Serum and cerebrospinal fluid neurofilament light chains measured by SIMOA™, Ella™, and Lumipulse™ in multiple sclerosis naïve patients.

BACKGROUND: Neurofilament light chains (NfL) are cytoskeletal biomarkers of axonal damage, about 40-fold higher in cerebrospinal fluid (CSF) compared to serum, and requiring ultrasensitive techniques to be measured in this latter fluid. OBJECTIVES: To compare CSF and serum NfL levels in multiple sclerosis (MS) patients using different platforms. METHODS: 60 newly diagnosed relapsing-remitting MS patients (38 females; median age: 36.5 years, range: 15-60) were enrolled before steroid or disease-modifying treatments. CSF and serum NfL were measured with: the commercial Ella™ microfluidic platform (Bio-Techne), the Lumipulse™ Chemiluminescent Enzyme ImmunoAssay (Fujirebio), and the SIMOA™ on the SR-X instrument using NF-light assays (Quanterix). RESULTS: CSF and serum NfL absolute levels strongly correlated between assays, although being more elevated with Ella™. Passing-Bablok regression showed high agreement in measuring CSF NfL between assays (with greater proportional difference using Ella™), and very high agreement for serum comparing SIMOA™ and Lumipulse™. Similarly, the Bland-Altman comparison evidenced lower biases for Lumipulse™ for both fluids. CONCLUSIONS: CSF and serum NfL in naïve MS patients are reliably measured with all assays. Although not interchangeable, SIMOA™ and Lumipulse™ showed high agreement for serum and CSF values.

Multicenter study on hepatitis C virus infection in patients with dilated cardiomyopathy. North Italy Transplant Program (NITP).

Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

Multicenter study of stentless valve replacement in the small aortic root.

OBJECTIVE: A clinical study was conducted to evaluate the results of stentless porcine valves in patients with a small aortic root (19- and 21-mm aortic anulus). METHODS: Of 567 patients, from 4 surgical institutions, 171 patients (30.1%) had a small aortic root, comprising 163 cases with calcified aortic stenosis and 8 cases with predominant valvular insufficiency. Sixty patients had associated mitral or coronary lesions. Mean age was 72 +/- 4.2 years. Forty-seven patients with a small aortic root had a 19-mm anulus, and 124 patients had a 21-mm anulus. The body surface area was, respectively, 1.55 +/- 0.2 m2 and 1.78 +/- 0.45 m2. Hemodynamic evaluation of the stentless valve comprised serial measures of mean gradients, effective orifice area, and left ventricular mass reduction. Complication rates for secondary events were evaluated over a 6-year period. RESULTS: The hospital mortality rate was 3.5%. The mean gradients after the first year were 9 +/- 2 mm Hg and 6 +/- 1.7 mm Hg in patients with a 19-mm and a 21-mm anulus, respectively. Effective orifice area was 1.45 +/- 0.3 cm2 and 1.72 +/- 0.4 cm2. Gradients and surfaces remained stable throughout the study period. Aortic regurgitation was zero to trace. Left ventricular mass at discharge and at 1 year were, respectively, 296 +/- 127 g and 215 +/- 102 g for patients with a 19-mm anulus and 281 +/- 75 g and 236 +/- 15 g for patients with a 21-mm anulus. CONCLUSIONS: Stentless valves are a suitable device for elderly patients with small aortic roots, which leave only mild residual obstruction.

[The Tirone Davis operation in a young patient with Marfan syndrome. Description of a clinical case]. / Intervento di Tirone David in giovane paziente affetta da sindrome di Marfan. Descrizione di un caso clinico.

