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Background Several environmental and seasonal factors are thought to be crucial in the risk of acute coronary syndromes (ACS), including temperature, latitude, longitude, atmospheric air pressure, wind velocity and circadian period. However differences in coronary plaque composition according to season variation is still poorly understood. Purpose. Our study aims to analyse the characteristics of non–culprit coronary plaques in patients undergoing optical coherence tomography evaluation (OCT) evaluation of the left anterior descending artery. Methods We included 1848 non–culprit coronary plaques from 1003 patients of the CLIMA registry. The season of OCT pullback acquisition was collected for each patient. Results Overall, median age was 66 years (56–74), with 24.6% of women and 53.4% of ACS. At patient–level analysis, patients admitted in summer were less frequently affected by hypertension (59.8% vs 69.4% in autumn, 68.5% in winter and 72% in spring; p=0.027) and chronic kidney disease (14.8% vs 15.9% in autumn, 10.3% in winter and 19.4% in spring; p=0.037) in. At lesion–level analysis, similar values of fibrous cap thickness, maximum lipid arc, length of plaques and presence of macrophages were observed (Table 1). Summer plaques had a smaller minimum lumen area than spring plaques (5.7±3.1 vs 5.1±239; p=0.044) and also a less frequent superficial macrophage infiltration (23% vs 36.1% in autumn, 30.5% in winter and 30.6% in spring; p=0.030) and presence of cholesterol crystals (16.7% vs 23.8% in autumn, 28.4% in winter and 22.1% in spring; p=0.037 than three other season). Conclusions Coronary plaques during summer had less local sign of inflammation such superficial macrophage infiltration and cholesterol crystals. Further studies are needed to confirm these results and investigate clinical implications.

Background Whether the addition of percutaneous microaxial flow pump Impella to venoarterial extracorporeal membrane oxygenation (VA-ECMO) as left ventricle unloading strategy is effective in improving outcomes compared to VA-ECMO alone is still to be proved. Purpose Aim of this systematic review and meta-analysis was to assess whether patients with refractory cardiogenic shock treated with IMPELLA in addition to VA-ECMO (ECMELLA) versus ECMO alone may benefit a reduction in early mortality and to assess whether this strategy may result in an increased rate of complications. Methods For this systematic review and meta-analysis, from Dec 2021 to Jan 2022, we searched Scopus, MEDLINE (with PubMed interface) and the Cochrane Central Register of Controlled Trials for randomised controlled trials and observational studies published in any language comparing the use of ECMELLA versus ECMO alone in patients with acute refractory CS (with or without cardiac arrest). Two independent investigators screened titles and abstracts for eligibility, extracted the data, and assessed risk of bias. Risk ratios (RRs) and 95% CIs were calculated with random-effects or fixed-effect models according to the estimated heterogeneity among studies assessed by the I2 index. Primary efficacy endpoint was trial-defined early mortality (in hospital or 30-day mortality). Safety endpoints were major bleeding, the need for renal replacement therapy, hemolysis, severe infections/sepsis and limb ischemia. This study is registered with PROSPERO (CRD42022292517). Results 2061 potentially relevant articles were screened. Our analysis included six retrospective studies with data for 1457 patients. Compared with ECMO alone, ECMELLA was associated with a non-significant reduction in early mortality (RR 0.87, 95% CI 0.72–1.06, p=0.17; Figure 1) and in a significant increase of major bleeding (RR 1.45, 95% CI 1.10–1.91, p=0.009), need for renal replacement therapy (RR 1.70, 95% CI 1.16–2.48, p=0.0008), hemolysis (RR 2.22, 95% CI 1.39–3.56, p=0.005) and limb ischemia (RR 1.61, 95% CI 1.20–2.16, p=0.001). No significant differences were observed in the incidence of severe infections/sepsis between the two groups (RR 1.23, 95% CI 0.97–1.58, p=0.09). (Figure 2) Conclusions The results of this meta-analysis showed that ECMELLA compared to ECMO alone did not significantly reduce early mortality and that, conversely, it resulted in a significantly increased risk of several complication (major bleeding, hemolysis, limb ischemia and renal replacement therapy). This study highlights that, if the benefit of left ventricle unloading with Impella during ECMO in CS shock is uncertain and probably limited to only selected patients, it surely increases the risk of some complications, therefore caution is needed in choosing such a strategy. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background. There are limited data about the intraprocedural hemodynamic study performed immediately before and after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). Purpose. We aimed to evaluate the acute hemodynamic impact of TAVI in patients with severe AS and to investigate invasive and non-invasive parameters predicting all-cause mortality. Methods. A total of 245 consecutive AS patients undergoing TAVI were enrolled. Intraprocedural left heart catheterization (LHC) and echocardiogram before and after TAVI were performed. The clinical endpoint was the death for any cause. Results. LHC after TAVI revealed significant changes in aortic and LV pressures, including indexes of intrinsic myocardial contractility and diastolic function such as positive dP/dT (1128.9 ± 398.7 vs 806.3 ± 247.2 mmHg/sec, p˂0.001; Figure 1A) and negative dP/dT (1310.7± 431.1 vs 1075.1 ± 440.8 mmHg/sec, p˂0.001; Figure 1B). Post TAVI echo showed a significant reduction in LV end diastolic volume index (54.6 ± 18.4 ml/m2 vs 51.7 ± 17.5 ml/m2; p = 0.017; Figure 1C), improvement in left ventricle ejection fraction (from 55 ± 12 to 57.2 ± 10.5%, p˂0.001; Figure 1D) and pulmonary artery systolic pressure (42.1 ± 14.2 vs 33.1 ± 10.7 mmHg, p FIGURE LEGEND Figure 1. A-B: Impact of TAVI on haemodynamic parameters: Box plot with median and interquartile ranges of positive dP/dT and negative dP/dT values pre vs post TAVI. C-D-E: Impact of TAVI on echocardiographic parameters: Box plot with median and interquartile ranges of left ventricular end diastolic volume index (LVEDVi), left ventricular ejection fraction (EF) and pulmonary artery systolic pressure (PASP) values pre vs post TAVI. Figure 2. Kaplan-Meier curves for survival showing that AR (2-3-4+) assessed with echocardiography had the strongest association with mortality. Abstract Figure 1. Abstract Figure 2.

