranibizumab (HR, 0.91 [95% CI, 0.62-1.35], HR, 1.12 [95% CI, 0.74-1.69], HR, 0.96 [95% CI, 0.53-1.73], HR, 1.02 [95% CI, 0.92-1.13], all P > 0.05). CONCLUSIONS: We observed no differences in the risk of acute MI, CVD, major bleeding, or all-cause hospitalization after treatment initiation with intravitreal bevacizumab, ranibizumab, or aflibercept during routine clinical practice.

Safety of Pediatric rhGH Therapy: An Overview and the Need for Long-Term Surveillance.

Growth hormone (GH) therapy dates back to 1958 and, though has shown an excellent safety profile in the short-term, has never ceased to raise concern about potential long-term side effects. In the last decade, a number of observational studies in different cohorts of young adult patients treated with GH during childhood have yielded conflicting results. The attention has mainly focused on three major potential risks associated with GH therapy: cancer, cardio and cerebrovascular diseases and diabetes. This review intends to provide a detailed overview of the main studies reporting long-term safety in subjects treated with rhGH therapy during childhood, highlighting the evidence for or against the risk of cancer, cardio and cerebrovascular diseases and diabetes.

Does androgen-deprivation therapy increase the risk of ischemic cardiovascular and cerebrovascular diseases in patients with prostate cancer? A nationwide population-based cohort study.

PURPOSE: We investigated whether ADT use was associated with the risk of ischemic cardiovascular diseases (CVD) and cerebrovascular diseases (CrVD) in a nationwide population-based cohort. METHODS: Claims data of the Health Insurance and Review Assessment system in South Korea were used. In total, 195,308 men with newly diagnosed prostate cancer between January 1, 2008 and December 31, 2017 were identified. After applying the exclusion criteria, 131,189 men were enrolled. The study cohort was divided into ADT and non-ADT groups. Study outcomes were newly developed CVD, cardiovascular intervention (CVI), and CrVD. To control for potential confounders, various cardiovascular risk factors were balanced between groups. Cox proportional hazard regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of events. RESULTS: Univariable analysis revealed that ADT was significantly associated with an increased risk of CVD and CrVD. Multivariable analysis did not reveal this association. In the propensity score matched cohort (n = 61,722), multivariable analysis demonstrated that ADT independently reduced the risk of CVD (HR 0.890; 95% CI 0.846-0.936; p < 0.0001), CVI (HR 0.873; 95% CI 0.770-0.991; p = 0.0352), and CrVD (HR 0.869; 95% CI 0.824-0.917; p < 0.0001). CVD risk was significantly decreased in patients using ADT for over 2 years. CVI and CrVD risks were significantly lower in men using ADT for over 3 years. CONCLUSION: This study demonstrated that ADT may reduce the risk of CVD, CVI, and CrVD, and ADT duration is associated with this risk reduction.

Achievement of target SBP without attention to decrease in DBP can increase cardiovascular morbidity in treated arterial hypertension: the Campania Salute Network.

OBJECTIVES: Results of the SPRINT study have influenced recent guidelines on arterial hypertension, in the identification of target SBP, but scarce attention has been paid to the consequences on DBP. However, there is evidence that reducing DBP too much can be harmful. METHODS: We analyzed outcome in 4005 treated hypertensive patients (22% obesity, 8% diabetes and 21% current smoking habit) with target attended office SBP less than 140 mmHg, in relation to quintiles of DBP, cardiovascular risk profile and target organ damage (LV hypertrophy, carotid plaque and left atrial dilatation). Composite fatal and nonfatal cardiovascular event was the outcome variable in this analysis (stroke and myocardial infarction, sudden cardiac death, heart failure requiring hospitalization, transient ischemic attack, myocardial revascularization, de novo angina, carotid stenting and atrial fibrillation). RESULTS: Lower DBP was associated with greater proportion of women and diabetes, older age, decline in kidney function and greater values of LV mass index and left atrial volume and greater prevalence of carotid plaque (all 0.04 < P < 0.0001). The lowest quintile of DBP (74.1 ±â€Š3.7 mmHg) was associated with 1.49 higher hazard of composite cardiovascular events, independently of significant effect of older age, female sex, LV hypertrophy and borderline effect of left atrial dilatation (0.04 < P < 0.001). CONCLUSION: Increased risk associated with aggressive reduction of DBP should be balanced with the advantage of reducing aggressively SBP to predict the net benefit of antihypertensive treatment, especially in the oldest old individuals.

