Elevated Blood Homocysteine and Risk of Alzheimer's Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies.

OBJECTIVE: To investigate whether high serum homocysteine (Hcy) levels is associated with the risk of developing Alzheimer's disease (AD) by performing a meta-analysis based on updated published data. METHODS: We conducted a comprehensive research using Medline (Pubmed), Scopus, Web of Science and EMBASE databases to identify all prospective studies published any time to July 7, 2020 evaluating the association between elevated Hcy levels and AD risk. RESULTS: From an initial screening of 269 published papers, 9 prospective investigations conducted on a total of 7474 subjects with mean follow-up of 9.5 years (range: 3.7-10) were included in the meta-analysis. Eight seventy-five of these subjects converted to AD. Hcy was significantly higher in these individuals (HRadjusted:1.48, 95% CI:1.23-1.76, I2=65.6%, p<0.0001) compared with who did not convert to AD. There was a significant publication bias (Egger's test, t=6.39, p=0.0003) and this was overcome by the trim and fill method, which allowed to calculate a bias-corrected imputed risk estimate of HRadjusted:1.20, 95% CI:1.01-1.44, Q value=41.92. CONCLUSIONS: The present meta-analysis found that having higher Hcy increases the risk of AD in the elderly and this finding is consistent with the widely suggested role of this non-proteinogenic α-amino acid in AD neurodegeneration.

Dyslipidaemia and mortality in COVID-19 patients: a meta-analysis.

BACKGROUND: The prevalence and prognostic implications of pre-existing dyslipidaemia in patients infected by the SARS-CoV-2 remain unclear. AIM: To assess the prevalence and mortality risk in COVID-19 patients with pre-existing dyslipidaemia. DESIGN: Systematic review and meta-analysis. METHODS: Preferred reporting items for systematic reviews and meta-analyses guidelines were followed in abstracting data and assessing validity. We searched MEDLINE and Scopus to locate all the articles published up to 31 January 2021, reporting data on dyslipidaemia among COVID-19 survivors and non-survivors. The pooled prevalence of dyslipidaemia was calculated using a random-effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random-effect models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Of about 18 studies, enrolling 74 132 COVID-19 patients (mean age 70.6 years), met the inclusion criteria and were included in the final analysis. The pooled prevalence of dyslipidaemia was 17.5% of cases (95% CI: 12.3-24.3%, P < 0.0001), with high heterogeneity (I2 = 98.7%). Pre-existing dyslipidaemia was significantly associated with higher risk of short-term death (OR: 1.69, 95% CI: 1.19-2.41, P = 0.003), with high heterogeneity (I2 = 88.7%). Due to publication bias, according to the Trim-and-Fill method, the corrected random-effect ORs resulted 1.61, 95% CI 1.13-2.28, P < 0.0001 (one studies trimmed). CONCLUSION: Dyslipidaemia represents a major comorbidity in about 18% of COVID-19 patients but it is associated with a 60% increase of short-term mortality risk.

The risk of thrombosis after acute-COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has been associated with coagulation dysfunction which predisposes patients to an increased risk of both venous and arterial thromboembolism, increasing the short-term morbidity and mortality. Current data evidenced that the rate of post-discharge thrombotic events in COVID-19 patients is lower compared to that observed during hospitalization. Rather than 'true thrombotic events', these complications seem more probably 'immunothrombosis' consequent to the recent infection. Unfortunately, the absence of data from randomized controlled trials, large prospective cohorts and ambulatory COVID-19 patients, left unresolved the question regarding the need of post-discharge thromboprophylaxis due to the absence of strong-level recommendations.

In high risk hypertensive subjects with incidental and unilateral renal artery stenosis percutaneous revascularization with stent improves blood pressure control but not glomerular filtration rate.

AIM: In high-risk hypertensive subjects (HTs) with incidental unilateral renal artery stenosis (RAS), the effectiveness of percutaneous revascularization with stent (PR-STENT) on blood pressure (BP) and glomerular filtration rate (GFR) is not established. METHODS: Eighteen HTs aged 65.7 ± 9.2 years with angiographically diagnosed unilateral RAS (≥ 60%) were randomized to receive PR-STENT (N=9) or to NO-STENT (N=9). BP (mercury sphygmomanometer) and GFR (99mTc-DTPA clearances during renal scintigraphy) were evaluated yearly for three years. Echo-Doppler of renal arteries was performed to verify the anatomic patency and flow velocities of the reperfused artery. Analysis of variance compared BP and GFR values changes from baseline to the follow-up; differences for continuous variables were evaluated between groups with the Tukey's post hoc test after adjustment for age, change of BP between baseline and at the follow-up, GFR and body mass index (BMI). RESULTS: Baseline systolic BP and GFR values were not different between groups. The significantly greater GFR increase observed in PR-STENT than in NO-STENT at univariate analysis at the end of follow-up (62.5 ± 19.2 vs. 42.24 ± 17.6, P<0.02) disappeared after adjustment for confounding factors. However, systolic BP remained significantly lower in PR-STENT than in NO-STENT (140.1 ± 4.6 vs. 170.0 ± 8.3, P<0.0001) also after adjustment for age, GFR and BMI. CONCLUSION: PR-STENT reduces systolic BP without improving GFR. Due to the strong association between high BP and renal damage, this study raises the question on whether PR-STENT should be performed in all HTs with unilateral and incidental RAS.