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35–82) for the EVA and 57.8 years (range 35.0–82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1–48) and 12.4 months (range 2.9–70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Prescribed burning represents a serious threat to personnel fighting fires due to smoke inhalation. The aim of this study was to investigate exposure by foresters to smoke from prescribed burning, focusing on exposure to volatile organic compounds (VOCs). The methodology for smoke sampling was first evaluated. Potentially dangerous compounds were identified among the VOCs emitted by smoke fires at four prescribed burning plots located around Corsica. The measured mass concentrations for several toxic VOCs were generally higher than those measured in previous studies due to the experimental framework (short sampling distance between the foresters and the flame, low combustion, wet vegetation). In particular, benzene, phenol and furfural exceeded the legal short-term exposure limits published in Europe and/or the United States. Other VOCs such as toluene, ethybenzene or styrene remained below the exposure limits. In conclusion, clear and necessary recommendations were made for protection of personnel involved in fighting fires.

The effect of gender on the expression of primary hyperparathyroidism (PHPT) is not well characterized.We therefore evaluated two Caucasian populations (US and Italian) of men and women with PHPT, matched for age and body mass index (BMI), in a cross-sectional retrospective observational study.We studied 74 US (23 men) and 126 Italian (42 men) patients evaluating main biochemical indices of the disease and bone mineral density (BMD) at the spine and proximal femur.Mean serum calcium levels were higher both in Italian men compared to women (11.7 ± 1.22 mg/dl and 11.1 ± 0.83, p0.01) and in Italian compared to US patients (11.3 ± 1.01 and 10.8 ± 0.58, p0.001), with similar results for the serum ionized calcium. Mean serum PTH levels were not different either between the genders or between the countries. After controlling for BMI, the mean BMD at both the femoral neck and total hip in females US patients was significantly higher compared with Italian female patients.Despite similar levels of circulating PTH, Italian patients have more pronounced effects of the disease as assessed by serum calcium and a more significant cortical involvement in women as assessed by BMD.

