Cardiovascular complications related to cocaine use: case report

BACKGROUND AND OBJECTIVES: Cocaine is the most commonly used illicit drug and its acute and chronic effects are related to a variety of physiological changes, mainly in the cardiovascular system. This study is a case report of a patient with cardiomyopathy related to cocaine use. CASE REPORT: A 19 year old men, who has been using cocaine and crack since 15 years old, was admitted to the emergency department (ED) in February 2006 with progressive dyspnea during minimal efforts and bloody expectoration. During the physical exam it was observed legs edema, jugular stasis and dyspnea at rest. The echocardiogram demonstrated left ventricular hypocinesia, a 17 mm ventricular thrombus and a 12% ejection fraction. A bleeding from the left upper lobe was identified during a pulmonary bronchoscopy which was treated with arterial embolization. After 48h of the procedure, the patient was asymptomatic and an antithrombotic treatment with warfarin and enoxaparin was started. No obstruction was found at the cineangiography and the patient was discharged after clinical improvement. The patient was admitted again to the intensive care unit in July with intense chest pain and dyspnea at rest. A new cineangiography was performed and it was observed occlusion in the anterior descendent coronary artery. CONCLUSIONS: The cocaine acute effects are commonly seen at the ED but the chronic effects, as the cardiovascular manifestations, can take longer to be correlated as a side effect of cocaine use. Its prolonged use is related to left ventricular systolic dysfunction due to hypertrophy or myocardial dilation, atherosclerosis, arrhythmias, myocyte apoptosis and sympathetic damage.JUSTIFICATIVA E OBJETIVOS: A cocaína é uma droga ilícita amplamente utilizada e o seu uso tem sido associado a efeitos decorrentes da toxicidade aguda e crônica em praticamente todos os órgãos, particularmente no sistema cardiovascular. Este artigo visou descrever um caso de cardiomiopatia em paciente jovem usuário crônico de cocaína. RELATO DO CASO: Paciente do sexo masculino, 19 anos, usuário de cocaína por inalação e crack desde os 15 anos de idade. Foi internado em fevereiro de 2006 devido a dispnéia progressiva aos mínimos esforços e expectoração sanguinolenta. Ao exame físico apresentava edema nos membros inferiores, estase jugular e dispnéia em repouso. Foram observados no ecocardiograma: dilatação das quatro câmaras cardíacas, com hipocinesia difusa de ventrículo esquerdo (VE), trombo mural em VE de 17 mm e fração de ejeção de 12%. Realizada broncoscopia pulmonar que identificou sangramento em língula ativo, tratado com embolização. Após 48h do procedimento, o paciente manteve-se assintomático e sem expectoração sanguinolenta. Iniciado tratamento antitrombótico com warfarina e enoxaparina. A cineangiocoronariografia não evidenciou lesões obstrutivas e o paciente recebeu alta após melhora clínica. Re-internado em julho de 2006 com dor precordial de forte intensidade e dispnéia de repouso. Nova cineangiocoronariografia evidenciou oclusão de terço médio da artéria descendente anterior. CONCLUSÕES: Os efeitos agudos da cocaína freqüentemente motivam atendimento de emergência. Já as suas manifestações crônicas, como as doenças cardiovasculares, podem produzir alterações de difícil correlação futura ao seu consumo prévio. O uso prolongado da cocaína está relacionado à alteração da função sistólica ventricular esquerda por hipertrofia ou dilatação miocárdica, aterosclerose, disritmias cardíacas, apoptose de cardiomiócitos e lesão simpática.UNIFESPUniversidade São FranciscoUNIFESPSciEL

Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC-based triple-therapies, aHR = 3.56, p = 0.012 for tenofovir-based) and for toxicity (aHR = 5.26, p = 0.030 for ABC-based, aHR = 6.60, p = 0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice

