Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19.

BACKGROUND: Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19. METHODS: A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm). RESULTS: Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups. CONCLUSIONS: Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients. TRIAL REGISTRATION: The study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

Neuroendocrine predictors of vasoplegia after cardiopulmonary bypass.

PURPOSE: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. METHODS: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. RESULTS: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73-0.94; OR 1.17, 95% CI 1.04-1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8-0.93; p < 0.001). CONCLUSION: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.

Visceral leishmaniasis in hematopoietic cell transplantation: Case report and review of the literature.

Visceral leishmaniasis has been recognized as an opportunistic infection affecting people with cellular-immunity impairment, including hematopoietic cell transplantation (HCT) recipients. We describe the case of a young Italian man with Hodgkin lymphoma, who developed visceral leishmaniasis after multiple lines of chemotherapy and allogenic HCT. Literature review of visceral leishmaniasis in HCT recipients was also performed. Eleven patients (median age 50 years, 9 male) developed visceral leishmaniasis after allogenic (n = 9) and autologous (n = 2) HCT. Most of them presented with fever and pancytopenia. Bone marrow examination was the main diagnostic technique; liposomal amphotericin B was the treatment of choice. Four out of eight patients (for whom data are available) experienced visceral leishmaniasis relapse. Visceral leishmaniasis in HCT recipients is a rare event that should be suspected in patients with persistent fever, pancytopenia and possible exposure to Leishmania spp., remembering that - as well as South-East Asia, East Africa and South America - it is endemic in several European regions.

[Chronic bacterial endocarditis on the electrical catheter in a pacemaker wearer: a clinical case report]. / Endocardite batterica cronica su elettrocatetere in portatore di pacemaker: descrizione di un caso clinico.

This article reports a case of infective endocarditis in a patient with a permanent pacemaker 15 months after the generator had been replaced. The patient had Staphylococcus epidermidis isolated in several blood cultures. No interventional or clinical procedure with any risk of bacteremia was performed, nor was any infective complication of the pocket observed. Thus, the portal of entry of the etiologic agent is unclear. The role of transesophageal echocardiography in detecting pacemaker-induced endocarditis is very important and therapy of choice involves removal of the pacemaker system as soon as possible.

Major vertebral surgery: intra- and postoperative anaesthesia-related problems.

A personal experience concerning vertebral excision and resection in a single stage for neoplasm is discussed. The surgery requires anaesthesia of long duration, hemodynamic stability, compensation of significant blood loss, monitoring of heat loss, maintenance without injury of prolonged prone position. Experience, with 24 cases lasting an average of 14.5 hours proves that inhalation or intravenous anaesthesia with a strong analgesic component is satisfactory. Normal heat saving systems reduce intraoperative hypothermia. Transfusion is always abundant, autologous contribution is moderate. Hemodilution is well-tolerated up to Hb 7%; below this amount there may be problems of a hemodynamic and coagulative nature. The quantity and quality of filling is guided by monitoring of pre-loading pressures and availability of oxygen. There were no critical complications; all of the patients left the hospital in good condition.

[Short and intermediate term clinical outcome in patients with cardiogenic shock treated with aortic counterpulsation]. / Evoluzione clinica a breve e medio termine di pazienti cardiopatici in shock cardiogeno trattati con contropulsazione aortica.