This study was carried out in order to evaluate the effect of 18-month treatment with PTH (1-34) or PTH (1-84) on serum sclerostin levels in humans.We investigated 10 women with severe osteoporosis, previously treated with alendronate and 20 untreated osteoporotic women. Subjects with severe osteoporosis were randomly divided into 2 groups of 5 patients each; the first group was treated with 20 μg of PTH (1-34) and the second one with 100 μg of PTH (1-84) according to an open-label design. Fasting blood samples were collected at baseline and at 2, 4, and 24 h after hormone administration. The same protocol was followed at month 1, 6, 12, 18. Serum sclerostin levels were measured at each time point by a sandwich-type enzyme-linked immunosorbent assay.Basal serum sclerostin levels were not significantly different between patients previously treated with alendronate and those never treated. No significant acute change of serum sclerostin levels was observed after PTH administration. Fitting a mixed effect regression model, we found a significant time effect (p=0.0012) using the sclerostin level as the response variable and the month of drug administration as a single covariate. Treatment with both PTH molecules induced a monthly mean reduction of sclerostin levels of 0.1956 pmol/l.Our results indicate that long-term therapy with PTH (1-34) or PTH (1-84) in women with osteoporosis previously treated with alendronate is associated with a reduction in circulating sclerostin levels. This is a putative mechanism through which PTH performs its anabolic action.

The Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS) has elaborated the following guidelines about the definition, prevention and treatment of inadequate vitamin D status. The highlights are presented here. Daily vitamin D allowance ranges from 1,500 IU (healthy adults) to 2,300 IU (elderly with low calcium intake). Since the average Italian diet includes around 300 IU/day, subjects with no effective sun exposure should be supplemented with 1,200-2,000 IU vitamin D per day. The serum 25-hydroxy-vitamin D [25(OH)D] levels represents the most accurate way to assess vitamin D repletion, even though there are still no standardized assay methods. Conditions of “deficiency” and “insufficiency” are defined by the following ranges of 25(OH)D levels: less than 20 ng/ml and 20-30 ng/ml, respectively. In Italy, approximately 50% of young healthy subjects have vitamin D insufficiency during the winter months. The prevalence of deficiency increases with ageing, affecting almost all elderly subjects not on vitamin D supplements. When a condition of deficiency has been identified, a cumulative dose of 300,000-1,000,000 IU, over 1-4 weeks is recommended. In subjects recently treated for deficiency-insufficiency, a maintenance dose of 800-2,000 IU/day (or weekly equivalent) is recommended. In patients on daily doses over 1,000 IU, 25(OH)D levels should be checked regularly (e.g. once every two years). The highest tolerated daily dose has been identified as 4,000 IU/day. Vitamin D supplementation should be carefully monitored in patients at higher risk of vitamin D intoxication (granulomatosis) or with primary hyperparathyroidism. In pregnant women, vitamin D supplements should be given as in non-pregnant women, but bolus administration (i.e.: single dose25,000 IU) should be avoided.

Canine cryptorchidism is a congenital defect that results from sex-limited autosomal recessive gene(s). Incidence is higher in some breeds, especially in smaller and inbred ones. Parents of affected puppies are carriers. Unilateral cryptorchid dogs can be fertile, and affected individuals and their siblings should be eliminated from a breeding program to decrease incidence of the defect. Androgen and gonadotropin treatments have been tried with little or no success. Bilateral orchidectomy is the treatment of choice because of the common sequelae of testicular neoplasia and torsion.

