Global longitudinal strain for prediction of mortality in ST-segment elevation myocardial infarction and aortic stenosis patients: two sides of the same coin.

OBJECTIVE: Global longitudinal strain (GLS) predicts major adverse events in ST-segment elevation myocardial infarction (STEMI) and aortic stenosis (AS). Different cut-off values and different end-points have been proposed for prognostic stratification. We aimed to verify whether a single GLS cut-off value can be used to identify increased risk of all-cause death in STEMI and AS. PATIENTS AND METHODS: One-hundred- seventeen successfully treated first STEMI (age 63.8±12.5 yrs, 70% men) and 64 AS (age 80.3±6.9 yrs, 44% men) patients, undergoing echocardiography before discharge and before AS treatment, respectively, were retrospectively analyzed. GLS was analyzed, together with pulmonary artery systolic pressure (PASP), Killip class and Genereux stage. End-point was all-cause death at 6-month follow-up. RESULTS: All-cause death occurred in 4 (3.4%) STEMI and 5 (7.8%) AS patients (p=ns). AS patients who died had GLS similar to died STEMI patients (9.7±2.1 vs. 11.3±1.7, p=ns). GLS cut-off ≤12% predicted death with 89% sensitivity and 70% specificity (AUC 0.84, p=0.001): STEMI and AS patients with GLS ≤12% had worse survival than STEMI and AS patients with GLS >12% (log-rank p=0.001). At multivariate Cox regression analysis, lower GLS values independently predicted death (HR 0.667, 95% CI 0.451-0.986, p=0.042), and the prediction model was improved when GLS was added to old age, significant comorbidities, PASP and Killip/Genereux stage (χ2 6.691 vs. 1.364, p=0.010). CONCLUSIONS: Died patients with STEMI and AS show similar values of GLS. A unique cut-off value of GLS can reliably be used to stratify the risk of all-cause death at 6-month follow-up in both two clinical settings.

NO, CO and H2 S: What about gasotransmitters in fish and amphibian heart?

The gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen sulphide (H2 S), long considered only toxicant, are produced in vivo during the catabolism of common biological molecules and are crucial for a large variety of physiological processes. Mounting evidence is emerging that in poikilotherm vertebrates, as in mammals, they modulate the basal performance of the heart and the response to stress challenges. In this review, we will focus on teleost fish and amphibians to highlight the evolutionary importance in vertebrates of the cardiac control elicited by NO, CO and H2 S, and the conservation of the intracellular cascades they activate. Although many gaps are still present due to discontinuous information, we will use examples obtained by studies from our and other laboratories to illustrate the complexity of the mechanisms that, by involving gasotransmitters, allow beat-to-beat, short-, medium- and long-term cardiac homoeostasis. By presenting the latest data, we will also provide a framework in which the peculiar morpho-functional arrangement of the teleost and amphibian heart can be considered as a reference tool to decipher cardiac regulatory networks which are difficult to explore using more conventional vertebrates, such as mammals.

The Chromogranin A-derived sympathomimetic serpinin depresses myocardial performance in teleost and amphibian hearts.

Chromogranin A (CgA) is an acidic protein co-stored with catecholamines, hormones and neuropeptides in the secretory granules of endocrine, neuronal and other cell types (including cardiomyocytes). Proteolytic cleavage in the C terminus of CgA generates a 2.9kDa peptide named serpinin (Serp; Ala26Leu) that can be modified at its N terminus to form a pyroglutamate residue (pGlu-Serp). In the rat heart, both peptides increase contractility and relaxation through a ß-adrenergic-like action mechanism. Accordingly, Serp and pGlu-Serp were proposed as novel myocardial sympatho-adrenergic modulators in mammals. On a comparative basis, here we report the actions of Serp and pGlu-Serp on myocardial contractility in three poikilotherm vertebrate species: the eel (Anguilla anguilla), the goldfish (Carassius auratus) and the frog (Rana esculenta). Using isolated working heart preparations, we show that pGlu-Serp reduces stroke volume in all species tested, while Serp reduces contractility in the frog heart, but is uneffective in eel and goldfish hearts. In the goldfish and frog hearts, pGlu-Serp activates the Nitric Oxide/cGMP pathway involving Endothelin-1 B receptors (frog) and ß3 adrenergic receptors (goldfish). pGlu-Serp-treated hearts from goldfish and frog show increased cGMP content. Moreover, the exposure of the frog heart to pGlu-Serp is accompanied by an increased expression of activated eNOS and Akt. In conclusion, this first report showing that pGlu-Serp inhibits mechanical cardiac performance in teleost and amphibians supports an evolutionary role of the CgA system, and particularly its serpinin component, in the sympatho-adrenergic control of the vertebrate heart.

