Intra-procedural monitoring protocol using routine transthoracic echocardiography with backup trans-oesophageal probe in transcatheter aortic valve replacement: a single centre experience.

AIM: The aim of this study is to describe our 9-year experience in transcatheter aortic valve replacement (TAVR) using transthoracic echocardiography (TTE) as a routine intra-procedural imaging modality with trans-oesophageal echocardiography (TEE) as a backup. METHODS AND RESULTS: From January 2008 to December 2017, 1218 patients underwent transfemoral TAVR at our Institution. Except the first 20 cases, all procedures have been performed under conscious sedation, with fluoroscopic guidance and TTE imaging monitoring. Once the TTE resulted suboptimal for final result assessment or a complication was either suspected or identified on TTE, TEE evaluation was promptly performed under general anaesthesia. Only 24 (1.9%) cases required a switch to TEE: 6 cases for suboptimal TTE prosthetic valve leak (PVL) quantification; 12 cases for haemodynamic instability; 2 cases for pericardial effusion without haemodynamic instability; 4 cases for urgent TAVR. The 30-days and 1-year all-cause mortality were 2.1% and 10.2%, respectively. Cardiac mortality at 30-days and 1-year follow-up were 0.6% and 4.1%, respectively. Intra-procedural and pre-discharge TT evaluation showed good agreement for PVL quantification (k agreement: 0.827, P = 0.005). CONCLUSION: TTE monitoring seems a reasonable imaging tool for TAVR intra-procedural monitoring without delay in diagnosis of complications and a reliable paravalvular leak assessment. However, TEE is undoubtedly essential in identifying the exact mechanism in most of the complications.

Effects of chronic elevation of atrial natriuretic peptide and free fatty acid levels in the induction of type 2 diabetes mellitus and insulin resistance in patients with mitral valve disease.

BACKGROUND AND AIMS: The relationship between atrial natriuretic peptide (ANP), increased free fatty acid (FFA) and insulin resistance in patients with mitral valve disease (MVD), a group characterised by elevated atrial pressure and increased ANP levels, is not defined. The present study was performed to evaluate, in MVD patients, the relationship between increased ANP and FFA levels and insulin resistance and the role of mitral valve replacement/repair in ameliorating these metabolic alterations. Conversely, coronary heart disease (CHD) patients were evaluated before and after coronary artery bypass grafting (CABG), since they are known to be insulin resistant in the presence of chronic FFA increase. METHODS AND RESULTS: Fifty MVD patients and 55 CHD patients were studied before and 2 months after surgery and compared with 166 normal subjects. Before surgery, 56% of MVD patients had impaired glucose tolerance or newly diagnosed type 2 diabetes after a standard oral glucose load and this percentage decreased to 46% after surgery. In CHD, impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetic patients were 67% of patients before and after CABG. In MVD, left atrial (LA) volume, ANP, FFA incremental area and insulin levels were higher and Insulin Sensitivity (IS) index significantly reduced while after surgery, LA volume, ANP and FFA significantly decreased and IS index significantly improved. In CHD, insulin resistance and hyperinsulinaemia were present both before and after surgery with increased tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels. CONCLUSION: In MVD, a higher degree of abnormal glucose tolerance and insulin resistance are associated to increased levels of ANP and FFA, while these metabolic alterations are improved by mitral valve replacement/repair surgery. Clinical Trial.gov registration number NCT 00520962.

[Acute renal failure after videolaparoscopic surgery: an avoidable complication?]. / L'insufficianza renale acuta postchirurgia laparoscopica: evitabile complicanza?

Videolaparoscopic surgery exposes the abdominal organs to the mechanical effect of pneumoperitoneum at pressure values between 12 and 15 mm Hg, which are considered safe. Nevertheless, experimental data have shown that this pressure range can represent a hemodynamic risk factor as it may induce a decrease in the venous return to the right ventricle, a decrease in cardiac output, and activation of the sympathetic nervous system and renin angiotensin system. We report two cases of acute renal failure that occurred soon after videolaparoscopy in young female patients without any evidence of ongoing renal disease. Patient A was 29 years old and was submitted to videolaparoscopic surgery in a follow-up program after surgical treatment of ovarian cancer; patient B was 15 years old and was submitted to the surgical removal of a monolateral ovarian cyst. In neither of the cases was it necessary to perform hemodialysis. Patient A underwent a renal biopsy under ultrasound guidance; optic microscopy showed only in ra- and extraglomerular capillary congestion. In both cases the acute renal failure resolved completely and the patients where discharged with normal renal function. Taking in to account that normal renal venous pressure levels are around 4 mmHg we think that a) a 15 mmHg pneumoperitoneum may represent a risk factor during videolaparoscopic surgery mainly if the patient's extracellular volume is not properly expanded; b) administration of nonsteroidal anti-inflammatory drugs in order to prevent surgical pain may inhibit vasodilatory prostaglandin availability; c) onset of oliguria during the surgical procedure suggests that extracellular volume expansion is required.

[Treatment of arterial hypertension in diabetic nephropathy. Certainties and hypotheses]. / Le traitement de l'hypertension artérielle dans la néphropathie diabétique. Certitudes et hypothèses.

Clinical observation has long emphasized the importance of arterial hypertension in the course of diabetic nephropathy and recent studies suggest that hypertension might play a decisive pathogenetic role in the course of the disease, hence the necessity of correcting the hypertension of diabetic patients has by now been universally accepted. There is, however, still some uncertainty concerning the usefulness of acting preventively on so-called microhypertension; in other words, whether early antihypertensive drug treatment can prevent diabetic nephropathy. This paper discusses the criteria to be followed in the choice of antihypertensive medication during diabetic nephropathy giving special attention to pathophysiological considerations. Moreover, it also discusses the effects of antihypertensive drugs currently regarded as first-choice agents, i.e. calcium antagonists and the angiotensin converting enzyme inhibitors, on intrarenal hemodynamics.

Minimal change nephrotic syndrome with cecum adenocarcinoma.

Membranous glomerulonephritis is the most common glomerular disease associated with malignancy, the association of minimal change glomerulopathy with solid tumor is still uncommon. We report a 72-year-old man with nephrotic syndrome due to minimal change glomerular disease; an accurate seek of underlying malignancy revealed a cecum adenocarcinoma. We had a complete remission of nephrotic syndrome after surgery of carcinoma.

The PTH-calcium relationship curve in secondary hyperparathyroidism, an index of sensitivity and suppressibility of parathyroid glands.

A sigmoidal relationship, fitting a four-parameter model, has been demonstrated in in vivo and in vitro studies to link the parathyroid hormone (PTH) secretion rate and calcium concentration changes. In uraemic patients different patterns of calcium-mediated PTH secretion were reported in different types of renal bone diseases and a shift to the right and a steeper slope has been observed in secondary hyperparathyroidism. To gain more information that could predict indexes for successful medical therapy we investigated the calcium-PTH sigmoidal relationship in 42 hyperparathyroid patients with different degrees of secondary hyperparathyroidism; we classified as moderate those patients presenting basal PTH (PTHbas) < 600 pg/ml and bone alkaline phosphatase (AP) < 500 U/l, and severe those with a PTHbas > or = 600 pg/ml and bone AP > or = 500 U/l. Changes in ionized calcium (iCa) were induced by calcium-free dialysis on the first day, to induce hypocalcaemia up to serum iCa 3.5 mEq/l, and calcium 8 mEq/l dialysis on the third day, to induce hypercalcaemia. The moderate hyperparathyroidism patients had PTHmax, PTHmin and slope, calculated in absolute values and relative values, lower than severe hyperparathyroidism patients but they did not differ in the minimal to maximal PTH ratio. In the moderate group the PTHbas correlated with all the curve parameters except PTHmin, calculated both in absolute and percentage values, while in the severe group PTHmin was the only parameter correlating to the PTHbas. In conclusion, by performing the dynamic test, we found that some glands were not suppressible among moderate hyperparathyroidism patients.

Thrombospondin and transforming growth factor-beta 1 increase expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in human MDA-MB-231 breast cancer cells.

