Formal Synthesis of ent-Cephalotaxine Using a One-Pot Parham-Aldol Sequence.

A short formal synthesis of ent-Cephalotaxine is achieved. The approach features a new Lewis acid-mediated [2,3]-Stevens rearrangement of N-allylated prolineamide to generate a key quaternary stereogenic center. Additionally, a one-pot Parham-aldol sequence was developed to rapidly assemble two of the four rings in the cephalotaxine core.

Iron-Catalyzed Direct C3-Benzylation of Indoles with Benzyl Alcohols through Borrowing Hydrogen.

We present the coupling of primary and secondary benzyl alcohols with indoles to form 3-benzylated indoles and H2O that is catalyzed, for the first time, by a complex of earth-abundant iron. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, sustainability, high functional-group tolerance, and amenability to gram-scale synthesis. On the basis of the preliminary experimental observations, we propose that the reaction proceeds through a borrowing hydrogen process.

ANMCO Position Paper: hospital discharge planning: recommendations and standards.

The hospital discharge is often poorly standardized and affected by discontinuity and fragmentation of care, putting patients at high risk of both post-discharge adverse events and early readmission. The present ANMCO document reviews the modifiable components of the hospital discharge process related to adverse events or re-hospitalizations and suggests the optimal methods for redesigning the whole discharge process. The key principles for proper hospital discharge or transfer of care acknowledge that the hospital discharge: • is not an isolated event, but a process that has to be planned as soon as possible after the admission, ensuring that the patient and the caregiver understand and contribute to the planned decisions, as equal partners; • is facilitated by a comprehensive systemic approach that begins with a multidimensional evaluation process; • must be organized by an operator who is responsible for the coordination of all phases of the hospital patient journey, involving afterward the general practitioner and transferring to them the information and responsibility at discharge; • is the result of an integrated multidisciplinary team approach; • appropriately uses the transitional and intermediate care services; • is carried out in an organized system of care and continuum of services; and • programs the passage of information to after-discharge services.

Science, art, and mistery in the statues and in the anatomical machines of the prince of sansevero: the masterpieces of the "Sansevero Chapel".

During the 18th century in Naples, Raimondo di Sangro, Prince of Sansevero, completed works on the family chapel, the so-called "Cappella Sansevero." The chapel houses statues of extraordinary beauty and spectacularly detailed but also, in the basement, two human skeletons known as the "Anatomical Machines" ("Macchine Anatomiche"). These two skeletons, a man and a pregnant woman, are entirely surrounded by their circulatory systems, just as if these were suddenly fixed. Legend, believed as truth until few years ago, says that Prince Raimondo had prepared and injected an unknown embalming substance in the blood vessels of two of his servants convicting them to eternal fixity. Recent investigations have demonstrated that, while the bones are authentic, the blood vessels are actually extraordinary artifacts that also reproduce some congenital malformations. The dreadful aspect of these two skeletons appears to be in strident contrast with the classic beauty of the statues which glorify and celebrate the ideal of morphology. Conversely, the two Anatomical Machines, protagonists of legends and superstitions since centuries, represent a marvelous example of science mixed with art.

[Cardiovascular prevention in the elderly: limitations and opportunities]. / Prevenzione cardiovascolare negli anziani: limiti e opportunità.

The world's population is ageing; however, the prolonged life expectancy is barely associated with an increase of healthy aging, and an important part of this demographic shift is a rising susceptibility to development and progressive accumulation of multiple chronic illness, challenging healthcare systems. Aging, therefore, represents the major risk factor for multimorbidity, a milestone for progressive loss of resilience and age-related multisystem homeostatic dysregulation. Cardiovascular risk factors, time and comorbidities play a vicious role in the development of heart disease. Among the other comorbidities, age itself is one of the most important risk factors for the development of cardiovascular disease and the prevalence and incidence of cardiovascular disease in the elderly are significantly increased. Elderly subjects, particularly when frail and with comorbidities, however, are scarcely represented in primary and secondary prevention trial aimed to treat hypercholesterolemia, diabetes mellitus and arterial hypertension. In particular, concerns exist about whether treatment should more or less intensive according to tolerability and risk of interactions; as well as there is uncertainty about therapeutic targets at different ages.This article reviews the relationship between ageing and cardiovascular disease, focusing on several issues regarding cardiovascular prevention in the elderly.