Primary hyperparathyroidism (PHPT) is characterized by excessive PTH secretion in respect to calcium homeostasis needs, due to parathyroid adenoma (80% of cases), hyperplasia (15-20%), or carcinoma (1-2%). In familial forms of PHPT, several mutations have an established role: menin gene for MEN type 1, RET for MEN type 2a, calcium-sensing receptor gene for familial hypocalciuric hypercalcemia, parafibromin gene for PHPT-jaw tumour and carcinoma. Etiology of sporadic adenomas (80% of PHPT cases) is less defined, being most commonly found a mutation of menin gene or activation of PRAD1 oncogene. In recent years, the classical features of the disease became less common. Typically, bone involvement is now represented by a reduced bone mass at skeletal sites more rich in cortical tissue. Prominently trabecular skeletal sites are relatively spared, because of the anabolic effects of a slight PTH excess on trabecular tissue. PHPT patients may have increased fracture risk, though it is not clear why bone damage is more severe in a subgroup of patients. Clinical features of hypercalcemia may be fatigue, anorexia, thirst, and polyuria. Vague neurological and psychiatric symptoms, such as weakness, anxiety, depression, paresthesias, and muscular cramps may ameliorate after parathyroidectomy. Recent reports indicate increased cardiovascular mortality in PHPT patients. Diagnosis is based on the detection of hypercalcemia, together with inappropriately high serum PTH levels. Preoperative localization of the diseased glands is mandatory in persistent or recurrent PHPT, as like as when minimally invasive surgery is planned. High resolution ultrasonography and SPECT double-phase 99m Tc-sestamibi scintigraphy are the most commonly employed techniques. Intraoperatory PTH assay may confirm successful surgery when serum concentrations decrease more than 50%. Surgical therapy is indicated in patients with renal or skeletal complications, such as in those with previous parathyrotoxic crisis. Many surgeons in recent years adopted minimally invasive parathyroidectomy. Medical treatment is an option for patients unwilling or unfitted for surgery because of severe concomitant diseases. Employed therapy includes estrogens, SERMs, bisphosphonates and calcimimetics.

Summary form only given. The major issue today on cluster and grid computing is the efficient resource management. The evaluation of scheduling strategies is hard because of the generation of jobs under realistic scenario. This is true for rigid jobs (where the number of processors is fixed) and even more for moldable ones. We present an approach to generate realistic workloads for this kind of jobs. The model we propose is based on the analysis of one year of utilization of the I-cluster, a 225 processors cluster. From this log we extract a typical load for this kind of parallel machines and introduce a way to generate synthetic realistic workloads in an automatic way. This work was done as a way to test scheduling strategies taking into account both rigid and moldable jobs so as the workload generator may handle moldable jobs.

To provide indications for currently approved treatments and future options for male osteoporosis, based on the pathogenetic mechanisms of bone loss in the male sex.Review of the most significant data reported in the literature.Unhealthy lifestyle habits should be modified. Testosterone replacement is indicated only in patients with diagnosis of hypogonadism. Based on the demonstrated pathogenetic role of estrogen lack in bone loss in men, either low doses of this hormone or selective androgen receptor modulators have been proposed for the treatment of male osteoporosis. Bisphosphonates are the only medications approved by Food and Drug Administration for idiopathic and glucocorticoid-induced osteoporosis in men. As far as anabolic treatments are concerned, there is not agreement on clinical utility of sodium fluoride. Short-term treatment with parathyroid hormone (PTH) seems to be safe and effective in patients with idiopathic osteoporosis, due to its anabolic action. Therapeutic use of growth hormone (GH) and insulin-like growth factor type I (IGF-I), both considered as potential anabolic agents, is still limited because of the high incidence of side effects and relatively transient efficacy, particularly of IGF-I.Treatments should be selected on the basis of anti-fracture efficacy of various medications, which has been demonstrated so far only for alendronate and risedronate. Although anabolic agents produce noticeable increase of bone mineral density, is still debated if they also reduce fracture incidence in males with osteoporosis.