We report a case of a young woman affected with Marfan's syndrome, with an ascending aortic aneurysm and mild aortic insufficiency, who underwent a valve-sparing operation as described by Tirone David. In many patients with Marfan's syndrome, aortic valve dysfunction is caused by dilatation of the sinotubular junction with distortion of the sinuses of Valsalva, and often with intact aortic valve leaflets. In these patients, if the aortic valve leaflets are normal at echocardiography, a more aggressive approach may be advisable in order to prevent irreversible damage to the aortic valve leaflets. We believe that surgery is indicated when the aortic root increases rapidly, even if it does not reach a diameter of 50 mm, which represents the current indication for asymptomatic patients with ascending aortic aneurysm. This makes it possible to perform a valve-sparing operation instead of the composite replacement of the aortic valve and ascending aorta, which is still considered the standard treatment for these patients. The procedure described here represents an attractive choice for managing aortic root dilatation and annuloaortic ectasia in Marfan patients, with the benefit of avoiding all the well-known complications involved in prosthetic aortic valves.

[The recurrence of a postinfarct interventricular defect. An alternative approach]. / Recidiva di difetto interventricolare postinfartuale. Un approccio alternativo.

Despite improvement of surgical techniques and perioperative management, the postinfarction ventricular septal defect still remains a surgical challenge associated with a significant early and late mortality. Furthermore, the recurrence of the defect after primary correction occurs in about 10-25% of patients and the operative risk increases because of difficult dissection that is often complicated by previous patent grafts. Repair of recurrent posterior postinfarction ventricular septal defect has generally been performed by ventriculotomy in the infarcted zone. This approach carries a significant mortality and morbidity from hemorrhage or further compromise of ventricular function. We propose an alternative approach to a recurrent defect that, when the rupture is posterior, makes it possible to achieve its complete visualization, avoiding any further ventriculotomy in an already impaired ventricle. This transatrial approach seems to be a safe technique. Moreover, the simplicity of this operation and the patient's rapid recovery contrasts remarkably with the transventricular approach used in previous patients. Nevertheless, care must be taken to avoid damage to the tricuspid valve.

Non-small cell lung cancer. Morphology and DNA flow cytometry.

OBJECTIVE: To correlate stage-related and histologic features of non-small cell lung cancer (NSCLC) with DNA flow cytometric parameters. STUDY DESIGN: The clinicopathologic features, DNA flow cytometric parameters (ploidy type, S-phase fraction and DNA index [DI]) of 72 surgically resected NSCLC were reviewed. RESULTS: NSCLC were classified on the basis of their DI in diploid, peridiploid, hypotriploid, triploid, hypertriploid, tetraploid, hypertetraploid and multiploid tumors. DI was significantly related to pleural infiltration, pT, histologic type and evidence of necrosis. Tumors infiltrating the pleura were mostly triploid or hypertriploid; high pT stages were also hypertetraploid. Adenocarcinomas showed a wide DI distribution, squamous carcinomas were mostly diploid, triploid or hypertriploid and large cell carcinomas were mostly triploid, hypertriploid and hypertetraploid. The best combination of features able to predict disease relapse was pT plus pN plus grading and divergent differentiation. CONCLUSION: Many stage-related and histologic features are associated with particular DI classes, which vary in relation to the feature itself and, in some cases, regardless of classical methods of grading and histologic typing. DNA content analysis highlights greater biologic heterogeneity in NSCLC than evidenced morphologically.

[Transesophageal and epicardial echocardiography in the evaluation of conservative surgery of the mitral valve. Complementary methods?]. / L'ecocardiografia transesofagea ed epicardica nella valutazione della chirurgia conservativa della valvola mitrale. Metodiche complementari?

