Improvement in health status and quality of life in patients with osteoporosis treated with denosumab: results at a mean follow-up of six years.

OBJECTIVE: The clinical efficacy and tolerability of denosumab in severe osteoporosis are well-known. However, the evaluation on general health and quality of life over time and compared to population norms is still lacking. We aimed at evaluating denosumab effectiveness in a real-world clinical sample with a 6-years average follow-up. PATIENTS AND METHODS: In this retrospective-matched study with prospective data collection, a total of 101 patients affected by severe osteoporosis and treated with denosumab between 2014 and 2020 were evaluated. All patients completed the self-perceived quality of life (36-Item Short Form - SF-36) survey and visual analogue scale (VAS) before and after treatment. RESULTS: Overall, 13 patients died of causes unrelated to the procedure, 12 stopped therapy with denosumab, and 30 did not participate in the follow-up; thus, 46 patients completed the study. There were 44 (95.7%) women and 93.4% of patients reported history of osteoporotic fractures. The mean follow-up was 59±17.8 months and the mean age at follow-up was 73.9±10.6 years. We found a significant improvement in bodily pain (baseline 53.8±33.4, follow-up 62.7±26.6; p=0.002) and in general health (baseline 35±25.4, follow-up 41.7±24.2; p=0.002) over time. The bodily pain score at follow-up was similar to the mean of the age-matched healthy population (62.7±26.6 vs. 67.6±26, p=0.374). The MCS-36 scores were higher than the normative values before treatment and at follow-up (51.6±9.8 vs. 45.8±9, p=0.004 and 50.6±11.7 vs. 45.8±9, p=0.030, respectively). The PCS-36 score at follow-up was comparable to the normative values (39.4±10.4 vs. 42.7±9, p=0.107). CONCLUSIONS: Denosumab is effective to improve bone health and global mental and physical wellbeing, and quality of life over time.

Patent side branches do not affect coronary blood flow in internal thoracic artery-left anterior descending anastomosis: an experimental study.

BACKGROUND: It has been reported that large side branches of internal thoracic artery grafts may steal flow from the coronary circulation. Material an. METHODS: To assess the importance of the side branches, we measured the proximal and distal flow and pressures (mean subclavian artery pressure and mean arterial anastomotic pressure) at baseline and during infusion of adenosine (0.5 mg/kg/min) in 10 Landrace pigs in which an internal thoracic artery-left anterior descending anastomosis was constructed without interruption of the side branches. The difference between proximal and distal flow was considered to represent the blood flow of the internal thoracic artery side branches. Measurements were then repeated after surgical occlusion of all the side branches. RESULTS: At baseline, blood flow of the side branches represented 18% of the total flow in the proximal internal thoracic artery, and this percentage remained constant under the infusion of adenosine, which caused a 220% increase of the cardiac index and a 368% increase of the proximal flow. The infusion reduced the gradient along the left internal thoracic artery (mean subclavian artery pressure-mean arterial anastomotic pressure) from 15 to 10 mm Hg (P =.02) as the result of a lower mean subclavian artery pressure, although the mean arterial anastomotic pressure remained constant. Interruption of all the side branches resulted in a small and not significant increase in distal flow even after adenosine infusion. CONCLUSION: These observations suggest that blood flow in the side branches is minimal either at baseline and under combined systemic and coronary vasodilation. Clinically significant flow steal from the coronary circulation to the internal thoracic artery side branches seems then unlikely.

The role of antithrombin III in the perioperative management of the patient with unstable angina.