Nesfatin-1 as a new positive inotrope in the goldfish (Carassius auratus) heart.

The hypothalamic neuropeptide Nesfatin-1 is present in both mammals and teleosts in which it elicits anorexigenic effects. In mammals, Nesfatin-1 acts on the heart by inducing negative inotropism and lusitropism, and cardioprotection against ischemic damages. We evaluated whether in teleosts, Nesfatin-1 also influences cardiac performance. In the goldfish (Carassius auratus), mature, fully processed Nesfatin-1 was detected in brain, gills, intestine and skeletal muscle, but not in the cardiac ventricle. However, on the isolated and perfused working goldfish heart, exogenous Nesfatin-1 induced a positive inotropic effect, revealed by a dose-dependent increase of stroke volume (SV) and stroke work (SW). Positive inotropism was abolished by inhibition of adenylate cyclase (AC; MDL123330A) and cAMP-dependent kinase (PKA; KT5720), suggesting a cAMP/PKA-mediated pathway. This was confirmed by the increased cAMP concentrations revealed by ELISA on Nesfatin-1-treated hearts. Perfusion with Diltiazem, Thapsigargin and PD98059 showed the involvement of L-type calcium channels, SERCA2a pumps and ERK1/2, respectively. The role of ERK1/2 and phospholamban in Nesfatin-1-induced cardiostimulation was supported by Western blotting analysis. In conclusion, this is the first report showing that in teleosts, Nesfatin-1 potentiates mechanical cardiac performance, strongly supporting the evolutionary importance of the peptide in the control of the cardiac function of vertebrates.

Synthesis of a heterogeneous artificial metallolipase with chimeric catalytic activity.

A solid-phase strategy using lipase as a biomolecular scaffold to produce a large amount of Cu(2+)-metalloenzyme is proposed here. The application of this protocol on different 3D cavities of the enzyme allows creating a heterogeneous artificial metallolipase showing chimeric catalytic activity. The artificial catalyst was assessed in Diels-Alder cycloaddition reactions and cascade reactions showing excellent catalytic properties.

PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients.

BACKGROUND: Agents targeting programmed death-1 receptor (PD-1) and its ligand (PD-L1) are showing promising results in non-small-cell lung cancer (NSCLC). It is unknown whether PD-1/PD-L1 are differently expressed in oncogene-addicted NSCLC. METHODS: We analysed a cohort of 125 NSCLC patients, including 56 EGFR mutated, 29 KRAS mutated, 10 ALK translocated and 30 EGFR/KRAS/ALK wild type. PD-L1 and PD-1 expression were assessed by immunohistochemistry. All cases with moderate or strong staining (2+/3+) in >5% of tumour cells were considered as positive. RESULTS: PD-1 positive (+) was significantly associated with current smoking status (P=0.02) and with the presence of KRAS mutations (P=0.006), whereas PD-L1+ was significantly associated to adenocarcinoma histology (P=0.005) and with presence of EGFR mutations (P=0.001). In patients treated with EGFR tyrosine kinase inhibitors (N=95), sensitivity to gefitinib or erlotinib was higher in PD-L1+ vs PD-L1 negative in terms of the response rate (RR: P=0.01) time to progression (TTP: P<0.0001) and survival (OS: P=0.09), with no difference in PD1+ vs PD-1 negative. In the subset of 54 EGFR mutated patients, TTP was significantly longer in PD-L1+ than in PD-L1 negative (P=0.01). CONCLUSIONS: PD-1 and PD-L1 are differentially expressed in oncogene-addicted NSCLC supporting further investigation of specific checkpoint inhibitors in combination with targeted therapies.

Surgical treatment of redundancy after retrosternal esophagocoloplasty.

Redundancy is a well-recognized complication of esophageal replacement with colonic interposition, occurring several years after surgery. In a small number of patients, symptoms are disabling and might require reoperation. This article describes the surgical treatment of a 54-year-old male presenting with severe dysphagia, malnutrition and recurrent aspiration pneumonia, progressively developed 30 years after esophageal replacement with retrosternal ileocolonic interposition for caustic strictures.

Glomus tumour of the lung: case report and literature review.