BACKGROUND: Despite improvements in coronary care, cardiogenic shock (CS) remains the leading cause of death in patients with dramatic cardiac diseases of which acute myocardial infarction (AMI) is the most frequent event. Conventional therapy for CS with coronary care unit (CCU) monitoring and vasopressor agents to support blood pressure has historically been associated with an 80% to 90% mortality rate in large series. Intra-aortic balloon pump (IABP) therapy for shock results in initial favourable clinical and haemodynamic responses, but ultimately, in most patients, death is merely delayed and hospital mortality still exceeds 80%. In several recent non-randomised series, coronary revascularisation performed early in the course of CS with the use of coronary artery by-pass grafting (CABG) or coronary angioplasty (PTCA) resulted in an apparent reduction in the hospital mortality rate to less than 50% in selected patients with shock. OBJECTIVES: This study reviews our experience of cardiogenic shock treatment at a time when standard care included aggressive use of the intra-aortic balloon pump counterpulsation, cardiac catheterisation, coronary angioplasty and/or coronary artery by-pass grafting, ventricular septal defect and mitral incompetence repair. METHODS: We retrospectively analysed 20 patients (13 M and 7 F, with an average age of 62 years and a half) affected by cardiogenic shock consecutively admitted to our CCU between October 1, 1992 and April 1, 1995. Fifteen patients (pts) were hospitalised for AMI, shock and pump failure (2 of them with pulmonary oedema), all with admittance delay less than 24 hours. Five patients were hospitalised for AMI with shock and mechanical defects, of which 3 pts with AMI and ventricular septal rupture and 2 pts with AMI and mitral regurgitation. All patients underwent IABP, coronary angiography (CA) and then were treated with PTCA, CABG and cardiac surgery or medical treatment. RESULTS: On the whole, 7 pts died (35%): 4 of shock, 1 of haemorrhagic complications, 1 of septic shock in the CCU, and 1 of heart failure after CABG in cardiosurgery. One more patient died of heart failure two months after discharge (late mortality 5%). Out of the 15 patients hospitalised with AMI, shock and pump failure, 13 patients with AMI and CS less than 24 hrs were treated as follows: 1 patient was successfully submitted to emergency CABG and 12 patients to PTCA of the infarct related artery (IRA). Eight patients enjoyed a good outcome, but 1 patient died of haemorrhagic complications and 4 with a persistently occluded IRA also died (3 in the CCU and 1 after CABG). Of the 2 remaining pts with AMI, shock and pulmonary oedema, 1 patient underwent CABG with success and 1 patient with the 3-vessel disease was submitted to PTCA with reperfusion of the IRA, but he died from reocclusion three days later. Out of the 5 patients with AMI, shock and mechanical defects, 3 patients with AMI and septal ventricular rupture underwent cardiac surgery and CABG with early and late success. One of the 2 patients with AMI, shock and mitral regurgitation underwent cardiac surgery with valve repair and CABG and had a good outcome, the other died from septic complications in the CCU. CONCLUSIONS: IABP is an useful device for stabilising patients in cardiogenic shock and safely performing angiography as well as PTCA, CABG or surgical correction of all mechanical complications with a more stable haemodynamic balance. Therefore, IABP is an useful tool to improve successful coronary revascularisation after direct PTCA or direct CABG. These data also suggest that the combination of successful coronary revascularisation and intra-aortic balloon pumping can improve survival in pts with cardiogenic shock complicating AMI with early pump failure.

[The recurrence of pulmonary embolism during heparin therapy after thrombolysis in the acute phase: a clinical case report]. / Recidiva di embolia polmonare in corso di terapia eparinica dopo trombolisi in fase acuta: descrizione di un caso clinico.

We report a case of a 61-year-old woman admitted to our Coronary Care Unit for pulmonary embolism following cholecystectomy. After thrombolytic therapy, and during treatment with heparin (administered as a continuous intravenous infusion in the standard dose), the patient had a recurrence of pulmonary embolism and a subsequent implant of a Gianturco-Rohem vena cava filter. The patient presented an initial reduction in the number of platelets from 477 x 10(3)/microliters to 360 x 10(3)/microliters that was ascribed to a heparin side effect or to a blocking of the platelets in a massive pulmonary thrombosis. A predischarge platelet count, however, showed an elevated number of thrombocytes (944 x 10(3)/microliters) and hyperfibrinogenemia (fibrinogen = 750 mg/dl). Essential thrombocythemia was demonstrated and treated with interferon alpha-2b-recombinant 3,000,000 U.I. on alternate days with a reduction in platelets to 450 x 10(3)/microliters. This case demonstrates the necessity of exploring, during pulmonary embolism, all possible causes of hypercoagulability in the course of thrombolytic therapy.