Ablating the ventricular insertion of atrio-fascicular mahaim fiber: could be performed safely?

We report a patient who underwent radiofrequency ablation of the distal insertion of an atrio-fascicular accessory pathway with decremental properties because of inability to map a suitable potential alongside the tricuspid annulus. Small, discrete potentials resembling those of Purkinje fiber were found at right ventricular apex. All these potentials showed early activation during tachycardia preceding the QRS onset of various degree. Pace mapping helped to localize the presumed main distal insertion of the atrio-fascicular accessory pathway in a region where damage of the His-purkinje system may ensue. This case report describes catheter ablation of an atriofascicular accessory pathway by targeting its distal (ventricular) insertion site.

Intrahisian conduction disease and junctional ectopic tachycardia.

Junctional ectopic tachycardia (JET) is an uncommon arrhythmia that mainly affects pediatric patients. However, its clinical presentation may rarely occur in adulthood. Owing to its incessant nature, limited responsiveness to antiarrhythmic agents and poor prognosis, catheter ablation of the junctional focus is often required, even though this may be accompanied by the occurrence of complete atrioventricular block. We report the case of a 68-year-old man with episodes of sustained ventricular tachycardia and repetitive JET whose initiation was often anticipated by a sudden intrahisian conduction delay in the immediately preceding sinus beats.

Tissue Doppler and strain imaging: anything left in the echo-lab?

Medline research indicates that an increasing number of manuscripts have been published in the last decade claiming, the feasibility and the potential clinical role of tissue Doppler and strain/strain rate imaging. However, despite this amount of scientific evidence, these technologies are still confined to dedicated, high-tech, research-oriented echocardiography laboratories. In this review we have critically evaluated these techniques, analysing their physical principles, the technical problems related to their current clinical application, and the future perspectives. Finally, this review explores the reasons why these technologies are still defined "new technologies" and the impact of their implementation on the current clinical activity of an echocardiography laboratory.

Evaluation of retinal abnormalities in essential hypertension: qualitative fundoscopy versus central retinal artery resistance index as indicators of target organ damage.

PURPOSE: To compare qualitative fundoscopy with resistance index (RI) of the central retinal artery determined using color Doppler examination as indicators of target organ damage in a large population of patients with essential hypertension. METHOD: We compared qualitative fundoscopy and central retinal artery RI (CRARI) in 459 patients with grade I and II essential hypertension. Correlations with left ventricular mass, carotid structural changes, and diastolic function were investigated. The results were analyzed according to the degree of retinopathy (grade I versus grade II) and CRARI (<0.70 versus >or=0.70). All patients underwent carotid sonography, echocardiography, diastolic function, a sonographic examination of the eye with measurement of CRARI, and examination of the fundus oculi. RESULTS: There was no statistical difference in the parameters studied between patients with grade I and patients with grade II retinopathy on fundoscopy. Patients with CRARI >or=0.70 were older and had higher systolic and pulse pressure, more years of hypertension, increased left ventricular mass index, carotid intima media thickness, and diastolic parameters compared with patients with CRARI <0.70 (p < 0.001). A positive correlation was found between CRARI and age, pulse pressure, carotid intima media thickness, systolic blood pressure, and duration of hypertension, whereas a negative correlation was found between CRARI and diastolic parameters. Age, pulse pressure, carotid intima media thickness, and left ventricular mass index were independently related to CRARI. CONCLUSION: Our findings indicate that CRARI is more reliable than traditional fundoscopy in the evaluation of hypertension-induced organ damage and should be used to measure global cardiovascular risk for tailored therapy.

Retinal breaks observed during pars plana vitrectomy.