BACKGROUND: Over the last two decades several new surgical methods for repairing a regurgitant mitral valve have been proposed. Unfortunately, early applications of such techniques were not always encouraging because the evaluation in the operating room led to false optimism due to a marked difference between static and functional anatomy of the repaired valve. By means of intraoperative echocardiography, be it transesophageal or epicardial, it is now possible to assess the functional result immediately after valvuloplasty and to decide about further surgery, right at the operating table. MATERIALS AND METHODS: Thirty-six patients (mean age 61.8 years) who underwent mitral valve repair were studied; all underwent preoperative transthoracic echocardiography in the week preceding surgery, and intraoperative transesophageal echo before cardiopulmonary bypass. The surgical results were evaluated by epicardial and/or transesophageal echocardiography in the operating room, and by transthoracic and/or transesophageal approach during follow-up. RESULTS: In 5 patients with intraoperative echocardiography done before valve repair, leaflets pathology and subvalvular apparatus were better evaluated. Besides, in 3 patients the more evident calcification of the leaflets led the surgeon to decide on direct replacement rather the reconstruction of the valve. The postoperative assessment has shown an unsatisfactory correction in 8 patients (24%). In 4 of these patients an important mitral regurgitation was reported and in 2 there was a moderate regurgitation. In the last 2, a iatrogenic stenosis had resulted. Of these 8 patients, 6 underwent valve replacement using an artificial valve. The other 2 patients (one with moderate stenosis and the other with moderate regurgitation) did not undergo a second operation because of the excessive operating time taken for valvuloplasty and the advanced age of the patients. During follow-up, from 6 to 54 months, a remarkable mitral regurgitation was present in 4 patients, one being severe and the other moderate. A persistence of ventricular dilatation was present only in these patients, while in the remainder the left ventricular diameters were normal. Finally, the mitral valve area after six months was between 1.5 an d4 cm2. CONCLUSIONS: Intraoperative echocardiography, both transesophageal and epicardial, can help the surgeon by giving him useful diagnostic information, if carried out before reconstructing the mitral valve with regurgitation. Its application is even more useful if applied straight after the surgical intervention. Unsatisfactory results may be evidenced at once and the operating team will decide right at the table for further repair or replacement, thus avoiding a second operation and the relevant risks.

[The usefulness of transesophageal echocardiography in the follow-up of patients operated on for replacement of the ascending aorta with a tubular-valvular prosthesis (Cabrol's intervention)]. / Utilità dell'ecocardiografia transesofagea nel follow-up dei pazienti operati di sostituzione dell'aorta ascendente con protesi tubulo-valvolata (intervento di Cabrol).

OBJECTIVES: The usefulness of transesophageal echocardiography (TEE) in assessing the postoperative results of aortic root replacement (Cabrol's procedure) was evaluated. METHODS: Between 1986 and 1993, 31 patients underwent replacement of the aortic valve and ascending aorta by a composite graft using the Cabrol procedure. Twenty-six patients had annuloaortic ectasia, two type I DeBakey dissection and four type II dissection. Hospital mortality was 9.7%. Studies were performed in 18 patients, two to 70 months (mean 27.5 months) after composite graft replacement. The following features were examined: prosthetic aortic valve function, coronary graft morphology and function, tubular graft and aneurysm wrapped around morphology and dimensions, presence of intimal flap, false lumen and thrombus in the false lumen and persistence of right atrial fistula. RESULTS: Periprosthetic leakage with significant regurgitation was detected by TEE in 3 (16.6%) of 18 patients. In one patient with infected aortic graft a fistula between the periprosthetic space and the right ventricle was detected (confirmed at reoperation). In another patient occlusion of the graft for left coronary artery was noted. In three patients (16.6%) an aneurysm of the periprosthetic space with perivalvular leakage and persistence of the fistula with the right atrium was visualized. In the two patients operated for DeBakey type I dissection an intimal flap persisted distal to the graft and in one patient flow was detected in the false lumen, while it was totally obliterated in the other. CONCLUSIONS: 1) Complications after Cabrol's procedure are not infrequent; although the real importance of some of them (periprosthetic aneurysm, persistence of dissection) is uncertain, a careful follow-up may be essential to improve the long term survival. 2) TEE is a useful and well-tolerated procedure for postoperative follow-up of patients who underwent aortic root replacement with Cabrol's procedure.

The cellular basis of dilated cardiomyopathy in humans.

