Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry).

BACKGROUND AND AIMS: Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR. METHODS: ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0-30 days), late (31-180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC). RESULTS: Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 [95% CI, 0.0431-0.0506] vs 0.0179 [95% CI, 0.0174-0.0185]; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 [95% CI: 0.0417-0.0477] vs 0.0642 [95% CI: 0.0557-0.0728]; p < 0.001*, ADBR 0.0395 [95% CI: 0.0381-0.0409] vs 0.0147 [95% CI: 0.0138-0.0156]; p < 0.001*). CONCLUSIONS: In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.

Impact of the COVID-19 pandemic on hospitalizations for acute coronary syndromes: a multinational study.

BACKGROUND: COVID-19 has challenged the health system organization requiring a fast reorganization of diagnostic/therapeutic pathways for patients affected by time-dependent diseases such as acute coronary syndromes (ACS). AIM: To describe ACS hospitalizations, management, and complication rate before and after the COVID-19 pandemic was declared. DESIGN: Ecological retrospective study. Methods: We analyzed aggregated epidemiological data of all patients > 18 years old admitted for ACS in twenty-nine hub cardiac centers from 17 Countries across 4 continents, from December 1st, 2019 to April 15th, 2020. Data from December 2018 to April 2019 were used as historical period. RESULTS: A significant overall trend for reduction in the weekly number of ACS hospitalizations was observed (20.2%; 95% confidence interval CI [1.6, 35.4] P = 0.04). The incidence rate reached a 54% reduction during the second week of April (incidence rate ratio: 0.46, 95% CI [0.36, 0.58]) and was also significant when compared to the same months in 2019 (March and April, respectively IRR: 0.56, 95%CI [0.48, 0.67]; IRR: 0.43, 95%CI [0.32, 0.58] p < 0.001). A significant increase in door-to-balloon, door-to-needle, and total ischemic time (p <0.04 for all) in STEMI patents were reported during pandemic period. Finally, the proportion of patients with mechanical complications was higher (1.98% vs. 0.98%; P = 0.006) whereas GRACE risk score was not different. CONCLUSIONS: Our results confirm that COVID-19 pandemic was associated with a significant decrease in ACS hospitalizations rate, an increase in total ischemic time and a higher rate of mechanical complications on a international scale.

Fluorescence-determined kinetics of plasma high oxidability in diabetic patients.

The peroxidative potential of whole plasma was studied in thirteen control subjects and twenty-three diabetic patients divided into two groups on the basis of their metabolic control, defined as good (n = 12) or poor (n = 11) according to the fasting blood glucose, glycated hemoglobin and fructosamine levels. The amounts of thiobarbituric reactive substances (TBARS) were determined before and after an exhaustive peroxidation induced by incubation with cupric sulfate; the kinetics of Cu-dependent plasma peroxidation, determined by the time course of endogenous fluorescence emission at 430 nm, were also evaluated. Our data indicate that in diabetic patients, and particularly in those with a long-lasting poor metabolic control, a significant increase in plasma susceptibility to peroxidative stress is evident only when we consider the lag-time of fluorescence emission in the course of Cu-induced plasma peroxidation. A good inverse correlation was observed between the lag-time and the blood glucose concentration, the glycated hemoglobin and the fructosamine blood levels. Furthermore a multivariate analysis, performed by Principal Component Analysis, strongly supports the relation between the extent and duration of the diabetic pathology, and the decrease in the lag-time of oxidation.

A clinical assessment of the potential for pharmacological interaction between nimesulide and digoxin in patients with heart failure.

The potential interaction between nimesulide, a nonsteroidal anti-inflammatory drug, and digoxin was studied in 9 patients [6 males, 3 females; mean age 67 (range 57 to 70) years] with mild heart failure. All patients were receiving maintenance therapy with digoxin (0.25 mg/day, orally) and were treated with oral nimesulide 100mg twice daily for 7 days. Blood samples were collected at 8am and 6pm for 4 days before and throughout the nimesulide treatment period for determination of serum digoxin concentrations. Physical health, electrocardiographic recordings and blood and urine samples were also monitored. Mean serum digoxin concentrations remained within the normal therapeutic range throughout the study despite large interindividual variation. Furthermore, there were no significant differences between the morning and afternoon serum digoxin concentrations and there was no major change in the clinical condition of any patient. These results indicate that short term administration (7 days) of conventional therapeutic doses of nimesulide (100mg twice daily) does not modify the serum digoxin profile in patients with low class heart failure treated with a maintenance dose (0.25 mg/day) of this cardiac glycoside.

Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia.

Ninety-eight type 2 diabetic patients with hyperlipidaemia in stable metabolic control with diet alone (41) or diet plus hypoglycaemic agents (57) were divided into two groups: group 1 was put on treatment with slow release bezafibrate 400 mg a day, while group 2 was considered as control. In group 1, after 1 month of bezafibrate, serum triglycerides fell by 47% and cholesterol by 13%. HDL cholesterol showed a non-significant trend toward an increase. Fasting blood glucose significantly decreased by 6%, fructosamine and glycated haemoglobin by 5%. During OGTT, the area under the curve of both serum C-peptide and blood glucose showed a trend toward a decrease after bezafibrate. However, the difference did not reach statistical significance. Thirty-six patients continued the treatment with the drug for 4 months and 23 for 8 months, without further changes of the lipid pattern and glycaemic control. In the control group no significant variation of the lipid levels occurred and diabetic control slightly worsened during the study. Bezafibrate has been proved to be effective in the treatment of hyperlipidaemia in type 2 diabetic patients. The drug seems moreover to improve glycaemic control. The mechanism by which bezafibrate produces this latter effect remains to be elucidated, though an increase of peripheral insulin sensitivity might be suggested.

First dose and steady state pharmacokinetics of nimesulide and its 4-hydroxy metabolite in healthy volunteers.

The pharmacokinetics of nimesulide (4-nitro-2-phenoxymethane-sulfonanilide, NMS), a non-steroidal antiinflammatory drug, and of its 4-hydroxy metabolite (4-nitro-2-(4'-hydroxy-phenoxy)-methane sulfonanilide, OH-NMS) was studied after a single oral dose (200 mg) and after repeated treatments (100 mg every 12 hours for 7 days) of NMS to two groups of 12 healthy volunteers. Plasma concentrations of NMS and OH-NMS were followed for 48 hours after the single dose and up to the 12th hour on the 1st day and on the 7th day during repeated treatment. After the single dose of 200 mg peak plasma concentrations of the drug (9.85 micrograms/ml) were reached at 3.17 hours and the half-life during the elimination phase was 4.95 hours. The metabolite reached highest plasma levels (3.03 micrograms/ml) at 5.33 hours and its apparent half-life was similar to that of the parent drug (4.78 hours). NMS plasma levels on the 7th day, predicted from the results of the 1st day, were similar to the measured values. The pharmacokinetics of NMS or OH-NMS after single or repeated dose was not time or dose dependent.

[Surgical therapy of liver metastases secondary to colorectal neoplasms]. / Considerazioni sulla terapia chirurgica delle metastasi epatiche secondarie a neoplasia colo-rettale.

Of the therapeutic aids currently available for the treatment of liver metastases, surgical treatment, when possible, has acquired an irreplaceable role. The exact criteria needed to establish a correct indication still have to be established. Various factors have been examined so far: number, site, dimensions of the metastases and features of the primary tumour whose prognostic importance does not lend itself to unequivocable interpretation. Personal experience of a series of 11 surgically treated cases seems to confirm that of the parameters analysed, the tumour-host relationship remains the most important prognostic factor.

[Grade II and III acute pancreatitis. Diagnostic classification and surgical treatment]. / Pancreatite acuta di II e III grado. Inquadramento diagnostico e trattamento chirurgico.

Thirteen cases of acute IIIrd degree pancreatitis and 5 homogeneous cases of IInd degree, treated surgically during the first 48 hours from onset of the symptomatology, are described. The importance of careful cardiorespiratory, haemodynamic and metabolic monitoring to establish the most appropriate moment for intervention after a period of intensive therapy designed to restore the basic parameters is stressed. In the present series, total mortality was 44%. Forms with biliary aetiology have the best prognosis and justify the earliest possible surgical intervention.