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The purpose of this review is to discuss cardiovascular mortality as clinical outcome in the setting of both acute and chronic coronary syndromes (ACS and CCS) with a focus on the clinical evidence supporting the mortality benefit of ticagrelor across multiple subpopulations.Papers considered for this review were retrieved from a PubMed search, using different combinations of keywords (e.g., mortality AND coronary syndrome AND dual antiplatelet therapy AND ticagrelor), without limitations in terms of publication date and language.Prevention of ischemic events and death is of outmost relevance in patients with ACS and CCS, given the high rate of recurrence of such events and fatalities. Owing to the evolving nature of patients with CCS, characterized by a broad spectrum of clinical presentations and previous medical history, as well as the advances in the therapeutic and invasive management of ACS, greater attention to the rate of hard clinical outcomes, improvement in the long-term prognosis, and reduction in the residual risk of recurrent events are increasingly reported among cardiologists. Dual antiplatelet therapy (DAPT) is the cornerstone of antithrombotic therapy aimed at lowering the rate of ischemic events and death in patients treated both conservatively and invasively after ACS, as well as improving prognosis in patients with CCS. Significant differences are emerging among oral P2Y12 inhibitors with regards to mortality benefit.Ticagrelor is an effective and well-tolerated option to attain a meaningful and clinically relevant reduction in cardiovascular mortality in both acute and chronic settings across a broad range of high-risk patient subpopulations with an acceptable payoff in terms of bleeding risk.

Summary This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures. Introduction Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis. Methods We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophagecolony stimulatingfactor (M-CSF), transforming growth factor β (TGFβ), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohisto- chemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines. Results We found an increase of RANKL/OPG ratio, M- CSF, SOST and DKK-1 in fractured patients, whereas TGFβ was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFβ compared to bone, whereas the production of DKK-1 and SOST was higher in bone. Conclusions We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

Negative prognostic factors in amyotrophic lateral sclerosis include advanced age, shorter time from disease onset to diagnosis, bulbar onset and rapid progression rate.To compare progesterone (PROG) and cortisol serum levels in patients and controls and ascertain its relationship to prognostic factors and survival.We assessed serum hormonal levels in 27 patients and 21 controls.Both hormones were 1.4-fold higher in patients. PROG showed a negative correlation with age, positive correlation with survival and positive trend with time to diagnosis. Increased PROG was observed in spinal onset and slow progression patients. No correlation was demonstrated with cortisol.Increased hormonal levels in patients are probably due to hypothalamic-pituitary-adrenal axis activation. Nevertheless, in this preliminary report only PROG correlated positively with factors predicting better prognosis and survival. We hypothesize endogenous PROG and cortisol may be engaged in differential roles, the former possibly involved in a neuroprotective response.

The anesthetic management of a 58 year-old-male suffering from idiopathic pulmonary fibrosis associated with a previous experience of altered dose-response relationship to muscle relaxants is reported. He underwent a gastroendoscopic surgical procedure. After intravenous atropine, remifentanil 3.0 microg kg(-1) was injected over 90 sec. Sixty seconds after the start of remifentanil bolus dose, propofol 2.0 mg kg(-1) was injected and intubation was performed 1 min after the administration of propofol. Anesthesia was maintained by N(2)O, oxygen, sevoflurane (0.5-0.8%) and remifentanil titrated infusion (mean dose of 0.15 mg kg(-1) min(-1)) under spontaneous respiration or assisted ventilation, if the patient was apnoic. The intubating conditions were good, a 30 per cent reduction in MAP was observed after propofol administration. The patient regained consciousness 5 minutes after the end of remifentanil administration and his trachea was extubated without any troubles. Recovery was uneventful without the need of long-term intensive therapy.