Elevated Presepsin Is Associated With Perioperative Major Adverse Cardiovascular and Cerebrovascular Complications in Elevated-Risk Patients Undergoing Noncardiac Surgery: The Leukocytes and Cardiovascular Perioperative Events Study.

BACKGROUND: Perioperative major adverse cardiovascular and cerebrovascular events (MACCEs) are incompletely understood, and risk prediction is imprecise. Atherogenic leukocytes are crucial in cardiovascular events. However, it is unclear if surgical interventions affect leukocyte counts or activation status. Therefore, we investigated whether noncardiac surgery in patients with elevated cardiovascular risk is associated with changes in atherogenic leukocyte subsets and if these changes are related to perioperative MACCEs. METHODS: We enrolled 40 patients in this single-center prospective observational cohort study. Total leukocytes and subpopulations, including classical, intermediate, and nonclassical monocytes and natural killer and regulatory T cells, were quantified before surgery, at 2 and 6 hours after skin incision, and at postoperative days 1 and 2 (POD1+2). The monocyte activation marker presepsin (sCD14-ST) was measured post hoc to determine differentiation of classical to nonclassical monocytes. We evaluated presepsin for prediction of the composite primary end point MACCE (cardiovascular death, myocardial infarction, myocardial ischemia, and stroke) at 30 days. Its additive value to risk assessment based on high-sensitive cardiac troponin T and N-terminal probrain natriuretic peptide (NT-proBNP) was analyzed. RESULTS: We evaluated 38 patients, of whom 5 (13%) reached MACCE. In the entire cohort, classical monocytes continuously increased and peaked at POD1 (0.35 [0.23-0.43] cells per nanoliter blood [nL] vs 0.45 [0.31-0.66] cells·nL, preoperative [pre-OP] vs POD1, P = .002). Intermediate monocytes doubled by POD1 (0.017 [0.013-0.021] vs 0.036 [0.022-0.043] cells·nL, pre-OP versus POD1, P = .0003). Nonclassical monocytes decreased (0.022 [0.012-0.032] vs 0.012 [0.005-0.023] cells·nL, pre-OP vs 6 hours, P = .003). In our patient population, we did not detect changes in any of the other predefined leukocyte subsets investigated. In patients experiencing a MACCE, classical monocyte expansion was reduced (0.081 [-0.16 to 0.081] cells·nL vs 0.179 [0.081 to 0.292] cells·nL, MACCE versus non-MACCE, P = .016). Patients in the event group presented with elevated pre-OP presepsin (1528 [406-1897] pg·mL vs 123 [82.2-174] pg·mL, MACCE versus non-MACCE, P = .0001). Presepsin was associated with MACCE (area under the curve = 0.964, [0.846-0.998], P = .001). Presepsin above the calculated threshold >184 pg·mL was superior to high-sensitive cardiac troponin T for improvement of NT-proBNP-based risk prediction (28 [74%] vs 22 [58%] correctly classified patients, P = .014). CONCLUSIONS: Noncardiac surgery was associated with an increase in atherogenic leukocyte subsets. In a post hoc analysis, elevated pre-OP presepsin was associated with MACCE and improved NT-proBNP-based risk assessment. After validation in an independent data set, a presepsin cutoff of 184 pg·mL might qualify to complement NT-proBNP-based risk prediction, thereby increasing the proportion of correctly identified high-risk patients.

[Reversible cerebral vasoconstriction syndrome associated with anastrozole: an unusual cause of high impact]. / Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is a low incidence disability with a multifactorial etiology and a wide array of symptoms. The main symptom is a thunderclap headache, accompanied sometimes with various neurological deficits that can lead to death. RCVS is usually diagnosed through radiological imaging technology. The treatment includes adopting general measures of monitoring, symptomatic management, identifying the etiology and acting on it to avoid recurrence. CASE REPORT: A 71-year-old woman with a history of breast cancer originally treated with tamoxifen. Due to urticaria, the anastrozole management was staggered. She was admitted for aphasia, drowsiness and a thunderclap headache. The patient reported a similar event two weeks prior admission. In brain resonance, there was evidence of small sub-arachnoidal haemorrhage (SAH) of the left parietal temporal convexity and cerebral angiography. As well as documented vasospasm in the posterior parietal region confirming the diagnosis of RCVS plus SAH. During the stay, she presented three events with the same characteristics, requiring intensive monitoring and two therapeutic panangiographies with intra-arterial nimodipine with subsequent resolution of the vessel spasm. The patient remains asymptomatic six months later. CONCLUSION: RCVS is difficult to diagnose given its wide array of symptoms and multifactorial etiology. In this case, RCVS plus SAH is associated with the use of anastrozole. So far there are no reported cases of aromatase inhibitors associated with this pathology and should be reported in the literature for pharmacovigilance.