BACKGROUND: To evaluate the effectiveness of intraoperative administration of antithrombin III (AT III) to improve anticoagulation and preserve the hemostatic mechanisms during cardiopulmonary bypass (CPB) in patients with unstable angina under heparin treatment. METHODS: We divided 22 patients, scheduled for coronary artery bypass grafting, into two groups. Group A (11 patients) received 3000 International Units (IU) of AT III concentrates plus heparin before aortic cannulation. Group B (11 patients) received only heparin. Blood drainage, allogeneic blood transfusions, and intraoperative activated coagulation time were recorded. Also, AT III, thrombin-antithrombin complex (TAT), fragment 1.2 (F 1.2), and D-dimers were measured during the operation and the first postoperative day. RESULTS: Group A patients had fewer transfusions and had less chest-tube drainage. In group A, AT III levels increased after AT III concentrates administration and were always higher than in group B. In group B, F 1.2 and TAT increased significantly more after CPB and at the end of operation. Differences in D-dimers between the groups were not significant. CONCLUSIONS: Intraoperative administration of AT III concentrates allowed adequate anticoagulation during CPB and attenuated the coagulative cascade activation and the consequent consumptive coagulopathy.

Time dependence of endothelium-mediated vasodilation by intermittent antegrade warm blood cardioplegia.

BACKGROUND: The technique of intermittent antegrade warm blood cardioplegia (IAWBC) exposes the heart to brief periods of normothermic ischemia. This may impair endothelial function in coronary arteries. METHODS: Three cardioplegic technique were tested in porcine hearts arrested for 32 to 36 minutes and reperfused for 30 minutes: IAWBC, antegrade cold blood cardioplegia (ACBC), and antegrade cold crystalloid cardioplegia (ACCC). In the hearts arrested with IAWBC, three different intervals of ischemia were used: three 10-minute intervals (IAWBC1), two 15-minute intervals (IAWBC2), and one 30-minute interval (IAWBC3). Rings from the coronary arteries were used to evaluate in vitro the contractile responses to U46619 and the relaxant responses to bradykinin, A23187, and sodium nitroprusside. RESULTS: All six groups (treatment groups and control group) displayed similar responses to U46619 (30 nmol/L) and nitroprusside. In the IAWBC1, IAWBC2, AND ACBC groups, endothelium-dependent relaxations to bradykinin and A23187 were preserved compared with controls, whereas those of the ACCC and IAWBC3 groups were significantly impaired (bradykinin: control, 8.72 +/- 0.07; IAWBC1, 8.73 +/- 0.03; IAWBC2, 8.65 +/- 0.05; IAWBC3, 8.30 +/- 0.07 [p < 0.05]; ACBC, 8.50 +/- 0.03; ACCC, 8.25 +/- 0.09 [p < 0.05]; A23187: control, 7.07 +/- 0.08; IAWBC1, 7.07 +/- 0.06; IAWBC2, 7.04 +/- 0.03; IAWBC3, 6.64 +/- 0.01 [p < 0.05]; ACBC, 6.80 +/- 0.05; ACCC, 6.60 +/- 0.08 [p < 0.05]; nitroprusside: control, 6.19 +/- 0.1; IAWBC1, 6.19 +/- 0.07; IAWBC2, 6.03 +/- 0.03; IAWBC3, 6.08 +/- 0.05; ACBC, 6.04 +/- 0.2; ACCC, 6.05 +/- 0.03; all values are expressed as the negative logarithm of the concentration producing 50% of the maximal response). CONCLUSIONS: Myocardial preservation with IAWBC with ischemic intervals of 15 minutes or shorter does not alter the endothelium-dependent relaxation to bradykinin or A23187 in porcine coronary arteries, but these responses are significantly impaired by ACCC and IAWBC with an ischemic interval of 30 minutes.

A pump-prime aprotinin dose in cardiac surgery: appraisal of its effects on the hemostatic system.