PURPOSE: To quantitate the frequency and features of retinal breaks discovered at the time of vitrectomy and to evaluate the outcomes with prophylactic treatment. DESIGN: A consecutive, single-surgeon, retrospective, observational case series from a two-year period. METHODS: Medical records were reviewed for all patients who underwent primary, standard, three-port pars plana vitrectomy (PPV) between January 1, 2000, and December 31, 2001. Intraoperative findings recorded included the number, location, and categorization of retinal breaks and their method of management. Postoperative features recorded included the presence or absence of a retinal detachment (RD). RESULTS: There were 65 retinal breaks found in 48 (11.6%) of 415 eyes and included 30 (7.2%) eyes with definite breaks, nine (2.2%) with suspicious breaks, and nine (2.2%) with probably preexisting breaks. Breaks that were described as being large (n = 5) were more commonly associated with the right-hand sclerotomy (P = .041), although other categories of breaks were not. After surgery, the overall incidence of RD was 2.2% (nine of 415 eyes). The rate of RD among the 48 eyes with retinal breaks (of any category) was also 2.1% (one eye). All RDs in this series occurred more than three months after initial vitrectomy and, accordingly, were probably unrelated to retinal breaks that occurred during surgery. CONCLUSIONS: Recognition of retinal breaks and intraoperative treatment with retinopexy and air-fluid exchange during vitrectomy reduces the postoperative risk of RD to that among eyes without observed intraoperative retinal breaks.

Feasibility, accuracy, and clinical relevance of a rapid thyroid evaluation during carotid duplex ultrasonography in hypertensive patients.

Carotid ultrasonography can detect thyroid nodules without increasing examination duration. The authors analyzed whether management is influenced by reporting such findings during routine carotid ultrasonography in hypertensive patients vs waiting for 6 months to repeat them. This is a population-based study of 1216 hypertensive patients. During carotid ultrasonography, nodule cystic/solid characteristics and size of thyroid changes were recorded. Patients with nodules were divided into those with nodules reported at the moment of diagnosis (group A) and those reported 6 months after diagnosis (group B). The authors monitored patients who underwent thyroid treatment 12 months after carotid ultrasonography. A total of 255 participants had thyroid nodules detected on screening and 99 patients started therapy after discovery. Six months later, as expected, there were more patients undergoing thyroid treatment in the group with nodules reported at time of diagnosis. This difference between groups was not significant, however, 6 months after reporting the nodules, in group B, because the number of patients on therapy significantly increased. Thyroid nodules cannot be ignored during carotid ultrasonography, and reporting their presence is valuable to general practitioners. Thyroid screening during carotid ultrasonography is cost-effective, rapid, sensitive, and specific and may affect the patient's diagnostic and therapeutic management.

Type A acute aortic dissection in nonagenarian: rare but possible.

Acute type A aortic dissection (TA-AAD) is a highly lethal clinical entity that can occur within a wide age range, associated with multiple aetiologies and various clinical presentations. In the very elderly type A aortic dissection frequently presents with non-specific symptoms and signs and is associated with high mortality and morbidity. Thus the clinician must have a high index of clinical suspicion in order to prompt the most appropriate diagnostic-therapeutic strategy. We report a nonagenarian women with TA-AAD, treated successfully with medical therapy.

[Echocardiography and pulmonary arterial hypertension]. / Ecocardiografia ed ipertensione arteriosa polmonare.

Pulmonary Arterial Hypertension (PAH) is an heterogeneous condition brought on by a wide range of causes. It is characterized by structural changes in small pulmonary arteries, that produce a progressive increase in pulmonary artery pressure and pulmonary vascular resistance, ultimately leading to right ventricle failure and death. Given the non-specific nature of its early symptoms and signs, PAH is often diagnosed in its advanced stages. Along with a careful clinical assessment and an accurate electrocardiogram/Chest X-ray interpretation, echocardiography is an essential test in the evaluation of patient with PAH. In fact it not only provides an accurate estimate of pulmonary pressure at rest and during exercise, but may also help to exclude any secondary causes, predict the prognosis, monitor the efficacy of specific therapeutic interventions and detect the preclinical stage of the disease.