BACKGROUND: Thrombospondin is a high molecular weight adhesive glycoprotein that has been shown to function in mechanisms of tumor progression. The authors' previous studies have shown that thrombospondin promotes human lung carcinoma invasion by up-regulation of the plasminogen activator system through a mechanism involving the activation of transforming growth factor-beta 1 (TGF-beta 1). In this study, a similar thrombospondin-mediated mechanism operative in breast carcinoma cells is described. METHODS: The effect of thrombospondin and TGF-beta 1 on the capacity of a line of breast carcinoma cells to activate plasminogen was measured as well as the physiologic consequences of these activities on cell adhesion and proliferation. Plasminogen activation was assessed by measuring the plasmin activity and plasminogen activator inhibitor-1 (PAI-1) levels in cell-conditioned media and the cell-associated urokinase-type plasminogen activator (uPA) levels. RESULTS: Treatment of MDA-MB-231 breast carcinoma cells with either thrombospondin or TGF-beta 1 caused increased secretion of PAI-1 with a concomitant decrease in plasmin activity, whereas cell-associated uPA expression was increased with respect to controls. Thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) stimulated the cells to secrete 5.5- and 6.7-fold more PAI-1 than controls, respectively, and caused decreased plasmin activity in the cell culture medium. Conversely, either thrombospondin (40 micrograms/ml) or TGF-beta 1 (5 ng/ml) caused the cells to express 4.55- and 5.38-fold more uPA than controls, respectively. Thrombospondin and TGF-beta 1 induced a more flattened and spread appearance in the cells with no effect on proliferation. These effects could be reversed with antibodies to either thrombospondin or TGF-beta 1 and were not due to contamination of thrombospondin with active TGF-beta 1. CONCLUSIONS: Thrombospondin and TGF-beta 1 function similarly to increase cell-associated uPA and cell-secreted PAI-1. These data suggest that thrombospondin may not only function as an adhesive molecule, but through a mechanism involving the activation of TGF-beta 1, may modulate cell surface protease expression. In addition, these observations suggest that thrombospondin and TGF-beta 1 could promote metastasis by increasing uPA-mediated cell invasion, whereas through the action of PAI-1, also protect blood-born tumor emboli from destruction by host fibrinolytic enzymes.

Chemical parathyroidectomy for recurrence of secondary hyperparathyroidism.

To avoid the risks of reoperation, we treated 15 uremic patients on regular extracorporeal dialysis and affected by hyperparathyroidism recurring after subtotal parathyroidectomy with ultrasound-guided ethanol injection. Follow-up was extended to 12 months after the last injection and for 11 patients to 24 months. Plasma parathyroid hormone concentration, as measured with a carboxyterminal parathyroid hormone (c-PTH) radioimmunoassay (normal, 0.2 to 2 ng/mL), significantly decreased from a basal value of 19.29 +/- 14.73 ng/mL to 11.19 +/- 9.54 ng/mL at 1 month, 7.45 +/- 4.99 ng/mL at 6 months, 6.91 +/- 4.71 ng/mL at 12 months, and 6.51 +/- 3.89 ng/mL at 24 months. Total and bone alkaline phosphatase decreased in parallel. The only remarkable side effect was transient dysphonia, which occurred in two cases. These data suggest that the technique of ultrasound-guided fine-needle ethanol injection might be a valuable alternative to surgery for recurrent hyperparathyroidism after subtotal parathyroidectomy in selected patients. This should be confirmed in larger series of patients and with a more prolonged follow-up.

Thrombospondin (TSP) and transforming growth factor beta 1 (TGF-beta) promote human A549 lung carcinoma cell plasminogen activator inhibitor type 1 (PAI-1) production and stimulate tumor cell attachment in vitro.

A growing body of evidence has recently implicated TSP and TGF-beta in the process of malignancy, such as tumor cell proliferation, tumor angiogenesis, and metastasis. The purpose of the present study was to evaluate potential mechanisms of TSP and TGF-beta in tumor cell attachment and invasion. Our results indicate that both TSP and TGF-beta promoted tumor cell attachment and spreading in the presence of plasminogen. The mechanism for these effects appeared to be due, in part, to the capacity of TSP and TGF-beta to induce tumor cell production of (PAI-1). PAI-1, which is a natural inhibitor of tumor-cell associated urokinase-type plasminogen activator (uPA) activity, inhibited activation of plasminogen to plasmin in the growth media, thereby preventing plasmin-induced detachment of cells. The TSP-promoted production of PAI-1 could be inhibited not only by anti-TSP antibodies but also by a neutralizing antibody against TGF-beta. These results suggest that TSP by a mechanism involving TGF-beta can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor-associated production of PAI-1.

Rest and exercise hemodynamics of stentless porcine bioprostheses in aortic position.