Intracardiac echocardiography-guided atrial septal defect transcatheter closure of a very old surgical residual shunt.

Although some studies have suggested excellent long-term outcome, arrhythmias, pulmonary hypertension, and paradoxical cerebral embolism are mentioned as results of residual shunts in the long-term follow-up after surgical atrial septal defect (ASD) closure at a young age. In cases of previous patch closure, transcatheter repair of residual shunts can be problematic due both to clinical decision-making in the presence of elevated pulmonary pressure and to a very old patch. A 70-year-old woman operated for an ASD with synthetic patch closure when she was 35 years old was referred to our center because of recurrent paroxysmal atrial fibrillation, initially decompensated right heart failure with rest and exercise-induced dyspnea as results of a residual shunt and moderate pulmonary hypertension. Complete right heart catheterization confirmed a mean pulmonary pressure of about 55 mm Hg and a Qp:Qs ratio of 1.78. A mechanical intracardiac echocardiography study with a 9F 9 MHz UltraICE catheter (Boston Scientific Corp.) showed a highly echogenous interatrial patch with a very stiff appearance and a very high residual defect of 8.7 and 11.2 mm on the aortic valve plane and on the four-chamber views, respectively. An occlusion test with a compliant AGA medical balloon demonstrated a decrease in mean pulmonary pressure to 36 mm Hg. A 10 mm Amplatzer's ASD occluder was implanted after a first unsuccessful attempt due to patch stiffness. Three-month echocardiography follow-up demonstrated almost normal pulmonary pressure and only slight dilation of the right chambers. At six-month follow-up, the patient no longer experienced dyspnea. This case demonstrates that transcatheter closure of a residual shunt following surgical ASD repair can be successfully accomplished also in elderly patients with a very old patch and decompensated right heart failure: the balloon occlusion test and intracardiac echocardiography appear to be effective in the operative decision-making process.

[The diagnostic and therapeutic procedures in pulmonary embolism: a survey in the Veneto Region]. / Iter diagnostici e terapeutici nell'embolia polmonare: inchiesta nella Regione Veneto.

BACKGROUND: Pulmonary embolism is one of the most frequent cardiopulmonary diseases, but it is often under- or misdiagnosed. In order to address this issue and to identify flow charts that are commonly used in pulmonary embolism diagnosis and treatment, 191 clinical wards of internal medicine, cardiology, geriatrics, pneumology and intensive care units, located in the Veneto Region, were surveyed. METHODS: An anonymous questionnaire was mailed to each ward in order to collect clinical diagnostic information on all pulmonary embolisms which occurred during 1993. Among the returned questionnaires, 114 (59.6%) had usable information for the analysis. RESULTS: The vast majority of participating centers reported in 1993 less than 10 pulmonary embolism events. No significant differences were observed between internal medicine, geriatrics, pneumology wards and intensive care units. The reported events, however, were slightly higher in the divisions of cardiology with an annual average of 12 events per center. First level diagnostic procedures, such as ECG, chest X-ray and arterial blood gas analysis were chosen and performed in all patients. Interestingly, Doppler echocardiography, which is often not included in official guidelines for pulmonary embolism diagnosis, was performed in 56% of the participating centers. On the contrary, ventilation-perfusion lung scanning, which is considered highly predictive in many diagnostic algorithms, was underutilized (35% perfusion scan, 20% ventilation scan). This underuse was probably due to technical and organizational difficulties. Pulmonary angiography, the most accurate procedure for the diagnosis of pulmonary embolism, was performed in 28% of the patients. During the acute phase, intravenous heparin was commonly used; 91% of patients received the infusion continuously, 4% intermittently. Thrombolysis was performed in 25% of the patients. The preferred drugs were recombinant tissue-plasminogen activator (67%), followed by urokinase (20%) and streptokinase (13%). To start thrombolytic therapy, 20% of the interviewed clinicians considered sufficient the evidence of clinical manifestations of pulmonary embolism confirmed by echocardiographic data. At discharge, prescription of oral anticoagulant drugs was common (78%) for at least 6 months (47%). Standardized procedures for the diagnosis and treatment of pulmonary embolism were already implemented in 13% of the participating centers. CONCLUSIONS: These data suggest a common effort to define unanimous conventional protocols in the management of pulmonary embolism. It should be underlined, however, that a particular attention to the clinical manifestations and a productive collaboration among clinicians with different expertise are required to improve the diagnosis and treatment of pulmonary embolism.