Indobufen in the prevention of thromboembolic complications in patients with heart disease. A randomized, placebo-controlled, double-blind study.

BACKGROUND: The purpose of this randomized, double-blind study was to evaluate the efficacy of indobufen, a reversible inhibitor of platelet cyclooxygenase, in the prevention of embolic events of cardiac origin. METHODS AND RESULTS: One hundred ninety-six patients with heart disease and at risk for cardiogenic embolism (90 with atrial fibrillation and 106 in sinus rhythm) were randomly assigned to receive indobufen (100 mg b.i.d.) or placebo. All patients were reexamined every 3 months for the duration of the study. The primary study end points were cerebral ischemic attack (stroke and transient ischemic attack), systemic embolism, pulmonary embolism, and fatal myocardial infarction. The median duration of treatment was 854 days in the indobufen group and 865 days in the placebo group. The frequencies of primary end points (fatal and nonfatal) were 6.1% and 17.3%, respectively, in the indobufen and placebo groups (p < 0.05) for a reduction of 65% in the risk of a primary event (indobufen/placebo relative risk, 0.35; 95% confidence limits, 0.14-0.89). Adverse drug reactions, mostly gastrointestinal or hemostasis disorders, occurred in 9.2% of indobufen-treated patients. CONCLUSIONS: The results of the study indicate that indobufen may reduce the risk of ischemic events in patients with heart disease associated with an increased risk of embolism.

[Integration of the hospital coronary care unit with the first aid service for the domiciliary treatment of cardiovascular emergencies]. / Integrazione dell'unità coronarica ospedaliera con la guardia medica per il trattamento domiciliare delle urgenze cardiovascolari.

To evaluate the feasibility and the utility of an integrated service for the pre-hospital diagnosis and care of cardiovascular emergencies a new pre-hospital intensive care system has been developed. Such an emergency medical service relies on the telephone transmission of ECG and the conversation between the first aid service and the cardiologist of the hospital coronary care unit. It also implies early therapeutic intervention performed at home under the responsibility of the chief physician of the referring centre. From March '86 to December '88, 311 telephone ECG transmissions were obtained; the home diagnosis and the consequent proper therapeutic regimen were considered sufficient to avoid the transportation of the patient to the hospital emergency room in 43% of the cases. The symptoms were: precordial chest pain (54%); palpitations (10%); dyspnea (8.4%); hypertensive crisis (1.3%), dizziness or syncope (12.3%). Pre-surgical or organ transplantation controls totaled 13.5%. One-hundred-forty-eight patients were admitted to the coronary unit because of an acute myocardial infarction between June and December 1988. Forty-seven patients were sent by the family doctor (group I) and 30 patients by the first aid service (group II) without any electrocardiographic diagnosis or home therapy; 14 patients were sent by the first aid service after a telephone transmission of ECG and early therapeutic intervention (group III); 57 patients reached the hospital independently (group IV). The following differences among the groups were observed: only the patients of group III received proper early therapeutic regimen at home, and 85% were admitted within 4 hours of the onset of symptoms (vs 46% of the patients of the other groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained beneficial hemodynamic effects of low transdermal nitroglycerin doses compared with placebo in patients with congestive heart failure.