OBJECTIVES: To examine pump-prime aprotinin action on coagulation and fibrinolysis in patients undergoing primary coronary revascularization. DESIGN: A prospective randomized study. SETTING: A university hospital. PARTICIPANTS: Forty-three patients were randomly assigned to either group A, 21 patients treated with 2 x 10(6) kallikrein inhibitor units (KIU) of aprotinin in the cardiopulmonary bypass (CPB) prime, or group B, 22 patients, untreated. INTERVENTIONS: Patients, scheduled for elective coronary surgery, were treated with 2 x 10(6) KIU of aprotinin in the CPB prime. Markers of coagulation and fibrinolysis were evaluated. MEASUREMENTS AND MAIN RESULTS: Surgical times, number of reopenings, and allogeneic blood requirements were collected for each patient. Blood samples were obtained before and after surgery for assessing coagulation (prothrombin time [PT], activated partial thromboplastin time [aPTT], ethanol test, factor VII, antithrombin III [AT III], thrombin-antithrombin III complex [TAT], fragment 1.2 of prothrombin [F1.2]) and fibrinolysis (fibrin degradation products [FOP], plasmin-antiplasmin complexes [PAP], D-dimers) markers variations. In group A surgical times were faster, there were fewer reopenings (0 v 3), and fewer blood transfusions (1 patient v 4 patients). The two groups did not differ for PT, aPTT, and fibrinogen measurements. Postoperative FDP (measurable in more patients of group B at the end of the operation), PAP, and D-dimers postoperatory levels (less increased in aprotinin group) show the antifibrinolytic properties of the drug. Regarding the coagulation markers, factor VII decreased, whereas TAT and F1.2 increased, all to a lesser extent in the aprotinin group compared with the untreated patients, at the end of operation. CONCLUSION: Pump-prime aprotinin minimized, even if not completely inhibited, the activation of coagulation and fibrinolysis during CPB, possibly ensuring a less complicated and safer postoperative recovery. It seemed to allow the maintenance of a correct balance of hemostatic systems, avoiding the risk of thrombotic phenomena.

Arterial-venous PCO2 gradient in early postoperative hours following myocardial revascularization.

OBJECTIVE: To investigate the utility of the arterial-venous PCO2 gradient (P(a-v)CO2) as a marker of the increased risk of postoperative complications in the early postoperative hours following myocardial revascularization. EXPERIMENTAL DESIGN: Prospective study. SETTING: The Postoperative Intensive Care Unit (ICU) of a University Hospital. PATIENTS: Thirty patients (28 males and 2 females; aged 39-70) that consecutively underwent myocardial revascularization. INTERVENTIONS: None. MEASURES: Thirty minutes following arrival at the ICU the hemodynamic parameters were recorder; the arterial and mixed venous hemogasanalyses were obtained; the mixed venous blood hemoglobin saturation (SvO2) and the O2 consumption (VO2) were calculated; and plasma lactate was determined. The arterial and mixed venous hemogasanalyses were determined again 90 minutes after the admission to the ICU. RESULTS: P(a-v)CO2 at 30 minutes was 8.1+/-2.3 mmHg and was only slightly lower at 90 minutes (7.5+/-2.3 mmHg) so that any significant influence of patient transport to the ICU could be ruled out. P(a-v)CO2 did not significantly relate with cardiac index, mixed venous blood O2 saturation, and blood lactate. Twenty-one patients (70%) showed P(a-v)CO2 values higher than 7 mmHg at 30 minutes: in comparison with the others they were characterized by higher arterial blood PCO2 (PACO2) (37+/-5 vs 32+/-3 mmHg; p<0.05) in spite of similar ventilatory variables, by higher mixed venous blood PCO2 (PVCO2) (47+/-6 vs 37+/-3 mmHg; p<0.01), and by lower cardiac index values (2.0+/-0.3 vs 2.3+/-0.6 1/min/m2; p<0.05). The patients that presented abnormally high P(a-v)CO2 values showed a higher rate of postoperative complications, including inadequate cardiac performance, cardiac arrhythmias, prolonged mechanical ventilation, increased plasma creatinine, and jaundice (11 patients out of 21 vs 1 patient out of 9; p<0.05). Finally P(a-v)CO2 was related with arterial-mixed venous O2 content difference (regarded as an index of O2 consumption), hematocrit, blood temperature and PACO2 by multiple linear regression (R=0.74; p<0.01). The coefficients of all factors but hematocrit were significant; hence, apart from the cardiac index, P(a-v)CO2 was influenced by the metabolic rate, the body temperature (possibly because of CO2 release during rewarming), and the impaired CO2 elimination through the lungs. CONCLUSIONS: P(a-v)CO2 represents a useful even if aspecific parameter to monitor patients during the early postoperative period after myocardial revascularization.