Patient selection for transcatheter aortic valve replacement: A combined clinical and multimodality imaging approach.

Transcatheter aortic valve replacement (TAVR) has been validated as a new therapy for patients affected by severe symptomatic aortic stenosis who are not eligible for surgical intervention because of major contraindication or high operative risk. Patient selection for TAVR should be based not only on accurate assessment of aortic stenosis morphology, but also on several clinical and functional data. Multi-Imaging modalities should be preferred for assessing the anatomy and the dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the first line tool in evaluation of this patients giving detailed anatomic description of aortic valve complex and allowing estimating with enough reliability the hemodynamic entity of valvular stenosis. Angiography should be used to assess coronary involvement and plan a revascularization strategy before the implant. Multislice computed tomography play a central role as it can give anatomical details in order to choice the best fitting prosthesis, evaluate the morphology of the access path and detect other relevant comorbidities. Cardiovascular magnetic resonance and positron emission tomography are emergent modality helpful in aortic stenosis evaluation. The aim of this review is to give an overview on TAVR clinical and technical aspects essential for adequate selection.

Transcranial Doppler Ultrasound: Physical Principles and Principal Applications in Neurocritical Care Unit.

Transcranial Doppler (TCD) ultrasonography is a noninvasive ultrasound study, which has been extensively applied on both outpatient and inpatient settings. It involves the use of a low-frequency (≤2 MHz) transducer, placed on the scalp, to insonate the basal cerebral arteries through relatively thin bone windows and to measure the cerebral blood flow velocity and its alteration in many different conditions. In neurointensive care setting, TCD is useful for both adults and children for day-to-day bedside assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, and brain stem death. It also allows to investigate the cerebrovascular autoregulation in setting of carotid disease and syncope. In this review, we will describe physical principles underlying TCD, flow indices most frequently used in clinical practice and critical care applications in Neurocritical Unit care.

[ANMCO Position paper: Hospital discharge planning]. / Position paper ANMCO: Gestione della dimissione ospedaliera.

Hospital discharge is often poorly standardized and is characterized by discontinuity and fragmentation of care, putting patients at high risk of post-discharge adverse events and early readmission. The present ANMCO position paper reviews the modifiable components of the hospital discharge process related to adverse events or rehospitalizations and suggests the optimal methods for redesign the whole discharge process. The key principles for proper hospital discharge or transfer of care acknowledge that hospital discharge:- is not an isolated event, but a process that has to be planned immediately after admission, ensuring that the patient and the caregiver understand and contribute to the planned decisions as equal partners;- is facilitated by a comprehensive systemic approach that begins with a multidimensional evaluation process;- must be organized by an operator who is responsible for the coordination of all phases of the hospital patient pathway, involving afterwards the physician and transferring to them the information and responsibility;- is the result of an integrated multidisciplinary team approach;- uses appropriately the transitional and intermediate care services;- is carried out in an organized system of care and continuum of services;- programs the passage of information to after-discharge services.

[Epidemiology of acute coronary syndrome in Campania]. / Epidemiologia delle sindromi coronariche acute in Campania.

Recent observational studies have pointed out many problems regarding the pre-hospital and in-hospital management of patients with acute coronary syndrome (ACS). The present study analyses the epidemiology of ACS in Campania Region. It has enrolled the 92.3% of coronary care units (CCU) of the Campania. The results indicate that 77% of patients admitted in CCU have ACS and the time of admission in CCU is still too long. Moreover the vast majority of patients arrive at the hospital without emergency ambulance and 48% of patients admitted in CCU for ACS with elevated ST segment do not receive any reperfusion therapy; compared with the 35.1% of patients included in the BLITZ study. The challenge of the SSN in the next future is to improve the "decision making" in the management of patients with ACS. This goal could be reached by an optimal organization of the hospital and out-of-hospital emergency services creating an integrated network of cardiological assistance.

The Coronary Tree of the Anatomical Machines of the Prince of Sansevero: The reality of a legend.