To assess the diagnostic accuracy of fetal echocardiography and the outcome of cardiac malformations diagnosed in utero.A retrospective study.The archives of our ultrasound laboratory were searched for fetal cardiac abnormalities in the period 1991-2001.Diagnosis of a fetal cardiac anomaly was made in 339 pregnancies at a mean gestational age of 26.2 weeks. Pathology or a detailed postnatal follow-up was available in 260 cases, and the prenatal diagnosis was accurate in 236 cases (91%). Discrepancies included nine false positive diagnoses (six ventricular septal defects and three coarctation of the aorta) and 15 cases in which a cardiac anomaly different from the one suspected in utero was documented. Of the 142 fetuses with isolated cardiac malformations (no extracardiac anomalies, normal chromosomes) that were delivered in our center, 114 were alive (80.2%) at a mean follow-up of 38 months (range, 1-120 months). In this group of patients, conotruncal anomalies and univentricular lesions were the most frequent types of anomaly, and had a survival rate of 87% and 57%, respectively. Hypoplastic left heart was the most frequent isolated congenital heart defect in infants that were delivered (19 cases) and it was associated with a survival rate of 37%.In expert hands, fetal echocardiography is highly accurate. The long-term prognosis of cardiac lesions diagnosed in utero is similar to that reported in series of infants diagnosed after birth. The only exception is hypoplastic left heart in which the survival rate is much lower than expected from postnatal studies.

Aortico-left ventricular tunnel is a rare congenital communication between the ascending aorta and the left ventricle. Its hemodynamic effect is severe aortic incompetence. Surgery is the only treatment and should be performed before aortic incompetence or ventricular dilation develops. Two neonates with aortico-left ventricular tunnel were operated on at our institution, with closure of the aortic end of the tunnel with a Gore-Tex patch. The 2 patients were discharged in good conditions, and at 112 and 42-month follow-up respectively they are in good health, without medication and with a normal echocardiographic pattern. Aortico-left ventricular tunnel should be treated surgically as soon as possible in order to prevent any damage to the aortic valve and the left ventricle. The operative risk is not low, but results are very encouraging.

A review of large case series, biomechanical studies and the development of surgical approaches and various types of instrumentation have led to different orientations in the surgical treatment of vertebral fractures. The authors present their experience in 67 cases treated by posterior approach using segmental fixation for the instability of the lesion and the possible association of neurologic deficit (Magerl A in 35 cases, B in 25, C in 7; Frankel A in 21 cases, B in 15, C in 9, D in 6). At a mean follow-up of 3 years, treatment by posterior approach allowed us to suitably treat most of the vertebral fractures observed with clinically satisfactory results, but without observing a definite correlation between neurologic recovery and quality of the reduction. The overall realignment of the spine with extension synthesis and adequate geometry and the development of good bone callus allowed us to obtained a stable spine, protecting consolidation of the fractured metamere.

The aim of this study was to verify if surgery is beneficial for patients older than 50 years.Sixty-five patients older than 50 years were operated for a secundum atrial septal defect between November 1974 and November 1998. Preoperative data were obtained from hospital records; postoperative data from written questionnaires or direct telephone interviews. A comparison of pre and postoperative data was possible in 53 patients.The operative mortality was 0%. One patient died of a thromboembolic complication 32 days after surgery. The mean follow-up was 9 +/- 6 years. After surgery, clinical improvement occurred in 22 patients (41.5%) with the majority of them (69.8%) being asymptomatic or only mildly symptomatic. The occurrence of atrial fibrillation/flutter did not decrease after surgery (39.6 vs 26.4%). A thromboembolic event occurred in 2 patients before surgery and in 2 patients postoperatively; all of them had supraventricular arrhythmias and were not taking anticoagulants.Surgical closure of atrial septal defects in patients older than 50 years is feasible. The mortality is low. In this age group, surgery has a beneficial effect on the clinical status of the patients but not on the occurrence of supraventricular arrhythmias that can affect morbidity and mortality in patients who are not treated with anticoagulants.

In this report a new enlarged approach to the anterior cervical spine is presented. A 66-year-old female, having a large C3-C4-C5 chordoma, recurrent after surgery and following radiotherapy, underwent a surgical resection. The approach allows a wide retraction of the nasopharynx, oropharynx and larynx from the midline, only sacrificing the superior laryngeal nerve on one side. Its continuty can be re-established later by adopting the stent in tube technique. The approach we used presents all the risks of infection common in trans-oral approaches. For this reason, closure of the pharynx in two layers must be meticulous and watertight and re-inforced by using a myofascial sternocleidomastoid flap, according to the trachoesophageal fistula closure technique. A correct alignment of the tongue, the pre-plating of the mandible and the correct suture of the vermillion border guarantee excellent cosmetic and functional results.

The increasing attention addressed to the natural medicine is pointed out in this article. The Author emphasizes that in this field nurses play an important role of mediators helping the patient for the transition from the traditional medicine and defines the kind of natural techniques nurse may apply.