Left Main Compression by a Giant Aneurysm of the Left Sinus of Valsalva: An Extremely Rare Reason for Myocardial Infarction and Cardiogenic Shock

Aneurysms of the sinus of Valsalva are very rare and mostly located in the right coronary sinus. They might course with dyspnea, fatigue, and acute coronary syndromes. We present herein an extremely rare case report of a 61-year-old woman diagnosed with external left main coronary compression by a giant aneurysm of the left sinus of Valsalva, which was successfully managed with percutaneous coronary intervention

Unraveling Slurry Chemistry/Nanoparticle/Polymeric Membrane Adsorption Relevant to Cu Chemical Mechanical Planarization (CMP) Filtration Applications

Due to the emergence of sub-10 nm technologies, next generation slurries have continued to increase in complexity to meet stringent device performance demands. Prior to the chemical mechanical planarization (CMP) process, point-of-use filtration (POU) is implemented in order to limit particle aggregates and ultimately decrease surface defects. This study probes the non-covalent interactions at the interface of a fundamental Cu slurry and a polyamide and polypropylene-based membranes. Results indicate that independent of the membrane used, material removal rate (MRR) showed a subtle decrease as a result of filtration (time and P), demonstrating that the synergistic balance between the nanoparticle and slurry additives is disrupted during the filtration process. Corrosion current measurements (Icorr) decreased by at least 85% post-filtration, indicating a rapid adsorption of glycine to the filter membrane. Regardless of the filter membrane, glycine adsorption was further validated using a modified electrochemical quartz crystal nanobalance (EQCN) technique. Since Cu-glycine complexes are integral in controlling MRR, a widely reported method of tracking ∗OH production was employed. Results show a decrease in the concentration of ∗OH, which in turn can be correlated to a decrease in the Cu-glycine complexes, altering the overall Cu MRR

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74–0.83) in the overall population, 0.74 (0.62–0.85) at internal validation and 0.71 (0.62–0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance

Impact of complete revascularization on development of heart failure in patients with acute coronary syndrome and multivessel diseas. a subanalysis of the CORALYS registry

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome

Homeodomain Interacting Protein Kinase 2 Activation Compromises Endothelial Cell Response to Laminar Flow: Protective Role of p21waf1,cip1,sdi1

BACKGROUND: In the cardiovascular system, laminar shear stress (SS) is one of the most important source of endothelial protecting signals. Physical and chemical agents, however, including ionising radiations and anticancer drugs, may injure endothelial cells determining an increase in oxidative stress and genotoxic damage. Whether the SS protective function remains intact in the presence of strong oxidants or DNA damage is currently unclear. METHODS AND RESULTS: To investigate this aspect a series of experiments were performed in which HUVEC were exposed to sub-lethal doses of the radio-mimetic compound Bleomycin (Bleo; 10 microg/ml) which generated free radicals (ROS) without significantly compromising cell survival. Remarkably, the application of a SS of 12 dyne/cm(2) did not protect endothelial cells but markedly accelerated apoptosis compared to controls kept in static culture and in the presence of Bleo. Experiments with the inducible nitric oxide synthase (iNOS) inhibitor GW274150 significantly reduced the SS-dependent apoptosis indicating that the production of NO was relevant for this effect. At molecular level, the ataxia-telangectasia-mutated (ATM) kinase, the homeodomain-interacting protein kinase-2 (HIPK2) and p53 were found activated along a pro-apoptotic signalling pathway while p21(waf1,cip1,sdi1) was prevented from its protective action. RNA interference experiments revealed that HIPK2 and p53 were both important for this process, however, only the forced expression p21(waf1,cip1,sdi1) fully restored the SS-dependent pro-survival function. CONCLUSIONS: This study provides the first evidence that, in the presence of genotoxic damage, laminar flow contributes to endothelial toxicity and death and identifies molecular targets potentially relevant in endothelial dysfunction and cardiovascular disease pathogenesis

Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection?

Background: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 > 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals