Gabriele Ciuti

Combination of D-dimer, F1+2 and residual vein obstruction as predictors of VTE recurrence in patients with first VTE episode after OAT withdrawal

M,Kunapuli SP. Protease-activated receptors 1 and 4 do not stimulate G(i) signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of G(i) signaling. Blood 2002; 99: 3629–36. 10 Tharmapathy P, Fukami MH, Holmsen H. The stimulatory effects of cationic amphiphilic drugs on human platelets treated with thrombin. Biochem Pharmacol 2000; 60: 1267–77. 11 Momo F, Fabris S, Stevanato R. Interaction of fluoxetine with phosphatidylcholine liposomes. Biophys Chem 2005; 118: 15–21.

Comparison of carotid artery blood velocity measurements by vector and standard Doppler approaches.

Although severely affected by the angle dependency, carotid artery peak systolic velocity measurements are widely used for assessment of stenosis. In this study, blood peak systolic velocities in the common and internal carotid arteries of both healthy volunteers and patients with internal carotid artery stenosis were measured by two vector Doppler (VD) methods and compared with measurements obtained with the conventional spectral Doppler approach. Although the two VD techniques were completely different (using the transmission of focused beams and plane waves, respectively), the measurement results indicate that these techniques are nearly equivalent. The peak systolic velocities measured in 22 healthy common carotid arteries by the two VD techniques were very close (according to Bland-Altman analysis, the average difference was 3.2%, with limits of agreement of ± 8.6%). Application of Bland-Altman analysis to comparison of either VD technique with the spectral Doppler method provided a 21%-25% average difference with ± 13%-15% limits of agreement. Analysis of the results obtained from 15 internal carotid arteries led to similar conclusions, indicating significant overestimation of peak systolic velocity with the spectral Doppler method. Inter- and intra-operator repeatability measurements performed in a group of 8 healthy volunteers provided equivalent results for all of the methods (coefficients of variability in the range 2.7%-6.9%), even though the sonographers were not familiar with the VD methods. The results of this study suggest that the introduction of vector Doppler methods in commercial machines may finally be considered mature and capable of overcoming the angle-dependent overestimation typical of the standard spectral Doppler approach.

Cardiac amyloidosis: the heart of the matter

Amyloidosis comprises a unique group of diseases that share in common the extracellular deposition of insoluble fibrillar proteins in organs and tissue including the heart. Cardiac amyloidosis could be primary a part of systemic acquired amyloidosis, or a result of heredofamilial amyloidosis. Although the infiltration of the heart from different types of amyloid results in restrictive cardiomyopathy that manifests with refractory congestive heart failure and conduction abnormalities, unequivocal identification of the deposited amyloidogenic protein is mandatory in order to avoid misdiagnosis and inappropriate treatment. Recent developments in imaging techniques and extracardiac tissue biopsy have minimized the need for invasive endomyocardial biopsy for amyloidosis. Despite advances in treatment, the prognosis of a patient with amyloidosis is still poor and depends upon the underlying disease, and the type and degree of dysfunction of the involved organs. Thus, early diagnosis is mandatory because patients with advanced disease are usually too ill for intensive therapy. This review outlines current approaches to diagnosis, assessment of disease severity, and treatment of cardiac amyloidosis.

Differences between Internal Jugular Vein and Vertebral Vein Flow Examined in Real Time with the Use of Multigate Ultrasound Color Doppler

BACKGROUND AND PURPOSE: The hypothesis that MS could be provoked by a derangement of the blood outflow from the brain has been largely discredited. In part, it was because data on the normal pattern of outflow are scarce and obtained with different methods. The aim of this study was to evaluate the normal pattern of outflow for the vertebral and internal jugular veins in healthy subjects with multigate color Doppler. MATERIALS AND METHODS: Twenty-five volunteers were studied to assess vessel area, mean velocity, and flow for the vertebral and internal jugular veins in the supine and sitting positions. RESULTS: In the sitting position, flow decreases, both in vertebral veins and internal jugular veins, as the total vessel area decreases (from 0.46 ± 0.57 to 0.09 ± 0.08 cm2), even if the mean velocity increases (from 12.58 ± 10.19 to 24.14 ± 17.60 cm/s). Contrary to what happens to the blood inflow, outflow in the supine position, through vertebral and internal jugular veins, is more than twice the outflow in the sitting position (739.80 ± 326.32 versus 278.24 ± 207.94 mL/min). In the sitting position, on application of very low pressure to the skin with the sonography probe, internal jugular veins rarely appear to occlude. A pronounced difference of diameter between internal jugular veins was present in approximately one-third of subjects. CONCLUSIONS: Our results support the view that other outflow pathways, like the vertebral plexus, play a major role in the normal physiology of brain circulation and must be assessed to obtain a complete picture of blood outflow.

Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis

Objective To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage. Methods Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP). Results At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4±9.5 vs 2.6±3.8, p<0.001). Among patients with abnormal RFR, 13 (68.4%) showed a CCr reduction of ≥2 ml/min/year, with a final CCr of ≤70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up. Conclusions Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.

The thrombophilic pattern of different clinical manifestations of venous thromboembolism: a survey of 443 cases of venous thromboembolism.

Although pulmonary embolism (PE) and deep vein thrombosis (DVT) share many risk factors, it is uncertain whether thrombophilic abnormalities may impact differently on the development of these two clinical manifestations of venous thromboembolism (VTE). To give further insight into this issue, we estimated the association of PE with different types of thrombophilia and evaluated whether these abnormalities have a different prevalence in patients presenting with PE, alone or associated with DVT, as compared with those with isolated DVT. In this study 443 consecutive patients with a first episode of VTE and 304 matched healthy controls underwent laboratory screening for thrombophilia, including natural anticoagulants, factor V Leiden and prothrombin G20210A polymorphisms, antiphospholipid antibodies, homocysteine, factor VIII, and lipoprotein(a). Of the 443 patients, 224 patients had isolated DVT, 144 had combined DVT/PE, and 75 had isolated PE. At least one thrombophilic abnormality was detected in 72.8% of DVT, 66% of DVT/EP, and 60% of isolated PE patients. A high prevalence of hyperhomocysteinemia and elevated lipoprotein(a) levels was found in all patients with no significant differences among the three groups. The prevalence of prothrombin G20210A polymorphism and of elevated factor VIII levels was significantly higher in patients with DVT and DVT/PE than in controls, but not in those with isolated PE, whereas factor V Leiden polymorphism was associated with isolated DVT but not with DVT/PE or isolated PE. In conclusion, the thrombophilic burden seems different in isolated PE versus DVT with or without PE, suggesting that PE may encompass a different pathophysiological process of thrombosis to DVT.

Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an Internal Medicine setting.

INTRODUCTION Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department. MATERIALS AND METHODS Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12weeks. RESULTS One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p=0.014, p=0.009 and p=0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p=0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients. CONCLUSIONS We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.

Multigate Quality Doppler Profiles Technology in Vascular, Obstetrics and Cardiology Applications

Multigate Quality Doppler Profiles (QDP) is a Fast Fourier Transform (FFT) based Doppler technology recently integrated within a commercial ultrasound scanner. QDP represents a novel analysis tool, which is able to simultaneously detect and show the velocity components, present in the blood flow of multiple vessels, without any frame rate reduction. QDP can be used in conjunction with the DIR algorithm to enhance the visibility of the flow direction information. The present work describes the use of QDP in Cardiology (Pediatric and Adult), Vascular (cervical venous and arterial system) and Obstetrics (uterine arteries). In vivo and in vitro tests are reported, showing the QDP behavior with respect to insonation angle changes and its advantages with respect to classic Doppler technologies. The QDP is demonstrated to be a precise positioning tool for the Pulsed Wave Doppler (PW) sample volume (SV) and a qualitative direct real time indicator of blood flow variations. It is also shown ideal for the study of turbulent flow, for minor reflux detection and for easier sampling of the blood flow signal within the examined vessel (or vessels) in case of movements.