Vertebral instability and the neuroaggressiveness produced by the occurrence of cervical metastasis in a neoplastic patient during remission or quiescence of the disease is rare, but it may negatively influence the prognosis of the patient and drastically reduce his or her life expectancy. The authors describe their experience with conservative or surgical treatment in 151 patients affected with cervical metastases.

The authors report 5 cases of giant cell tumor surgically treated. After a mean follow-up of 7 years posterior stabilization alone in the latent form, and wide intralesional curettage in the four aggressive forms allowed for suitable treatment of the lesion, with remission of symptoms leaving stability of the spine intact. Radiation therapy was used successfully in only 1 case of local recurrence occurring 4 months after surgical treatment. Unlike localizations of giant cell tumor in other skeletal segments, whether or not margins are left intact does not seem to influence clinical results.

Repair of an aortico-left ventricular tunnel was successfully accomplished on the second day of life in a neonate with severe cardiac failure. During pregnancy an echocardiographic diagnosis of aortic insufficiency (AI) was made and the type of the malformation was completely clarified after birth. Repair was accomplished using an open patch aortoplasty technique as suggested by Bjork.

Achondroplasia is the most common type of rhizomelic dwarfism. The abnormal spinal development of the achondroplastic dwarf can result in neurologic damage due primarily to the following two syndromes: lumbar spinal canal stenosis and thoracolumbar kyphosis. The authors report the cases observed at their institution, discussing the diagnosis and operative treatment.

Between January 1981 and December 1985 at the Rizzoli Orthopaedic Institute 8 patients affected with atlo-axial instability secondary to os odontoideum were submitted to surgery: all of the patients were characterized by persistent cervical pain and neurological deficit, which was still at an initial stage in 5 cases, and more severe in the remaining 3 (severe spastic tetraparesis). All of the patients were submitted to a similar treatment protocol in three stages: 1) preoperative reduction in halo-plaster, 2) surgical stabilization of C1-C2 by posterior vertebral fusion (limited to C1-C2 in 6 cases and extended as far as the occiput in the remaining 2), 3) postoperative immobilization in halo-plaster for an average of 12 weeks. At follow-up obtained after an average of 4 years and 2 months there was consolidation of the fusion in all of the cases treated: in 1 case, however, revision of the fusion was required 3 and 1/2 months after surgery, whereupon fusion was finally obtained. The total regression of pain was obtained in all 8 of the cases treated and there was evident neurological recovery in the 3 patients who had been characterized by severe spastic tetraparesis prior to surgery. The treatment protocol used in this series of patients proved to be a reliable one. Thus, it was possible to avoid the onset of chronic atlo-axial instability and its severe neurological sequelae in those cases where neurological deficit was still at an initial stage; furthermore, effective recovery was obtained in patients in whom neurological deficit was severe.

Based on their observation of 5 cases of acute posttraumatic cervical disc herniation with medullary lesion, as well as on what is reported in the literature, the authors examine the clinical features of the disease, at the same time evaluating and comparing the major diagnostic studies. What emerges from the study is the importance of NMR and CAT in the diagnosis of the lesion. Finally, the authors emphasize the importance of early surgical treatment.

The authors report three cases in which paraparesis related to a pseudarthrosis occurred several years after a posterior spinal fusion, but with a different mechanism (stretching of the spinal cord for progression of the deformity in kyphosis in two cases, and spinal cord compression for bone overgrowth within the canal in the site of pseudarthrosis in the third patient). Treatment was different. Partial correction of the deformity and stabilization of the spine by combined fusion (anterior and posterior) was sufficient in the first two cases for a complete neurological recovery. Posterior spinal cord decompression and stabilization of the spine by combined fusion was necessary for complete recovery in the third.

The authors report the results obtained in a review of all of the young patients who have been found to be affected with vertebral deformity in an epidemiological study conducted during the academic years 1983-84 and 1984-85. There is predilection for the female sex, which is also more vulnerable to the risk of progression. Menarchal age constitutes the most important period for the progression of the deformity. The most frequent type of curve observed is the double primary one, in particular, right thoracic and left lumbar, which proved to be that most vulnerable to angular progression. The cases which in a previous screening had been defined risk cases were followed-up, and thanks to early diagnosis and suitable treatment surgery was not required in any of these.

New technique of anatomical correction of transposition of the great arteries (TGV) with ventricular septal defect (VSD) and pulmonary stenosis (PS) without using a prosthetic conduit was reported by Lecompte in 1982. We analyse our recent experience with this procedure in three patients and we describe the main advantages and the wide surgical indications with reference to the Rastelli procedure.