In an attempt to resolve some of the controversies concerning the dose requirements and duration of effects of transdermal nitroglycerin (NTG) in patients with heart failure (CHF), the short-term hemodynamic responses to transdermal NTG, in a 20 cm2 self-adhesive patch (10 mg/24 h), were evaluated in 10 patients with severe chronic CHF using a randomized, within-patient, double-blind, placebo-controlled cross-over trial. Serial hemodynamic measurements over 24 h revealed sustained effects that began 1 h after the application of nitroglycerin patch and fully persisted throughout the study. The peak effect occurred at 4 h with the pulmonary capillary wedge pressure decreasing from 33.7 +/- 8.4 to 21.4 +/- 9 mmHg (mean +/- SD) (p less than 0.05) and the cardiac index increasing from 2.5 +/- 0.6 to 3 +/- 0.6 l/min/m2 (p less than 0.01). Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures (from 43.5 +/- 9.5 to 31 +/- 11.4 and from 7.4 +/- 6.6 to 3.8 +/- 4.7 at peak effect, respectively) as well as pulmonary and systemic vascular resistances (from 10.7 +/- 6.6 to 6.5 +/- 3.2 and from 26.2 +/- 5.1 to 22.5 +/- 5.7, respectively). There was no change in heart rate or systemic arterial pressure. These beneficial hemodynamic responses persisted for 24 h. No rebound deterioration occurred upon withdrawal of the nitroglycerin. No significant hemodynamic changes occurred during placebo treatment period. Thus, low doses (10 mg/24 h) of transdermal nitroglycerin induce significant hemodynamic benefit that is sustained for 24 h in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacological and clinical research on the interaction of digitalis and amiodarone in heart disease patients with varying degrees of cardiac insufficiency]. / Ricerca farmacologico-clinica sull'interazione digitale-amiodarone in pazienti cardiopatici con insufficienza cardiaca di vario grado.

The increasing use of amiodarone as antiarrhythmic drug has raised the possibilities of dangerous effects from amiodarone-digitalis interaction. We have studied twelve patients who were taking digitalis and to whom amiodarone was administered because of arrhythmias. We found a 75,42% increase of digitalis plasma levels (p less than 0,001) in the early days of amiodarone therapy, and a 52,1% increase (p less than 0,001) in the medium term. An inverse correlation was found (r = -0,65; p less than 0,05) between the plasma levels of digitalis during the steady-state control period and during the following 2-to-6 months evaluation. Acute episodes of cardiac failure caused in our patients an abrupt increase of digitalis plasma levels: in three patients digitalis toxicity occurred. Based on our experience, we recommend that the dose of digitalis be halved when the two drugs are given together in patients with various degree of cardiac failure; moreover digitalis plasma levels should be frequently monitored in these patients. On the other hand digitalis administered according to age, sex, weight, kidney function, together with amiodarone, can be given at full dosage in patients without cardiac failure.

[Correlations among the haemodynamic effects in acute myocardial infarction. Function evaluation and prognosis 12 months later (author's transl)]. / Correlazioni tra i valori emodinamici, la fase acuta, l'evoluzione funzionale e la prognosi a 12 mesi nell'infarto miocardico.

The hemodynamic monitoring of acute myocardial infarctions has been carried out in patients less than 75 y.o. who showed: a) extensive anterior myocardial infarction; b) inferior myocardial infarction and ST segment depression of the anterior chest leads; c) acute myocardial infarction and cardiac failure. The hemodynamic measurement were carried out at the 12 hours (mean) from the beginning of chest pain on 65 patients who suffered the first myocardial infarction and were protracted to 60 hours (mean). The hemodynamic findings were classified according to the relationship between the stroke work index of the left ventricle (LVSWI) and the mean pulmonary artery pressure (MPAP) as following: normals: 6 pts; hypovolemia: 15 pts; reduced compliance: 2 pts; mild LV failure: 19 pts; severe LV failure or shock: 23 pts. 35 pts have carried out a complete rehabilitation programme has shown an inverse linear relationship to the MPAP of the first recording in CCU. The incidence of death was 29% one year after the myocardial infarction and showed a significant relationship to the hemodynamic findings. The LVSWI resulted more sensitive than MPAP; 90% of patients who showed a LVSWI less than 20 gmb/m2 died.