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Aims The Heart Failure Association of the European Society of Cardiology (HFA-ESC) proposed a definition of advanced heart failure (HF) that has not been validated, yet. We assessed its prognostic impact in a consecutive series of patients with high-risk HF. Methods and results The HELP-HF registry enrolled consecutive patients with HF and at least one high-risk 'I NEED HELP' marker, evaluated at four Italian centres between 1(st) January 2020 and 30(th) November 2021. Patients meeting the HFA-ESC advanced HF definition were compared to patients not meeting this definition. The primary endpoint was the composite of all-cause mortality or first HF hospitalization. Out of 4753 patients with HF screened, 1149 (24.3%) patients with at least one high-risk 'I NEED HELP' marker were included (mean age 75.1 +/- 11.5 years, 67.3% male, median left ventricular ejection fraction [LVEF] 35% [interquartile range 25%-50%]). Among them, 193 (16.8%) patients met the HFA-ESC advanced HF definition. As compared to others, these patients were younger, had lower LVEF, higher natriuretic peptides and a worse clinical profile. The 1-year rate of the primary endpoint was 69.3% in patients with advanced HF according to the HFA-ESC definition versus 41.8% in the others (hazard ratio [HR] 2.23, 95% confidence interval [CI] 1.82-2.74, p < 0.001). The prognostic impact of the HFA-ESC advanced HF definition was confirmed after multivariable adjustment for relevant covariates (adjusted HR 1.98, 95% CI 1.57-2.50, p < 0.001). Conclusions The HFA-ESC advanced HF definition had a strong prognostic impact in a contemporary, real-world, multicentre high-risk cohort of patients with HF.

Background: Pleural adhesions are frequently encountered in patients undergoing reduction pneumoplasty. We evaluated the impact that: pleural adhesions had on the surgical technique and outcome of thoracoscopic reduction sty. Methods: 59 operated patients were divided into 2 groups depending on the presence(group A) or absence (group B) of pleural adhesions. Results: At inter-group comparison (A versus B) a significant difference was found for mean duration of operation (128+/-55 min versus 73+/-33 min; p

Three cases of peritoneal cystic mesothelioma are reported. All patients were women who had undergone previous abdominal surgery for unrelated conditions. Tumors consisted of solitary and multiple cystic masses involving the abdominal and pelvic peritoneum. The cysts focally infiltrated the muscularis externa of the small intestine in case 1, the outer muscular layer of the uterus in case 2, and the omental tissue in case 3. These findings give morphologic support to the borderline clinical behavior of this tumor that often recurs and support the hypothesis that previous surgery may play a role in its pathogenesis.

The occurrence of occult thyroid carcinoma at autopsy was examined in 507 consecutive autopsies performed over one-year in subjects without clinical evidence of thyroid cancer, from different regions of Italy, including areas of endemic goiter. We found 54 (10.65%) occult thyroid carcinomas. In 37 cases the histologic pattern was of the papillary type, with diameter ranging between 176 and 6000 microns, 12 of these cases showed a typical papillary pattern, 6 had a marked fibrosis, 2 had a cystic pattern, one showed a lymphoid stroma, and 17 had a follicular pattern. The remaining 17 cases were medullary carcinomas, with a diameter ranging from 50 to 1600 microns. The percentage of occult thyroid carcinomas reported in the present study may constitute real value of the occurrence of this tumor in the Italian population.

We have examined, by electron microscopy, the effect of glycosylation on binding, uptake, and transport of albumin-gold complexes in capillaries of isolated perfused rat lungs. Lungs were perfused for 2 min at 4 degrees with native and glycosylated albumin-coated gold particles. After the excess probe was washed out for 5 min the lungs were fixed immediately or perfused for 30 and 60 min at 37 degrees with a isoosmotic buffer before fixation. The localization and density of the probes over different microvascular endothelial compartments were determined by electron microscopy. We found that both native and glycosylated albumin were bound to the surface of the pulmonary microvascular endothelium, preferentially over the stomatal diaphragms of luminal smooth-walled vesicles. In both BSA and glycosylated BSA perfusions at 37 degrees, most of the probe was internalized and accumulated in lysosomes and only a few gold particles were observed in the extravascular compartment even after 60 min perfusion. However, binding, internalization, and transport of the protein-gold complexes was enhanced by nonenzymatic glycosylation of albumin.