Supravalvular aortic stenosis (SAS) is an unusual form of progressive left ventricular outflow tract (LVOT) obstruction, frequently associated with others vascular and physical anomalies. Between July 1980 and July 1986 eight such patients have been operated upon. In seven patients patch aortoplasty (according to McGoon or Doty technique) relieved the stenosis; in one, a two years old boy, with associated severe hypoplasia of the ascending aorta and aortic arch, a left ventricle (LV) - abdominal aorta valved conduit was associated to aortoplasty. One patient died in the operating room with a severe anterior myocardial infarction; seven patients are in good clinical condition at a mean follow-up of 32 months. The aortic supravalvular gradient was dramatically reduced in all patients according with Doppler echocardiography. In our mind, patients with SAS would benefit from an early surgical repair, because of progressive involvement of the aortic valve, coronary arteries and LV. The surgical technique is strictly related to the anatomical situations. Per and postoperative management should rely on the pathophysiology peculiar to this malformation (especially about coronary perfusion). Taking care to these points, the surgical results at a mid term follow-up are now very satisfactory in this cardiac malformation.

Ankylosing spondylitis can produce severe kyphosis in the spine. This is rarer in the cervical spine than in the thoracolumbar region, but it is also more invalidating as it may make it impossible for the patient to look forward as well as causing difficulty in mastication, swallowing and speaking. To correct cervical kyphosis, vertebral osteotomy is performed at the apex of the deformity. The authors present a case of cervical kyphosis due to ankylosing spondylitis successfully treated by the Simmons method.

OBJECTIVES: Primary heart tumours are rare lesions with variegated histological types. We reviewed our 35 years experience with a significant number of primary benign cardiac tumour cases. METHODS: The patient database at University of Bologna was searched to identify patients with primary cardiac tumours between 1974 and 2009. Benign tumours were classified as myxomas and non-myxomas. Ninety-four were myxomas (mean age of 59.1 ± 15.6), and 13 were benign non-myxomas tumours (mean age of 39.7 ± 24.9; P= 0.0001). Complete resection of the masses was performed in all cases except in one. RESULTS: In-hospital mortality was 3% in the myxoma group and 8% in the non-myxoma group. The mean follow-up was 15.1 and 7.4 years for the myxoma and non-myxoma groups, respectively. The long-term survival of discharged patients was 68 ± 7% for the myxoma group and 100% for the non-myxoma group at 20 years, respectively. Recurrence of a tumour occurred only in the myxoma group (four cases) after 1, 3, 5 and 8 years, respectively. Twenty patients had an extracardiac tumour that was diagnosed before operation in 12 (11 in the myxoma group) and during the follow-up in 8 patients (only in the myxoma group). CONCLUSIONS: Primary cardiac tumours can be surgically treated with good short- and long-term results. Mortality and morbidity are mainly due to the status of preoperative patients’. An accurate follow-up is mandatory in order to detect the recurrence of a cardiac tumour such as to exclude the presence or the development of extracardiac tumours that we found frequently associated with the myxoma.

SCO proteins are copper-donor chaperones involved in the assembly of mitochondrial cytochrome c oxidase (COX). Mutations in the two human SCO-encoding genes, SCO1 and SCO2, produce tissue-specific COX deficiencies associated with distinct clinical phenotypes. Here, we report the identification and characterization of scox, the single Drosophila melanogaster SCO-encoding gene. Null mutations of the scox gene are associated with larval lethality, while mutations in its 5'UTR are associated with motor dysfunction and female sterile phenotypes. All mutant phenotypes may be rescued by a transgene encompassing wild-type scox. The analysis of the phenotypes associated with the D. melanogaster scox mutations shows that unimpaired COX assembly and activity is required for biological processes that specifically depend on an adequate energy supply. Finally, we identified the SCO1 orthologs in 39 eukaryotic species informative for a tentative reconstruction of the evolutionary history of the SCO function. Comparison of the exon/intron structure and other key features suggest that eukaryotic SCO genes descend from an intron-rich ancestral gene already present in the last common ancestor of lineages that diverged as early as metazoans and flowering plants.