TITLE: Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.Introduccion. El sindrome de vasoconstriccion cerebral reversible (SVCR) es una entidad de baja incidencia, de etiologia multifactorial y amplio espectro de presentacion. El principal sintoma es la cefalea de tipo trueno. Puede estar acompañado de focalizacion neurologica y cursar con desenlaces clinicos variable que incluso pueden llevar a la muerte. El diagnostico es clinico e imaginologico, y el tratamiento incluye adoptar medidas generales de monitorizacion, manejo sintomatico, identificar la etiologia y actuar sobre ella para evitar recurrencia. Caso clinico. Mujer de 71 años con antecedente de cancer de seno, tratada inicialmente con tamoxifeno; por presentar urticaria, se escalono tratamiento con anastrozol. Ingreso por cefalea de tipo trueno, afasia anterior y somnolencia. La paciente refirio un evento similar una semana antes del ingreso. En la resonancia magnetica cerebral evidencio una hemorragia subaracnoidea (HSA) pequeña de la convexidad temporoparietal izquierda, y la panangiografia documento vasoespasmo en la region parietal posterior, lo que confirmo el diagnostico de SVCR mas HSA. Durante el ingreso presento tres eventos de iguales caracteristicas, que requirieron monitorizacion intensiva y dos panangiografias terapeuticas con nimodipino intraarterial, con posterior resolucion del vasoespasmo. Permanece asintomatica seis meses despues. Conclusion. El SVCR constituye un reto diagnostico dada su presentacion variable y su etiologia multifactorial. En este caso, el SVCR mas HSA esta asociado al uso de anastrozol. Hasta el momento no hay casos descritos de inhibidores de la aromatasa asociados a esta patologia, que debe comunicarse para su farmacovigilancia.

Mecanismos de los efectos nocivos para la salud de la contaminación atmosférica proveniente de incendios forestales / Mechanisms of noxious effects of wildfire air pollution over human health

Los incendios forestales representan un problema creciente de la salud pública a nivel mundial, especialmente para la población más vulnerable (niños, ancianos, embarazadas y portadores de enfermedades cardiovasculares o respiratorias crónicas) expuesta al humo y a otros contaminantes aéreos. A diferencia de la contaminación atmosférica habitual de grandes urbes, aquella derivada de los incendios forestales tiene una composición diferente y su ocurrencia es esporádica y difícil de prever. La exposición a contaminantes atmosféricos derivados de incendios forestales se asocia a aumento de la morbilidad respiratoria y cardiovascular, mediada por una respuesta inflamatoria pulmonar y sistémica, estrés oxidativo y disfunción endotelial. En sujetos expuestos a humo de incendios forestales se ha observado un aumento en la producción de citoquinas pro-inflamatorias, activación endotelial y disfunción del sistema nervioso autónomo, que produce daño tisular, aumento de los mecanismos protrombóticos, aumento de la presión arterial y cambios en el ritmo cardiaco. Esta revisión analiza los mecanismos que han sido involucrados en generar efectos nocivos para la salud de seres humanos expuestos a material particulado y gases emanados de incendios forestales.

Wildfires represent a growing global public health issue, especially to the most vulnerable segment of the population (children, old people, pregnant women, patients with cardiovascular or respiratory diseases) exposed to smoke and other air borne contaminants generated from these events. In contrast to great cities ' usual atmospheric pollution, that derives from forest fires differ in composition and its occurrence is sporadic and usually unpredictable. Exposure to atmospheric pollutants derived from forest fires has been associated to increased respiratory and cardiovascular morbidity, mediated by an inflammatory systemic response, oxidative stress and endothelial dysfunction. In people exposed to forest fire smoke an increased production of pro-inflammatory cytokines, endothelial activation and autonomic nervous system dysfunction has been observed, that leads to tissue injury, increased prothrombotic response, increased blood pressure and changes in heart rhythm. This review analyzes the mechanisms that have been involved in generating harmful health effects in humans exposed to inhaled particulate matter and gases steaming from wildfires.