Glomus tumours are uncommon neoplasms usually arising in the dermis and subcutaneous tissues where glomus bodies are generally found. Occasionally glomus tumours can occur in extracutaneous sites such as the gastrointestinal tract, bone, genitourinary system and respiratory tract. Primary pulmonary glomus tumours are very rare (only 17 cases reported in the literature), and are often confused with other solid neoplasms such as carcinoids, hemangiopericytomas and tumours belonging to the family of Ewing's sarcoma/primitive neuroectodermal tumours. We present a case of a primary pulmonary glomus tumour originating in the right main bronchus with focal invasion of the submucosa in a 69-year-old man. Histological and immunohistochemical features are reported. The current literature is briefly reviewed, with special attention to differential diagnosis and malignancy criteria.

Use and efficacy of abciximab in an unselected population with acute myocardial infarction treated with primary angioplasty: data from AMI-Florence registry.

AIMS: We sought to evaluate the determinants and the potential benefit of abciximab use in unselected patients with acute myocardial infarction treated with primary angioplasty. METHODS AND RESULTS: Based on the AMI-Florence registry, we analyzed 461 consecutive acute myocardial infarction patients treated with primary angioplasty, 280 (61%) of whom received abciximab. For each patient, a propensity score indicating the likelihood of abciximab treatment was calculated. Compared to those not treated, patients treated with abciximab were at lower risk. At multivariate analysis, the direct admission to a hospital with angioplasty facilities significantly increased the probability of receiving abciximab (OR 1.99, 95% CI 1.30-3.03, p=.001), while older age (OR 0.97, 95% CI 0.95-0.98, p<.0001), non-anterior location (OR 0.58, 95% CI 0.38-0.88, p=.011) and Killip class >1 (OR 0.53, 95% CI 0.32-0.87, p=.013), were negative predictors of abciximab use. Primary angioplasty had a higher success rate in patients treated with abciximab (99.3% versus 96.5%, p=.03). In-hospital and 1-year mortality were significantly lower in patients treated with abciximab (2.5% versus 13.3%, p<.0001, and 7% versus 21%, p<.0001, respectively). At multivariate analysis patients treated with abciximab had a significantly lower risk of in-hospital mortality (OR 0.35, 95% CI 0.14-0.93, p=.035), and a marginally lower risk of death at 1-year follow-up (HR 0.58, 95% CI 0.32-1.03, p=.065). These results did not change when the propensity score was included into the analyses. CONCLUSIONS: In the real practice, abciximab is more frequently used in patients at lower risk, particularly when directly admitted to a hospital with angioplasty facilities. Abciximab use is associated with a significant reduction in early mortality. A trend toward a reduced mortality is maintained also at 1 year.

Neurocysticercosis: surgical treatment of an autochthonous case in a non-endemic region.

OBJECTIVE AND IMPORTANCE: This study describes a case of autochthonous neurocysticercosis in a non endemic region where a differential diagnosis with more frequent single parenchymal lesions must be carried out. CLINICAL PRESENTATION: The patient presenting generalized seizures and coma status under the suspicion of cerebral neoplasia was admitted to the neurosurgery division. MRI showed the presence of an ovoidal cystic lesion in right-frontotemporal region. INTERVENTION: After right fronto-temporal osteoplastic bone flap elevation and usual dural tacking and opening, trans-scissural subaracnoid access was made possible by microsurgical strumentation in right Sylvian fissure. A cystic, translucid lesion was identified in the deep Sylvian fissure, involving the distal segment of the fissure and the frontal lobe, the cystic lesion was removed surgically. Pathological examination showed a typical picture of neurocysticercosis. CONCLUSIONS: After both surgical and chemotherapeutic treatment with albendazole the outcome was successful. The diagnosis of neurocysticercosis should be taken into account in the presence of generalized seizures possibly due to single parenchymal lesions, even in non-endemic regions for this parasitic infection.

Lung transplantation for cystic fibrosis.