The present investigation was designed to evaluate whether end-stage cardiac failure in patients affected by dilated cardiomyopathy (DC) was dependent upon extensive myocyte cell death with reduction in muscle mass or was the consequence of collagen accumulation in the myocardium independently from myocyte cell loss. In addition, the mechanisms of ventricular dilation were analysed in order to determine whether the changes in cardiac anatomy were important variables in the development of intractable congestive heart failure. DC is characterized by chamber dilation, myocardial scarring and myocyte hypertrophy in the absence of significant coronary atherosclerosis. However, the relative contribution of each of these factors to the remodeling of the ventricle is currently unknown. Moreover, no information is available concerning the potential etiology of collagen deposition in the myocardium and the changes in number and size of ventricular myocytes with this disease. Morphometric methodologies were applied to the analysis of 10 DC hearts obtained from patients undergoing cardiac transplantation. An identical number of control hearts was collected from individuals who died from causes other than cardiovascular diseases. DC produced a 2.2-fold and 4.2-fold increase in left ventricular weight and chamber volume resulting in a 48% reduction in mass-to-volume ratio. In the right ventricle, tissue weight and chamber size were both nearly doubled. Left ventricular dilation was the result of a 59% lengthening of myocytes and a 20% increase in the transverse circumference due to slippage of myocytes within the wall. Myocardial scarring represented by segmental, replacement and interstitial fibrosis occupied approximately 20% of each ventricle, and was indicative of extensive myocyte cell loss. However, myocyte number was not reduced and average cell volume increased 2-fold in both ventricles. In conclusion, reactive growth processes in myocytes and architectural rearrangement of the muscle compartment of the myocardium appear to be the major determinants of ventricular remodeling and the occurrence of cardiac failure in DC.

Structural basis of end-stage failure in ischemic cardiomyopathy in humans.

BACKGROUND: Ischemic cardiomyopathy is characterized by myocyte loss, reactive cellular hypertrophy, and ventricular scarring. However, the relative contribution of these tissue and cellular processes to late failure remains to be determined. METHODS AND RESULTS: Ten hearts were obtained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identical number of control hearts were collected at autopsy from patients who died from causes other than cardiovascular disease, and morphometric methodologies were applied to the analysis of the left and right ventricular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed increases of 85%, 47%, and 103%, respectively. Corresponding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricles, was responsible for the difference in the assessment of myocyte hypertrophy at the ventricular, tissue, and cellular levels. Left ventricular muscle cell hypertrophy was accomplished through a 16% and 51% increase in myocyte diameter and length, whereas right ventricular myocyte hypertrophy was the consequence of a 13% and 67% increase in these linear dimensions, respectively. Moreover, a 36% reduction in the number of myocytes included in the thickness of the left ventricular wall was found. Collagen accumulation in the form of segmental, replacement, and interstitial fibrosis comprised an average 28% and 13% of the left and right ventricular myocardia, respectively. The combination of cell loss and myocardial fibrosis, myocyte lengthening, and mural slippage of cells resulted in 4.6-fold expansion of left ventricular cavitary volume and a 56% reduction in the ventricular mass-to-chamber volume ratio. CONCLUSIONS: These results are consistent with the contention that both myocyte and collagen compartments participate in the development of decompensated eccentric ventricular hypertrophy in the cardiomyopathic heart of ischemic origin.

[Cardiac pacing during open heart surgery (author's transl)]. / L'elettrostimolazione nella chirurgia a cuore aperto.

Cardiac pacing by means of temporary wires inserted during open heart surgery is an established useful adjunct to post-operative care. Optimal rate can be imposed to the heart with transiently depressed function, arrhythmias can be suppressed by overdriving and atrioventricular synchronization sometimes can be reestablished, with a resulting improvement of cardiac output. We routinely insert wires on the right ventricle, and on the right atrium wherever excitable. Wires have been inserted in 383 consecutive patients, significantly contributing to the control of bradiarrhythmias, the suppression of PVCs, and the improvement of low cardiac output states.