Risk of Systemic Adverse Events Associated with Intravitreal Anti-VEGF Therapy for Diabetic Macular Edema in Routine Clinical Practice.

PURPOSE: Intravitreal anti-vascular endothelial growth factor (VEGF) pharmacotherapy has become standard of care for the management of diabetic macular edema (DME). The systemic safety profile of this treatment in routine clinical practice remains incompletely understood. We used a large claims database to investigate the risk of systemic serious adverse events (SAEs) in patients receiving anti-VEGF for DME compared with controls treated with macular laser photocoagulation or intravitreal corticosteroid. DESIGN: Retrospective cohort study. PARTICIPANTS: By using a large U.S. insurance database, we identified privately insured and Medicare Advantage patients aged ≥18 years treated with anti-VEGF for DME between January 1, 2006, and December 31, 2015, along with control patients receiving macular laser or corticosteroid. We included patients with 1 year of medical coverage before initial DME treatment. METHODS: We assessed associations between treatment modalities and predefined systemic outcomes using Cox proportional hazards regression. We performed 2 separate comparisons, one between anti-VEGF and macular laser and one between anti-VEGF and corticosteroid. We used inverse propensity score weighting for the first comparison to account for treatment selection bias. For the second, we used 2:1 propensity score matching on demographics, year, and baseline comorbidities because of the smaller number of corticosteroid-treated patients. MAIN OUTCOME MEASURES: Risk of cerebrovascular disease, myocardial infarction, major bleeding, and all-cause hospitalization occurring within 6 months of initial DME treatment as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 23 348 patients receiving treatment for DME met inclusion criteria; 13 365 received macular laser, 9219 received intravitreal anti-VEGF, and 764 received intravitreal corticosteroid as initial treatment. Anti-VEGF pharmacotherapy was not associated with an increased hazard of cerebrovascular disease (HR, 0.96; 95% CI, 0.65-1.41; P = 0.83), major bleeding (HR, 1.23; 95% CI, 0.76-1.99; P = 0.41), or myocardial infarction (HR, 1.03; 95% CI, 0.73-1.44; P = 0.88) when compared with macular laser for DME; however, there was an increased hazard of post-treatment all-cause hospital admission (HR, 1.17; 95% CI, 1.05-1.30; P = 0.01). The rates of all primary systemic SAE outcomes were similar after treatment with anti-VEGF versus corticosteroid (P > 0.05 for all). CONCLUSIONS: We identified no increased risk of cerebrovascular disease, myocardial infarction, or major bleeding within 6 months after intravitreal anti-VEGF pharmacotherapy for the treatment of DME in routine clinical practice. A potential difference in all-cause hospitalization may merit further investigation.

Case-control study examining the association between allopurinol use and ischemic cerebrovascular disease.

Few studies focus on the relationship between allopurinol and ischemic cerebrovascular disease. The goal of the study was to investigate the association of long-term therapy of allopurinol with the first-time attack of ischemic cerebrovascular disease in Taiwan. We performed a case-control study using the database of the Taiwan National Health Insurance Program. The case group included 14,937 subjects aged 20-84 years with the first-time attack of ischemic cerebrovascular disease from 2000 to 2013. The control group included 14,937 sex-matched and age-matched subjects aged 20-84 years without any type of cerebrovascular disease. Ever use of allopurinol was defined as subjects who had at least a prescription for allopurinol before the index date. The OR and the 95% CI for ischemic cerebrovascular disease associated with allopurinol use were measured by the multivariable logistic regression model. The adjusted OR of ischemic cerebrovascular disease was 0.992 (95% CI 0.989 to 0.996) for subjects with increasing cumulative duration of allopurinol use for every 1 month, compared with never use. In a further analysis, the adjusted OR of ischemic cerebrovascular disease was 0.74 (95% CI 0.57 to 0.96) for cumulative duration of allopurinol use >3 years, compared with never use. Our findings suggest that lone-term therapy of allopurinol >3 years is associated with decreased risk of the first-time attack of ischemic cerebrovascular disease, compared with no allopurinol therapy.