BACKGROUND: Lung transplantation is a robust therapeutic option to treat patients with cystic fibrosis. PATIENTS AND METHODS: Since 1996, 109 patients with cystic fibrosis were accepted onto our waiting list with 58 bilateral sequential lung transplants performed in 56 patients and two patients retransplanted for obliterative bronchiolitis syndrome. RESULTS: Preoperative mean FEV(1) was 0.64 L/s, mean PaO(2) with supplemental oxygen was 56 mm Hg, and the mean 6-minute walking test was 320 m. Transplantation was performed through a "clam shell incision" in the first 29 patients and via bilateral anterolateral thoracotomies without sternal division in the remaining patients. Cardiopulmonary bypass was required in 14 patients. In 21 patients the donor lungs had to be trimmed by wedge resections with mechanical staplers and bovine pericardium buttressing to fit the recipient chest size. Eleven patients were extubated in the operating room immediately after the procedure. Hospital mortality of 13.8% was related to infection (n = 5), primary graft failure (n = 2), and myocardial infarction (n = 1). Acute rejection episodes occurred 1.6 times per patient/year; lower respiratory tract infections occurred 1.4 times per patient in the first year after transplantation. The mean FEV(1) increased to 82% at 1 year after operation. The 5-year survival rate was 61%. A cyclosporine-based immunosuppressive regimen was initially employed in all patients; 24 were subsequently switched to tacrolimus because of central nervous system toxicity, cyclosporine-related myopathy, or renal failure, obliterative bronchiolitis syndrome, gingival hyperplasia, or hypertrichosis. Ten patients were subsequently switched to sirolimus. Freedom from bronchiolitis obliterans at 5 years was 60%. CONCLUSIONS: Our results confirm that bilateral sequential lung transplantation is a robust therapeutic option for patients with cystic fibrosis.

[Different effects of subacute administration of S. Croce oligo-mineral water on colonic vs rectal constipation]. / Effetti differenziati sulla stipsi colica rispetto a quella rettale del trattamento subacuto con acqua oligominerale S. Croce Sponga.

OBJECTIVE: To evaluate the effect of a subacute administration of oligomineral water "S. Croce Sponga" in subjects affected by chronic constipation. PATIENTS AND METHODS: Hospitalized patients (13 females and 4 males) have been classified according to radiologically evaluated transit times if affected by colonic or rectal constipation, and by clinical interview if suffering from chronic colonic constipation due to increased resistance or hypomotility. Treatment consisted in the administration of 1.5 litres/day of S. Croce Sponga oligomineral water for 7 days or a control water of known composition. The study started after seven days of hospital stay. RESULTS: The results of the study showed that S. Croce Sponga oligomineral water was effective in resolving the condition of chronic colonic constipation in almost 80% of the subjects. No effect was observed in subjects with chronic rectal constipation. CONCLUSIONS: Treatment with S. Croce Sponga oligomineral water resolved chronic colonic constipation by enhancing velocity of the colonic transit.

The effect of injection speed on the pain of lidocaine infiltration.

OBJECTIVE: To determine whether reducing the speed of injection is effective in reducing injection pain for buffered and unbuffered lidocaine solutions. METHODS: A prospective, single-blind, randomized, crossover, laboratory study was performed. Adult volunteers were recruited from ED staff at an urban teaching hospital to serve as subjects. Twenty-nine subjects each received 4 1-mL injections into the dorsum of the hands. Each subject received fast and slow injections of buffered and unbuffered lidocaine. Subjects rated the pain of each injection on a 100-mm visual analog scale (VAS). Mean pain scores for each intervention were compared using analysis of variance. RESULTS: The mean pain VAS score for fast injection of buffered lidocaine was 14.1 mm. For slow buffered injection, the mean pain score was 11.4 mm (p = 0.98). For unbuffered lidocaine, the means were 28.7 mm for fast injection and 22.2 mm for slow injection (p = 0.40). CONCLUSIONS: Reducing injection speed did not produce a statistically significant change in injection pain for either buffered or unbuffered solutions.

Evaluation of mitral stenosis by cine magnetic resonance imaging.

To evaluate the ability of cine magnetic resonance imaging (cine MRI) in the assessment of mitral stenosis (MS), we studied 20 patients (14 women and 6 men, mean age 60.6 +/- 8.5 years) with rheumatic mitral valve stenosis by using an 0.5 T magnet. Cine MRI showed several signs of MS. Mitral leaflet thickening, reduced diastolic opening, and abnormal valve motion toward the left ventricular outflow tract were all common features. MS was also characterized by an abnormal diastolic transmitral signal from blood. Both left atrial and left ventricular dimensions were similar to those obtained at two-dimensional echocardiography (2-DE) (r = 0.89 and r = 0.86, respectively; p less than 0.001). A significant relationship was also found between the maximum mitral leaflet separation measured by cine MRI in diastole and the mitral valve area as calculated using the pressure half-time method and continuous wave Doppler (r = 0.81; p less than 0.001). These data indicate the improved ability of MRI to detect and assess MS and also suggest that this technique may contribute to the noninvasive assessment of MS.