The present study investigates 14 patients on intermittent haemodialysis. Pre-dialysis blood and muscle samples taken for determining plasma free- and acetylcarnitine levels. The tissue fragments were used for light and electron microscopy studies. Our results support the findings of other investigators that patients on haemodialysis generally display decreased free- and acetylcarnitine levels both in plasma and skeletal muscle when compared with control values. Muscle carnitine deficiency was apparently more severe in the longer-term haemodialysis patients. Moreover, a significant correlation (p less than 0.05) between plasma and muscle free-carnitine values was found. Morphologically no pathological alterations were observed in the muscle fibres in 13 of the patients. Light and electron microscopic studies of the muscle fibre of the 14th patient showed a typical nemaline myopathy with rod bodies in the cytoplasm. The muscle free-carnitine concentration in this patient was among the lowest of the group.

Tritiated thymidine radioautography was employed to study the effect of cortisol and other glucocorticoids on cellular proliferation in the aorta and pulmonary artery of rabbits with cholesterol atherosclerosis. Labelled cell counts showed that glucocorticoids, even after one day and at a relatively low dose, decrease sharply the deoxyribonucleic acid synthesis in the intimal plaques. The hormonal influence on [3H]thymidine uptake seems to be a dose-dependent process. The relative potency of these steroids in inhibiting DNA synthesis in the plaques parallels closely their anti-inflammatory effectiveness. Conversely mineralocorticoids, including aldosterone and deoxycorticosterone, increase the rate of DNA synthesis in the plaques. It is concluded that the antiatherogenic effect of glucocorticoids on cholesterol-fed rabbits may be due, at least partly, to the inhibitory effect of these steroids on the DNA synthesis of the cellular components of the intimal plaques.

A group of 14 uremic patients on intermittent hemodialysis was admitted to a cross-over double-blind trial in order to evaluate serum and muscle carnitine levels before and after 60 days of L-carnitine oral (2 g/day) treatment. The morphology of muscle fragments was studied by light and electron microscopy. Symptoms (asthenia, cramps) occurring during hemodialysis were also recorded. After L-carnitine treatment the blood and muscle levels of the metabolite increased simultaneously to reduced asthenia and cramps. Morphological examination of the muscle of 13 of 14 patients did not reveal any pre- or posttreatment pathological alterations. The presence of nemaline rods was morphologically diagnosed in only one case and was no longer observed at the second biopsy at 2 months of L-carnitine treatment.

Myo-endothelial contacts have been studied in rabbit carotid arteries. Structures, featuring as gap junctions, have been depicted by means of lanthanum hydroxide.

This study was undertaken to detect diagnostic ultrastructural changes in the alveolar walls in biopsies of patients with primary pulmonary hypertension (PPH). Open lung biopsies from 8 patients referred to the Hospital of the University of Pennsylvania were available for study. By light microscopy 4 patients were diagnosed as having plexogenic pulmonary arteriopathy, 2 thromboembolic arteriopathy and 2 veno-occlusive (PVOD) disease. In 4 patients the diagnosis of PPH was further confirmed at autopsy. Changes were observed in the basement membrane of the alveolar capillaries in 6 of the patients. These consisted in marked thickening and duplication of the basement membrane of alveolar capillaries in the 4 patients with the plexogenic form of pulmonary hypertension. Patients with PVOD instead showed uniform thickening of the basement membrane. No changes were detected in the 2 biopsies of patients with the thromboembolic form of PPH. We conclude that ultrastructural studies contribute significantly to the precise characterization of pathologic changes in the lungs of patients with PPH.

Electron microscopy and autoradiography with 3H-thymidine have been employed to study the cellular dynamic of intimal thickening occurring in the rabbit carotid artery after selective endothelial injury. The results obtained suggest that migration of SMC of the tunica media rather than proliferation is the key event in the development of the intimal thickening.

Human arterial biopsies were studied by morphometrical, cytochemical, autoradiographic and ultrastructural methods with the aim of determining whether intimal lesions in atherosclerosis are characterized by definite cytological patterns. The results have shown: 1. a strong association between fibro-atheromatous plaques and foam and monocyte-like cells; 2. very few foam cells in diffuse intimal thickening and pearly-white fibrous plaques; 3. macrophages and foam cells were the only cytotypes consistently labelled with 3H-TdR and presumably proliferating in the fibro-atheromatous plaques.

We have studied the kinetics of smooth muscle cell growth in the tunica media of human arteries obtained from 12 patients affected by obstructive vascular disease, and one case operated because of a trauma. The studies were carried out on arterial samples by autoradiography after in vitro labelling with 3H-thymidine. Different patterns of radioactive nucleotide uptake were detected. On nine elastic and muscular arteries without pathological changes it was demonstrated that the turnover of smooth muscle cells in human medias was very low, and similar to that found in experimental animals. The medias under atherosclerotic plaques showed variable levels of tritium uptake. Although the number of cases surveyed was limited, a possible explanation is that the different levels of uptake could depend on the different evolutive stages of the atherosclerotic process. It cannot, however, be excluded that the proliferative activity of the smooth muscle cells may be related to focal damages of the tunica media.