BACKGROUND AND OBJECTIVE To evaluate the use of remifentanil-propofol administered as target-controlled infusion during awake fibreoptic intubation for anticipated difficult tracheal intubation in acromegalic patients. METHOD In all, 20 consecutive acromegalic patients underwent elective endonasal endoscopic transsphenoidal pituitary surgery. After premedication with midazolam 0.03 mg kg(-1), initially a target-controlled infusion of remifentanil 1.0 ng mL(-1) and propofol 1.5 microg mL(-1) was started. The fibreoptic intubation was performed by the same physician experienced with the fibreoptic technique. During the fibreoptic procedure the target concentrations of remifentanil and propofol ranged between 1.0 and 5.0 ng mL(-1), and between 1.5 and 3.5 microg mL(-1), respectively. Changes in heart rate and mean arterial pressure were recorded during airway manipulation, during tracheal intubation, and at 1 and 3 min after. On the first postoperative day, patient recall and level of discomfort during fibreoptic intubation were evaluated. RESULTS Endotracheal intubation was efficaciously and quickly secured in all patients. A significant increase in mean arterial pressure and heart rate was recorded only during tracheal intubation (P < 0.05). Oxygenation was sufficient and no bradypnea or apnoea was recorded. All patients later described their anaesthetic experience as satisfactory. During fibreoptic intubation, remifentanil (ng mL(-1)) and propofol (microg mL(-1)) mean effect-site concentrations were 3.2 +/- 0.3 and 2.0 +/- 1.0, respectively. CONCLUSION Remifentanil and propofol target-controlled infusion provided satisfactory conscious sedation allowing for successful oral fibreoptic intubation in acromegalic patients with no recall.

Objective We have analyzed, in a clinical multicenter study, the effect of cardiac surgery in adults with congenital heart disease in Italy. Methods We collected clinical data from 856 patients aged 19 years or older who underwent surgical intervention from January 1, 2000, to December 31, 2004. Patients were divided into 3 surgical groups: group 1, palliation (3.1%); group 2, repair (69.7%); and group 3, reoperation (27.4%). Results Preoperatively, 34.6% of patients were in New York Heart Association class I, 48.4% were in class II, 14.2% were in class III, and 2.8% were in class IV. Sinus rhythm was present in 83%. There were 1179 procedures performed in 856 patients (1.37 procedures per patient), with a hospital mortality of 3.1%. Overall mean intensive care unit stay was 2.3 days (range, 1–102 days). Major complications were reported in 247 (28.8%) patients, and postoperative arrhythmias were the most frequent. At a mean follow-up of 22 months (range, 1 month–5.5 years; completeness, 87%), late death occurred in 5 (0.5%) patients. New York Heart Association class was I in 79.3%, II in 17.6%, and III in 2.9%, and only 1 (0.11%) patient was in class IV. Overall survival estimates are 82.6%, 98.9%, and 91.8% at 5 years for groups 1, 2, and 3, respectively. Freedom from adverse events at 5 years is 91% for acyanotic patients versus 63.9% for preoperative cyanotic patients ( P Conclusions Surgical intervention for congenital heart disease in adults is a safe and low-risk treatment. However, patients presenting with preoperative cyanosis show a higher incidence of late adverse events and complications.

Purpose The sensitivity of lymph node excisional biopsy requires validation. Power Doppler ultrasound (US) helps predict the malignant status of lymphadenopathies. We used power Doppler US to select for biopsy the lymph node most suspected of malignancy. Patients and Methods One hundred fifty-two patients having lymphadenopathies with clinical suspicion of lymphoma were divided into two well-matched groups and randomly assigned to undergo either standard or power Doppler US-directed lymph node excisional biopsy. Results Histology showed a malignancy in 64% of patients in the standard group (lymphoma, 49 patients; carcinoma, two patients) and in 87% of patients in the US-assisted group (lymphoma, 62 patients; carcinoma, one patient). There were significantly fewer biopsy-related complications in the assisted group than in the standard group. During the follow-up of the patients with lymph nodes reported as being reactive, 14 of 29 patients in the standard group were rebiopsied and were found to have lymphoma (13 patients) or carcinoma at the subsequent lymph node histology, whereas none of the patients in the assisted group (nine patients) required a second biopsy. Thus, biopsy provided false-negative results for malignancy in 21% of patients affected by lymphoma in the standard group and never in the assisted group (P < .01). Conclusion Power Doppler US is an accurate tool for screening lymphadenopathies to be removed by excisional biopsy in patients with suspected lymphoma.