Mechanical and conventional stented bioprostheses, because of need for anticoagulants, hemodynamic characteristics and long-term durability, do not represent the optimal heart valve replacement device. In this study we compared the hemodynamic function of a stented aortic bioprosthesis (St Jude Bioimplant), implanted in 10 patients, with a stentless porcine aortic bioprosthesis (Biocor) implanted in 7 patients, by means of Doppler echocardiography early postoperative at rest (T1) and 6 months later at rest (T2a) and during exercise (T2b). Mean and peak systolic gradients across stentless porcine prostheses were significantly lower than across stented bioprostheses (T1 p = 0.008 and p = 0.004; T2a p < 0.0001 and p < 0.0001; T2b p < 0.0001 and p < 0.0001, respectively). Our results show that systolic and diastolic mechanical stress on biological components of a glutaraldehyde-fixed stentless porcine aortic bioprosthesis is much lesser than on stented bioprostheses. This feature has appeared evident at rest and much more after exercise testing. The reduction of systolic and diastolic stress is expected to determine lower calcification degree and longer durability of stentless porcine aortic bioprostheses. Moreover, aortic valve replacement by means of stentless bioprostheses allows the implantation of a 1 size (2 mm) larger device, appearing favourable especially in small aortic annulus. On the basis of these promising results we suggest that stentless bioprostheses are a valid alternative to stented bioprostheses for aortic valve replacement. However, patient population is too small and the follow-up is too short to draw a definite statement about long-term hemodynamic performance of this device.

Myocardial revascularization with bilateral internal thoracic artery in patients with left main disease: an incremental risk?

Although the long-term patency of the internal thoracic artery (ITA) has been well proved, there is still some concern about its preoperative performance. We considered 80 patients with left main disease (mean age 60.2 years) who underwent coronary artery bypass grafting in our institute from March 1988 to September 1992. Patients with left main disease were divided into 2 groups: group I-38 patients receiving only ITA grafts on the left coronary system and group II-42 patients having a single ITA graft together with saphenous vein grafts on the left coronary system. No patients in group I received a saphenous graft on the left coronary system and three patients with right coronary artery involvement received total arterial myocardial revascularization with the use of the inferior epigastric artery. Perioperative complications in group I and group II patients were, respectively: myocardial necrosis in 2 (6.9%) and 3 (8.8%), use of intraaortic balloon pump in 2 (6.9%) and 2 (5.9%). No death occurred in either group. In our experience, the use of bilateral ITA grafts in patients with left main stenosis was not related to an incremental risk. We conclude that left main disease should not be considered as counterindication to the extensive use of arterial conduits.

[The treatment of arterial hypertension in diabetes mellitus. Choices and problems]. / Trattamento dell'ipertensione arteriosa in corso di diabete mellito. Scelte e problemi.

Recent studies indicate that arterial hypertension in diabetes mellitus is a paramount pathogenetic step in the evolution and acceleration of diabetic macro- and microangiopathy and in particular in the development of nephropathy and uremia. This paper deals with the clinical problems of antihypertensive treatment in diabetic patients and discusses the antihypertensive repertory with the aim at determining the best drug choice in the individual case. In the light of our present pathophysiologic knowledges of the intrarenal effects of the various classes of antihypertensive drugs the possibility of preventing diabetic nephropathy is discussed.

Morphological alterations of neurons and astrocytes in guinea pigs exposed to low levels of inorganic lead.

Both astrocytes and neurons potentially undergo structural and functional alterations in the brains of animals exposed to low levels of lead (Pb). No morphometric studies of astrocytes have been reported to date in animals in low Pb exposure. In the present study, morphometric measurements of astrocytes and pyramidal neurons in the frontoparietal cortex were made in guinea pigs exposed postnatally (5 or 10 days) or prenatally (gestational day 22 to birth) to low Pb levels. Although few significant effects of Pb treatment were detected by the rigorous statistical model applied, a recurring trend was noted for postnatal Pb treatment to increase astrocyte maximum diameter (dmax). In addition, prenatal Pb treatment was associated with increased apical and basal dendritic length, increased total apical dendrites per cell and an increased basal branching complexity in neurons.

[Diabetic nephropathy and arterial hypertension: the physiopathological aspects and antihypertensive treatment]. / Nefropatia diabetica ed ipertensione arteriosa: aspetti fisiopatologici e trattamento antiipertensivo.

