Lung Ultrasonography for the Diagnosis of SARS-CoV-2 Pneumonia in the Emergency Department.

STUDY OBJECTIVE: Accurate diagnostic testing to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical. Although highly specific, SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) has been shown in clinical practice to be affected by a noninsignificant proportion of false-negative results. This study seeks to explore whether the integration of lung ultrasonography with clinical evaluation is associated with increased sensitivity for the diagnosis of coronavirus disease 2019 pneumonia, and therefore may facilitate the identification of false-negative SARS-CoV-2 RT-PCR results. METHODS: This prospective cohort study enrolled consecutive adult patients with symptoms potentially related to SARS-CoV-2 infection who were admitted to the emergency department (ED) of an Italian academic hospital. Immediately after the initial assessment, a lung ultrasonographic evaluation was performed and the likelihood of SARS-CoV-2 infection, based on both clinical and lung ultrasonographic findings ("integrated" assessment), was recorded. RT-PCR SARS-CoV-2 detection was subsequently performed. RESULTS: We enrolled 228 patients; 107 (46.9%) had SARS-CoV-2 infection. Sensitivity and negative predictive value of the clinical-lung ultrasonographic integrated assessment were higher than first RT-PCR result (94.4% [95% confidence interval {CI} 88.2% to 97.9%] versus 80.4% [95% CI 71.6% to 87.4%] and 95% [95% CI 89.5% to 98.2%] versus 85.2% [95% CI 78.3% to 90.6%], respectively). Among the 142 patients who initially had negative RT-PCR results, 21 tested positive at a subsequent molecular test performed within 72 hours. All these false-negative cases were correctly identified by the integrated assessment. CONCLUSION: This study suggests that, in patients presenting to the ED with symptoms commonly associated with SARS-CoV-2 infection, the integration of lung ultrasonography with clinical evaluation has high sensitivity and specificity for coronavirus disease 2019 pneumonia and it may help to identify false-negative results occurring with RT-PCR.

Silent cerebrovascular damage and its early correlates in essential hypertensive patients.

This study tested the association between cognitive functions, cerebrovascular damage, and cerebrovascular reactivity in 71 essential young hypertensives (age matched) and 22 normotensives (age matched). They underwent ambulatory blood pressure monitoring, neurocognitive tests, cerebral magnetic resonance, and transcranial Doppler. Twenty-three percent of patients showed more than 10 white matter lesions and 8% showed none. No control subjects showed more than 10 white matter lesions and 90% of normal controls showed no lesions. Patients with more than 10 white matter alterations had longer hypertensive story and showed significant lower nocturnal blood pressure fall. Pulsatility index was correlated with the number of white matter lesions.

Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: a randomized controlled trial.

AIMS: Although acute decompensated heart failure (ADHF) is a common cause of dyspnoea, its diagnosis still represents a challenge. Lung ultrasound (LUS) is an emerging point-of-care diagnostic tool, but its diagnostic performance for ADHF has not been evaluated in randomized studies. We evaluated, in patients with acute dyspnoea, accuracy and clinical usefulness of combining LUS with clinical assessment compared to the use of chest radiography (CXR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in conjunction with clinical evaluation. METHODS AND RESULTS: This was a randomized trial conducted in two emergency departments. After initial clinical evaluation, patients with acute dyspnoea were classified by the treating physician according to presumptive aetiology (ADHF or non-ADHF). Patients were subsequently randomized to continue with either LUS or CXR/NT-proBNP. A new diagnosis, integrating the results of both initial assessment and the newly obtained findings, was then recorded. Diagnostic accuracy and clinical usefulness of LUS and CXR/NT-proBNP approaches were calculated. A total of 518 patients were randomized. Addition of LUS had higher accuracy [area under the receiver operating characteristic curve (AUC) 0.95] than clinical evaluation alone (AUC 0.88) in identifying ADHF (P < 0.01). In contrast, use of CXR/NT-proBNP did not significantly increase the accuracy of clinical evaluation alone (AUC 0.87 and 0.85, respectively; P > 0.05). The diagnostic accuracy of the LUS-integrated approach was higher then that of the CXR/Nt-proBNP-integrated approach (AUC 0.95 vs. 0.87, p < 0.01). Combining LUS with the clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to 2.42 cases/100 patients in the CXR/Nt-proBNP group. CONCLUSION: Integration of LUS with clinical assessment for the diagnosis of ADHF in the emergency department seems to be more accurate than the current diagnostic approach based on CXR and NT-proBNP.

Hypertension and cognitive function.

Arterial hypertension, cerebrovascular disease, and dementia are related pathologies. This paper has reviewed comparatively the incidence of arterial hypertension and adult-onset dementia disorders. Hypertension is associated with cerebrovascular disease, which is in turn associated with dementia. It is the most important modifiable risk factor for stroke, which is a recognized cause of vascular dementia. In terms of pathophysiology of hypertensive brain damage, several hypotheses were developed, such as that vascular alterations induced by hypertension can induce lacunar or cortical infarcts and leucoaraiosis, that hypertension is responsible for cerebrovascular disease and acts into the contest of a pre-existing subclinic Alzheimer's disease (AD), that hypertension determines neurobiologic alterations (such as beta-amyloid accumulation) resulting in neuropathologic damage, and that aging and cerebrovascular risk factors act together to cause cerebral capillary degeneration, mitochondrial disruption, reduced glucose oxidation, and reduced ATP synthesis. The consequence of these alterations are neuronal death and dementia. Macroscopic results of these mechanisms are the so-called white matter lesions (WML), the significance of which is analyzed. Increasing clinical evidence suggests a close relationship between the reduction of elevated blood pressure and countering of both vascular dementia and AD. Antihypertensive treatment probably influences cognitive performances and prevents cognitive function alterations and the development of dementia. It is therefore important to evaluate as soon as possible cognitive functions of hypertensive patients.