Biohumoral markers as predictor of right ventricular dysfunction in AL Amyloidosis

Abstract Aim: In AL amyloidosis, the importance of right ventricle (RV) involvement has recently been underlined and its role in predicting prognosis has been emphasized. Little is known about the relationship between RV involvement, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin levels. Aim of our study was to clarify the relationship between NT-proBNP and troponin and RV involvement and analyze their independent value as predictors of RV dysfunction. Methods and Results: We examined 76 consecutive patients with biopsy-proven AL amyloidosis. Each patient received complete clinical evaluation, troponin I, NT-proBNP assay and comprehensive echocardiographic evaluation. Considering a tricuspidal annulus plane systolic excursion (TAPSE) value <16 mm, 23 patients (30%) presented RV systolic dysfunction, whereas 53 (70%) did not. Patient with reduced TAPSE had thicker left ventricle (LV) walls and RV free walls, reduced LV fractional shortening, impaired LV diastolic function and worse LV and RV myocardial performance index. For RV dysfunction the best predictive value for NT-proBNP was identified as 2977 ng/l with sensitivity and specificity of 87% and 84%, respectively; best cut-off for troponin I was identified as 0.085 ng/l, with sensitivity and specificity of 85% and 90% respectively. At multivariable logistic regression analysis, both NT-proBNP and troponin I emerged as independent predictors of RV dysfunction presence but troponin appears to have a higher predictive power. Conclusion: Our study demonstrated that cut-off values of 2977 ng/ml for NT-proBNP and 0.085 ng/l for troponin were able to identify a subgroup of AL patients with RV dysfunction. Troponin I is more accurate and seems to be the best biohumoral marker of RV dysfunction.

Hypokalemia-induced rhabdomyolysis.

We read with great interest the review article by Bagley et al. [1] on pathophysiology, diagnosis, complications and treatment options for rhabdomyolysis. Rhabdomyolysis is a syndrome characterized by acute damage of the skeletal muscle with necrosis of muscle fibers, leading to the release of potentially toxic muscle cell breakdown products (creatinine phosphokinase—CPK—and myoglobin) into the circulation, which may result in potential life-threatening complications, such as acute myoglobinuric renal failure [2]. As reported by the authors, rhabdomyolysis can be caused by various conditions such as traumatic, inflammatory, and metabolic muscle diseases, intense exercise, drugs (i.e., statins) and toxins, infections, malignant hyperthermia, and neuroleptic malignant syndrome. Among rare causes the review also quoted electrolytic abnormalities, in particular diuretic-induced hypokalemia [3, 4]. We recently experienced a case of diuretic-induced acute hypokalemic rhabdomyolysis in a 63-year-old man who was admitted to our hospital for the onset of myalgia and muscle weakness of all limbs. He had hypertension treated with angiotensin-converting enzyme inhibitors, b-blockers and antialdosteronic agents. Three weeks prior, antihypertensive therapy had been modified with the addition of indapamide and withdrawal of canrenone. At physical examination, severe girdle weakness and reduced deep tendon reflexes without any loss of sensation were observed. Severe hypokalemia (1.9 mEq/L), high levels of creatinine phosphokinase (11,917 U/L), high transaminases (aspartate transaminase 208 and alanine transaminase 99 U/L, respectively), aldolase (93.5 U/L) and serum and urinary myoglobin levels (3,295 and 14,074 ng/mL, respectively) were detected. The electrocardiogram was characterized by sinus rhythm with diffuse ST depression, T wave inversion, a prominent U wave, and QT-interval prolongation. Electromyography revealed a myopathic pattern with involvement of proximal muscles. Indapamide was withdrawn, and treatment with intravenous potassium and potassium canrenoate was started. Serum potassium, CPK and myoglobin levels gradually returned to normal without development of renal insufficiency. Improvement of laboratory tests was accompanied by recovery of muscle strength with normalization of electrocardiographic and electromyographic findings. Suspecting a primary hyperaldosteronism, an abdomen computed tomography was performed, revealing a mass in both adrenal glands. The diagnosis was then confirmed by the detection of low plasma renin concentration with a twofold increase of plasma aldosterone concentration. Rhabdomyolysis is usually diagnosed by elevation in serum CPK, and many clinicians use five times the upper limit of normal (about 1,000 U/l) as cut-off level. Myoglobinuria can aid but is not necessary for the diagnosis because myoglobin can be quickly cleared from the body in well-hydrated patients with normal renal function. Serum levels of aldolase, lactate dehydrogenase and transaminases may also be elevated, although not specific to rhabdomyolysis. Clinical manifestations include muscle pain, weakness, dark urine, fever, tachycardia, nausea and vomiting. E. Grifoni (&) A. Fabbri G. Ciuti A. Moggi Pignone SOD Medicina Interna ad Orientamento all’Alta Complessità Assistenziale 3, AOU Careggi, Largo Brambilla 3, 50134 Florence, Italy e-mail: grifonielisa@gmail.com