The purpose of our review is to delineate the pathogenic steps linking arterial hypertension in diabetes to diabetic nephropathy. The results of recent studies suggest that arterial hypertension in diabetes might lay a decisive pathogenetic role in the evolution of diabetic nephropathy: the existence of a higher ratio of erythrocytic Na/Li counter-transport in nephropathic diabetics as well as higher pressure values in the parents of diabetics who develop nephropathy indicates that hypertension may be casually related to renal complications. Diabetes-associated hypertension involves the modification of two important pressure- regulation factors: 1. an alteration in extracellular volume and increased renal absorption of sodium which leads to an expanded pool; 2. increased cardiovascular reactivity to norepinephrine and angiotensin II, an effect which might be related to increased intracellular calcium. Hyperfiltration seems to be present at the onset of diabetes, and arterial hypertension increases the transglomerular pressure gradient which is thought to play an important role in the pathogenesis of kidney damage. Antihypertensive drugs such as ACE-inhibitors and calcium channel blockers tend to protect the regulation of renal function. This could be explained by the fact that ACE-inhibitors suppress the trophic effects of angiotensin II on the nephron, while calcium channel blockers might interfere with intracellular processes involved in cell hypertrophy that require the interaction of calcium ions. In the management of diabetes prevention of diabetic nephropathy requires early and careful correction of diabetes-associated hypertension. We discuss the major groups of antihypertensive drugs, their metabolic side-effects and intrarenal induced hemodynamic changes.

Ultrasound-guided percutaneous fine-needle ethanol injection into parathyroid glands in secondary hyperparathyroidism.

To reduce parathyroid hormone concentrations in uraemic patients refractory or hyporesponsive to calcium supplements and active metabolites of vitamin D, we developed in 1982 a new parathyroid ablative technique consisting of percutaneous fine-needle ethanol injection (PFNEI) into enlarged parathyroid glands under ultrasonic guidance. Fifty uraemic patients have been treated. Decreases in carboxy terminal parathyroid hormone (PTH) were 50% or more in 13 of 50 patients followed up (26%) at 1 month, in 13 of 48 (27%) at 6 months, and in 9 of 25 (36%) at 12 months. Decreases of 30% or more in PTH were obtained in 21 of 50 (42%), in 25 of 48 (52%), and in 15 of 25 (60%). In 'responsive' patients, serum total alkaline phosphatase was significantly reduced [from 579 +/- 645 U/l to 360 +/- 354 U/l (P less than 0.01) at 6 months, and to 273 +/- 311 U/l (P less than 0.01) at 12 months] and bone isoenzyme decreased similarly [from 482 +/- 608 U/l to 256 +/- 344 U/l (P less than 0.005), and to 225 +/- 354 U/l (P less than 0.01)]. The best results were in seven patients who had relapsed after subtotal parathyroidectomy. Declines in PTH of 30% or more were observed in four of seven patients at 1 month, in six of the seven (85%) at 6 months, and in all four patients seen after 12 months. The treatment corrected hypercalcaemia, making it possible to start or to increase daily vitamin D treatment. Side-effects were mild, rare, and transient.

Bone mineral and aluminum concentrations in patients undergoing CAPD.

CAPD results in continuous peritoneal transfer of hormones and minerals involved in the pathogenesis of renal osteodystrophy (RO). Moreover, although CAPD patients seem to have better control of serum phosphate concentration than hemodialysis patients, the need for aluminum-containing phosphate binders (ACPB) may still be present. In a prospective study meant to investigate the evolution of RO, we obtained 79 bone biopsies in 29 uremic patients (20 male, 9 female; age 25-59, mean 46). Of these, 22 were obtained at the beginning of treatment, 24 after 24 months, 23 after 36 months and 10 after 60 months. All patients were treated with CAPD (Viaflex, Baxter 2-2.5 L x 4-5 bags/day; Ca(++) + 3.5, Mg(++) 1.5 mEq/L) as the first modality of therapy and received oral calcitriol, aluminum hydroxyde and/or calcium carbonate and magnesium hydroxyde in order to maintain serum calcium (Ca) and phosphorus within the normal range. Qualitative bone histology, bone Ca and magnesium (Mg) (Flame atomic absorption spectroscopy) and aluminum (Al) concentration (Graphite furnace atomic absorption spectrometry) were determined. CAPD achieves a good control of RO as indicated by the tendency toward a decreased incidence of mixed osteodystrophy and predominant hyperparathyroid bone disease and improvement of osteoid lesions. A defective Ca content of bone is persistent in the observed period and positively correlated to bone Mg concentration. An increased level of Al was shown in the serum and bone. The highest bone Al content was found among patients with predominant osteoid bone disease. Also in CAPD, patients consuming ACPB are at risk of bone Al accumulation despite the low Al levels in the dialysate.