Blood pressure in patients with primary aldosteronism is influenced by bradykinin B(2) receptor and alpha-adducin gene polymorphisms.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. PA is most frequently presented as moderate to severe hypertension, but the clinical and biochemical features vary widely. The aim of our study was to identify genetic variants that influence the phenotype of patients with PA. We hypothesized that genetic variants potentially affecting aldosterone production (aldosterone synthase, CYP11B2), renal proximal tubule reabsorption (alpha-adducin), or the mechanisms of counterbalance leading to vasodilatation and sodium excretion (bradykinin B(2)-receptor, B(2)R) could influence the clinical and biochemical characteristics of patients with PA. We studied three polymorphisms of these genes (C-344T of CYP11B2, G460W of alpha-adducin, and C-58T of B(2)R) in 167 primary aldosteronism patients (56 with aldosterone-producing adenoma and 111 with idiopathic hyperaldosteronism). B(2)R and alpha-adducin genotypes were strong independent predictors of both systolic and diastolic blood pressure levels; plasma renin activity and aldosterone also play a marginal role on BP levels. Body mass index, age, sex, and CYP11B2 genotype displayed no significant effect on the clinical parameters of our population. In particular, alpha-adducin and B(2)R polymorphisms accounted for 13.2% and 11.0% of the systolic and diastolic blood pressure variance, respectively. These data suggest that genetic variants of alpha-adducin and the bradykinin B(2)-R influence the blood pressure levels in patients with primary aldosteronism.

[Arterial hypertension and cognitive deficit]. / Ipertensione arteriosa e deficit cognitivo.

Cognitive impairment and dementia are more and more common in the elderly. The first begins, it advances silently and it leads to dementia in few years. Arterial hypertension represents the most important cerebrovascular risk factor after age. In numerous studies an inverse relationship between blood pressure values and cognitive performance emerges: it is possible that arterial hypertension plays a role in the pathogenesis of cognitive decline. Even in asymptomatic subjects the magnetic resonance signs of cerebral damage accompany cognitive impairment development. Antihypertensive therapy influence on cognitive function represents a subject of actual interest. The most studied drugs are calcium antagonists and ACE-inhibitors; they seem to have a protective effect on cognitive impairment, with regard to diuretics and beta-blockers. It would be important to study hypertensive patients, above all young asymptomatic hypertensives, even about cognitive functions, to prevent and consider cognitive decline and effective organ damage.

Hypertension and cerebrovascular damage.

Hypertension is the most important modifiable factor for cerebrovascular disease. Stroke and dementia are growing health problems that have considerable social and economical consequences. Hypertension causes brain lesions by several mechanisms predisposing to lacunar infarctions, leucoaraiosis, and white matter changes as well as to intracerebral haemorrhages. These parenchymal damages determine evident or silent neurological alterations that often precede the onset of cognitive decline. It is important to recognize cerebrovascular disease and, above all, to correlate typical lesions to hypertension. Antihypertensive therapy has shown clinical benefits in primary and secondary prevention of stroke. These drugs represent important instruments against cerebrovascular disease but their effects on cognition are still matter of debate. Cerebral parenchymal and functional damages have to be considered together to make medical intervention more incisive.

Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.

Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was -17%+/-32; atenolol, 62%+/-82; doxazosin, -5%+/-26; fosinopril, -30%+/-24; and irbesartan, -43%+/-27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. beta-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients.

Arterial hypertension: a cause of cognitive impairment and of vascular dementia.

Arterial hypertension is a well-documented modifiable risk factor for cerebrovascular disease and for both cerebral infarction and intracerebral hemorrhage. Recent studies indicate a relationship between high blood pressure in midlife and dementia in late life and suggest that arterial hypertension may represent a cause of vascular dementia (VaD). This paper has reviewed the main evidence of a link between arterial hypertension and vascular cognitive impairment or VaD. Brain lesions induced by hypertension, diagnostic procedures for early diagnosis of vascular cognitive impairment in at risk subjects and the need to include cognitive assessment in patient's general visits in hypertension units are discussed.

Bioequivalence study of nicardipine solution versus nicardipine tablets.

The bioequivalence of a solution (investigational product) and a tablet (reference product) formulation of the dihydropyridine-type derivative Ca2+ antagonist nicardipine were investigated by measuring plasma levels of the compound after single randomized administration of 20 mg of the two formulations. Drugs were given orally in a single dose to 24 healthy volunteers (12 males and 12 females) at the beginning of the experiment and after a two weeks wash-out. Nicardipine is available in oral and intravenous formulations, the second being used for the short-term treatment of hypertensive crises. Oral formulations of nicardipine most diffused include immediate release (20 or 30 mg, three times a day administration), sustained release (30 mg, 45 mg or 60 mg, twice a day administration) and modified release (80 mg, once a day administration) tablets. A nicardipine solution is available only in Spain, but no published studies on the kinetics of this formulation are available. In the last 15 years, the main efforts were aimed to develop sustained or controlled release formulations of nicardipine to improve patient compliance by reducing the number of doses required each day. However, the use of twice a day or once a day administration of Ca2+ antagonists should be not overemphasized in particular situations like those of possible risk of cerebrovascular and/or coronary steal effect primarily in the elderly. The oral formulation of nicardipine investigated with a bioequivalence range > 70% compared to nicardipine immediate release tablets may represent an additional resource for treating elderly patients with concomitant cerebrovascular or coronary heart disease.