Pulmonary hypertension associated with human immunodeficiency virus infection. Report of two cases and review of the literature.

Recent reports have suggested a possible association between HIV-1 infection and "idiopathic" pulmonary hypertension (PH), but the pathogenetic role of the viral agent has not been fully defined yet. We report the cases of two white males positive for human immunodeficiency virus type 1 (HIV-1) who presented with clinical and hemodynamic diagnosis of pulmonary hypertension. They were heterosexual, non-hemophiliac, heroin abusers with no signs of clinical AIDS. Neither one of the patients had opportunistic lung infections or any other cause of secondary pulmonary hypertension. In one case, peculiar clinical and electrocardiographic features of PH were associated with signs of thrombotic thrombocytopenic purpura (TTP). The association between PH and HIV-1 infection might be explained by a severe alteration of pulmonary endothelial cell homeostasis secondary to HIV-1 viral infection.

[Bolus thrombolysis in pulmonary embolism. Review of experimental and clinical data]. / La trombolisi in bolo nell'embolia polmonare. Rassegna di dati sperimentali e clinici.

Although heparin is the primary drug used to treat pulmonary embolism, its limits include poor prevention of recurrence, and slow and delayed normalization of hemodynamic parameters. Over the past decades, thrombolysis has proved to be the most rapid and effective therapy to normalize hemodynamic parameters and angiographic and scintigraphic indexes of obstruction. Studies conducted up to the present have not, however, demonstrated a significant advantage over heparin with respect to mortality. Moreover, thrombolytic drugs carry a greater risk of hemorrhage than heparin. Various experimental studies have demonstrated that the short-term administration of recombinant tissue plasminogen activator (rt-PA) is more effective and decreases risk of hemorrhage. To our knowledge, only a few uncontrolled clinical studies on bolus thrombolysis with urokinase have been done. Studies comparing a 0.6 mg/Kg bolus of intravenous rt-PA versus the infusion of 100 mg over 2 hours have given conflicting results. Of these, some have demonstrated that bolus administration is safer and more effective while others have provided nearly overlapping results regarding safety and the reduction of pulmonary resistances. One study reports higher mortality in a group receiving 0.6 mg/Kg bolus rt-PA. Until these questions are clarified, administration of thrombolytics in the following doses is advised: streptokinase bolus 250,000 U over 30 min + 100,000 U/hour for 24 hours; urokinase bolus 4400 U/Kg for 10 min + 4400 U/Kg/hour for 12-24 hours; rt-PA 100 mg for 2 hours.

Follow up after spontaneous coronary artery dissection: a report of five cases.

Five cases of spontaneous coronary artery dissection (SCAD) are reported, three in women and two in men (mean age 44 years; range 28-65), all of whom suffered a myocardial infarction. Common risk factors for coronary artery disease were present in the two men; in the female group one patient was taking an oral contraceptive, one was in the postpartum period, and the third was a smoker. Only the three women received intravenous alteplase and their ejection fraction was normal; both men had impaired left ventricular function. Two patients had SCAD of the left anterior descending coronary artery and three of the right coronary artery. Only the two men had angiographic features of coronary atherosclerotic involvement. No patients required surgical revascularisation or percutaneous transluminal coronary angioplasty. At a mean follow up of 27 months (range 6 to 40) all patients were alive and all but one were asymptomatic.

[Post-infarct rupture of the interventricular septum. 2-dimensional, continuous Doppler, pulsed and color-coded echocardiographic evaluation]. / Rottura post-infartuale del setto interventricolare. Valutazione ecocardiografica bidimensionale, Doppler continuo, pulsato e con codice di colori.

Rupture of the interventricular septum is an infrequent but always serious complication of acute myocardial infarction. It requires accurate timely diagnosis to decide the proper treatment and eventual surgical intervention. Echo-color-Doppler-cardiography appears to have such diagnostic capacities. In a total of 403 pts, with acute myocardial infarction we found 7 pts (1.7%) with suspected interventricular septum rupture; 5 with infero-posterior infarction and 2 with an anterior one. In 4 pts shock and death occurred rapidly, 2 pts were submitted to angiography and then to surgery with a good outcome, 1 pt died immediately after surgical repair. Echocardiographic findings were: 1) by 2-D (7 pts), direct visualization of septal rupture in 5/7, all with infero-posterior infarctions; 2) by pulsed wave Doppler (5 pts), detection of a typical systolic turbulence on the right septum in 5/5 pts, 3 with infero-posterior myocardial infarction, 2 with an anterior one; 3) by color Doppler (3 pts), detection of a "mosaic" color-jet expanding into the right ventricle in 3/3 pts, 2 with an anterior and 1 with an infero-posterior myocardial infarction. This technique immediately located two small ruptures which had not been easily detected by pulsed Doppler alone. In conclusion, echocolordopplercardiography appears to be a reliable method for the detection of ventricular septal rupture after myocardial infarction in so timely and accurately a manner as to rule out more aggressive procedures, angiography and surgery.