The burden of cardio-cerebrovascular disease and lung cancer attributable to PM2.5 for 2009, Guangzhou: a retrospective population-based study.

Particulate matter pollution has become a widely-concerned issue in public health and led to a substantial loss of health. The study reports relationship between particulate matter with aerodynamic diameter <2.5 µm (PM2.5) and years of life lost (YLL) in Guangzhou. A retrospective burden analysis on annual mean PM2.5 data was conducted. Data on annual mortality were collected for 2009, from the Health Department of Guangzhou. Data on particulate matter were collected for period 2006-2009. Comparative risk assessment and exposure-response function were used to estimate attributable YLL. The exposure to PM2.5 was associated with a total of 454.6 YLLs (95% uncertainty interval 449.0-460.1) per 100,000 people in 2009. This study has confirmed the substantial adverse health effects of PM2.5 exposure in population with cardio-cerebrovascular disease and lung cancer. This study highlights the need to reduce ambient particulate pollution for better environmental health and lower burden of disease.

Tyrosine kinase inhibitor induced rapidly progressive vasculopathy after intracranial stent placement.

Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) has been associated with progressive peripheral arterial disease and, more recently, rare cases of intracranial vascular stenosis have been reported. We report the fourth case of TKI treatment associated intracranial vasculopathy and rapid progression of intracranial vascular stenosis following intracranial stent placement. This was a 49-year-old woman who developed right-sided weakness, paresthesias, numbness, and speech difficulties 7 years following TKI treatment for CML. Cerebral catheter angiography demonstrated 90% stenosis of the left supraclinoid internal carotid artery, for which the patient underwent intracranial stent placement with no residual stenosis and improved distal blood flow. Approximately 1 month following the procedure, the patient returned with similar symptoms. Catheter angiography demonstrated 70% and 50% stenosis just distal and proximal to the stent construct, respectively. Rapid disease progression and non-atherosclerotic vasculopathy may argue against endovascular therapy.

Tyrosine kinase inhibitor induced rapidly progressive vasculopathy after intracranial stent placement.

Tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) has been associated with progressive peripheral arterial disease and, more recently, rare cases of intracranial vascular stenosis have been reported. We report the fourth case of TKI treatment associated intracranial vasculopathy and rapid progression of intracranial vascular stenosis following intracranial stent placement. This was a 49-year-old woman who developed right-sided weakness, paresthesias, numbness, and speech difficulties 7 years following TKI treatment for CML. Cerebral catheter angiography demonstrated 90% stenosis of the left supraclinoid internal carotid artery, for which the patient underwent intracranial stent placement with no residual stenosis and improved distal blood flow. Approximately 1 month following the procedure, the patient returned with similar symptoms. Catheter angiography demonstrated 70% and 50% stenosis just distal and proximal to the stent construct, respectively. Rapid disease progression and non-atherosclerotic vasculopathy may argue against endovascular therapy.

[Reversible cerebral vasoconstriction syndrome following smoking cessation and treatment with bupropion]. / Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.

TITLE: Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.

Relationship Between Antipsychotic Medications and Cerebrovascular Disease in Patients With Serious Mental Illness.

INTRODUCTION AND OBJECTIVES: Cerebrovascular disease (CVD), especially in its asymptomatic forms, is relatively common in patients with serious mental illness (SMI). Nevertheless, the literature on this topic is scarce and sometimes contradictory. Antipsychotic medications, especially atypical agents, play an important role in the overall cardiovascular health of these patients. The goal of this study was to analyze the frequency of CVD in patients with and without SMI. PATIENTS AND METHODS: This retrospective cohort study compared the frequency of CVD, including silent forms, in a group of patients without mental illness and without a history of taking antipsychotic medication, with another group of patients diagnosed with SMI who had received antipsychotic treatment. The 2 groups were matched for age and sex, and the mean age of the subjects in the 2 groups was 63 years. RESULTS: The frequency of CVD was the same in both groups and it was not modified by the use of antipsychotic medications. A nonsignificant trend toward an association between CVD and prolonged use of antipsychotic polypharmacy was found. CONCLUSIONS: In this study, in contrast to previous reports, use of antipsychotic medications and the presence of SMI were not associated with an increased risk of CVD.