During the 18th century in Naples, Raimondo di Sangro, Prince of Sansevero, gave definitive form to the family chapel, the so-called "Cappella San Severo". The chapel houses not only extraordinarily beautiful and spectacularly detailed statues but also two human skeletons known as anatomical machines ("Macchine Anatomiche") in the basement. These two skeletons, a man and a pregnant woman, are entirely surrounded by their own circulatory system, just as they were suddenly and mysteriously, fixed. Legend, believed as truth until few years ago, tells that Prince Raimondo had prepared and injected an unknown embalming substance in their blood vessels convicting them to eternal fixity. Most recent investigations, however, demonstrated that while the bones are authentic, the blood vessels are actually an extraordinary artifact, even though the perfect reproduction of the coronary vascular tree, including congenital malformations in detail, raises some doubts about the technique used by the Prince. The dreadful aspect of these two skeletons appears to be in strident contrast with the classic beauty of the statues, which glorifies and celebrates the ideal of morphology. Conversely, the two "Anatomical Machines", protagonists of legends and superstitions since centuries, represent a marvelous example of science and art.

Intracardiac echocardiography to guide transseptal catheterization for radiofrequency catheter ablation of left-sided accessory pathways: two case reports.

Intracardiac echocardiography (ICE) is a useful tool for guiding transseptal puncture during electrophysiological mapping and ablation procedures. Left-sided accessory pathways (LSAP) can be ablated by using two different modalities: retrograde approach through the aortic valve and transseptal approach with puncture of the fossa ovalis. We shall report two cases of LSAP where transcatheter radiofrequency ablation (TCRFA) was firstly attempted via transaortic approach with ineffective results. Subsequently, a transseptal approach under ICE guidance has been performed. During atrial septal puncture ICE was able to locate the needle tip position precisely and provided a clear visualization of the "tenting effect" on the fossa ovalis. ICE allowed a better mapping of the mitral ring and a more effective catheter ablation manipulation and tip contact which resulted in a persistent and complete ablation of the accessory pathway with a shorter time of fluoroscopic exposure. ICE-guided transseptal approach might be a promising modality for TCRFA of LSAP.

Left bundle branch block with and without coronary artery disease: which value for a tissue Doppler-derived post-systolic motion?

BACKGROUND: An asynchronous contraction occurring during a prolonged relaxation period, defined as post-systolic motion (PSM), has been described as being a consequence of coronary occlusion but also in other conditions including isolated left bundle branch block (LBBB). The aim of this study was to characterize PSM of the interventricular septum at pulsed tissue Doppler in LBBB with or without stenosis of the left anterior descending coronary artery (LAD). METHODS: Forty-two patients with chronic, complete LBBB and tissue Doppler-derived septal PSM were divided into two groups on the basis of their coronary angiography: 27 without LAD stenosis and 15 with LAD stenosis (> or = 50%). Standard Doppler echocardiography and tissue Doppler of both the middle posterior septum and lateral mitral annulus were performed in the apical 4-chamber view. RESULTS: Standard Doppler diastolic indexes were comparable between the two groups. Septal tissue Doppler showed lower myocardial systolic (Sm) and atrial peak velocities (both p < 0.05), a higher PSM (p < 0.005), and a longer relaxation time (p < 0.02) and pre-contraction time (p < 0.05) in patients with LAD stenosis. A Sm/PSM ratio < 1 was detected in 86% of patients with LAD stenosis and in 22% without LAD stenosis (sensitivity 73%, specificity 77%, positive predictive value 64%, negative predictive value 84%). Tissue Doppler of the mitral annulus showed a significantly longer relaxation time and pre-contraction time and a lower atrial velocity in the presence of LAD stenosis. In the overall population, PSM was positively associated with ejection fraction and negatively with age and septal thickness. In a multiple linear regression analysis, only LAD stenosis (beta = 0.42, p < 0.005) and ejection fraction (beta = 032, p = 0.03) were independent predictors of PSM (cumulative r2 = 0.27, p < 0.002). CONCLUSIONS: Tissue Doppler may be useful to distinguish septal myocardial asynchrony in LBBB with and without LAD stenosis.