An excess of glucocorticoids is the third most common cause of bone loss after postmenopausal and senile osteoporosis. The iatrogenic form of glucocorticoid-induced osteoporosis, which is more frequent than Cushing syndrome, has uncertain cellular and molecular bases. The lack of consistent information concerning the pathophysiology of corticosteroid-related bone loss is attributable to several coexisting factors, e.g., the heterogeneity of the underlying disease, that may themselves influence skeletal loss, dosage, and duration of treatment (1)(2). A well-known action of steroids on bone is decreased bone formation. There are no consistent findings concerning bone resorption in glucocorticoid-induced osteoporosis. The aim of this study was to evaluate the impact of a short period of steroid therapy on the serum concentrations of bone biomarkers in elderly men. We studied 14 elderly men (mean age ± SD, 66.1 ± 6.4 years; range, 57–76 years), admitted to our hospital from October 1998 to June 1999, who were suffering from various medical pathologies requiring systemic steroid therapy. Four patients were suffering from pulmonary diseases, four from immunologic, two from cerebral, and four from neoplastic diseases without bone metastases. None of these patients was bedridden. The patients were studied while undergoing treatment, which lasted no more than 30 days (mean ± SD, 9.1 ± 9.6 days), with a cumulative dose of 10–1250 mg of prednisone (mean prednisone equivalent, 338 ± 382 mg) or its equivalent. The patients were compared with 14 hospitalized patients of similar age (67.9 ± 6.7 years) without any history of …

Enzymatic and molecular cytochemistry was used to detect and follow the hepatotoxic effects caused in overnight-fasted Sprague-Dawley rats by a 1-h continuous intrafemoral infusion of taurochenodeoxycholate at 0.4 and 0.8 mumol-1 min-1 100 g-1 body weight dose levels. Rats were killed at 0, 1 and 24 h from the end of perfusion. Their livers were examined for morphology, DNA fragmentation (by a TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labelling assay), cell regeneration (by in vivo bromodeoxydurine incorporation), reduced glutathione, calcium and several enzyme cytochemical activities. Isolated injured hepatocytes randomly scattered throughout the liver were already evident at the end of perfusion. DNA fragmentation and cytoplasm shrinkage were prominent and early features of injured hepatocytes, which later showed calcium loading and chromatin clumping. Preserved cytochemical enzymatic activities indicated that plasma and mitochondria membranes were not severely damaged. Inflammatory response was absent. These observations indicate that an acute exposure to taurochenodeoxycholate induces a cell death process with apoptotic features.

Records of elective abortion in 27 bitches presented to the Veterinary Surgery and Reproduction Clinic of the University of Pisa were reviewed. Treatment consisted of twice-daily subcutaneous injections of 150-270 micrograms natural prostaglandin F2 alpha kg-1 for 4 consecutive days starting between cytological dioestrous days 5 and 19. None of the treated bitches whelped. Luteolysis appeared to be complete (serum progesterone3.2 nmol l-1) at the end of treatment in 22 of 25 bitches in which progesterone was assayed in serum obtained daily during therapy. Serum progesterone rose after treatment to a concentration consistent with pregnancy in four of 17 bitches in which progesterone was measured once between dioestrous days 23 and 51. The mean intercycle interval (pro-oestrus-pro-oestrus) of the cycle in which abortion was induced was 134 +/- 45 days for 15 dogs for which the interval could be determined, and was significantly shorter than the average preceding interoestrous intervals (210 +/- 40.0 days) for the same dogs (P0.001).

A method is described for separating and quantifying new cephalosporin derivatives by means of column chromatography on DEAE-Sephadex A-25. The procedure has been used to determine some breakdown products of cefacetril.

Two yearling, paternal half-sibling Appaloosa fillies were ovariohysterectomized for treatment of multiple uterocervical leiomyomas. The tumors recurred in both fillies, originating from cervical tissue that could not be removed at surgery. Previously reported cases of uterine leiomyoma in the mare have been of solitary tumors in older mares that were treated successfully by surgical removal.

The aim of the study was the evaluation of plasma osteocalcin (O.), alkaline phosphatases (A.P.) and urinary hydroxyproline excretion (uOHPr) in subjects 3-20 years aged. O., A.F. and uOHPr were increased in patients less than 15 years aged; thereafter the values were similar to normal adult values. O. correlates with age and body surface area in children aged less than 15 years; the highest values were observed at the expected age of puberal spurt. This behaviour was not evident for the other bone turnover markers studied. In conclusion, it could be suggested that O. is a useful index of bone peak mass reached at puberty.