[Transcatheter radiofrequency ablation in supraventricular tachycardia in children: immediate results and mid-term follow-up]. / Ablazione transcatetere con radiofrequenza delle tachicardie sopraventricolari in età pediatrica: risultati immediati e di un follow-up a medio termine.

OBJECTIVES: The purpose of this study was to evaluate the efficacy and safety of radiofrequency ablation of supraventricular tachycardias due to a reentry circuit in a group of closely followed-up pediatric patients. PATIENTS: Forty-six pediatric patients (mean age 12.6 years, range 3-18) underwent a total of 48 radiofrequency ablation procedures for reciprocating supraventricular tachycardia. Thirty-nine had an orthodromic reentry tachycardia, 6 an atrioventricular node reentry tachycardia and 1 a permanent junctional reciprocating tachycardia. METHODS: To ablate the overt accessory pathways, the Kent potential (K) was identified and then the shortest A-K, and delta wave-K intervals were measured. The shortest V-A interval was identified for those concealed. For the left-sided accessory pathways, we used the retrograde transaortic approach in 10 procedures and the transseptal approach in 18. Atrioventricular node reentry tachycardia was ablated at the site where the slow-pathway electrogram was recorded. Follow-up clinical data, electrocardiogram, 24-hours Holter monitoring and transesophageal atrial stimulation were obtained and evaluated. RESULTS: Early: We performed a total of 48 procedures. Among 41 procedures performed in the 39 patients with accessory pathway, 38 were successful (92,6%). Mean fluoroscopy time was 31 +/- 18 min. For left sided accessory pathways, mean fluoroscopy time of procedures with retrograde approach was 45 +/- 10 min and with transseptal 23 +/- 12 min (p < 0.01). Ablation of slow-pathway in patients with intranodal reentry tachycardia was successful in 3/6 cases (50%). The patient with permanent junctional reciprocating tachycardia was successfully ablated. Late: All patients are alive and none was lost during the follow-up after a mean time of 12.9 months (range 5-33). Success at last follow-up was 100% in patients with an accessory pathway and 33% in patients with atrioventricular node reentry. In patient with permanent junctional reciprocating tachycardia, the arrhythmia appeared again one month after the procedure, thus a second successful attempt was performed. COMPLICATIONS: Major complications (6,5%) including a right femoral vein thrombosis (one patient), an hematoma without pulse loss (one patient) and a non-sustained monomorphic ventricular tachycardia (one patient). CONCLUSIONS: Our data show high efficacy of radiofrequency ablation in pediatric patients with accessory pathways. The risks are low at follow-up evaluation, but might be helpful a longer-term follow-up in order to evaluate the risk of a long fluoroscopy time and the arrhythmogenic effect of the scar.

Haemodynamic and metabolic effects of surface rewarming after coronary revascularization.

Cardiac surgery is often associated with a postoperative increase in the patient's metabolic rate; surface rewarming has been suggested to decrease the energy expenditure by preventing hypothermia. Thirty patients, undergoing coronary revascularization, were randomly divided into two groups; after surgery group A was rewarmed by a new device that acts by both conduction and convection, while group B was just covered with cotton blankets. Blood, oesophagus and skin (thigh and foot) temperatures were recorded on admission to the intensive care unit (ICU) and 30, 60, 90, 180, 270, and 450 min later. Haemodynamic parameters, oxygen delivery, calculated oxygen consumption, and plasma lactate concentration were assessed as well. Group A warmed up quicker than group B as far as the skin was concerned while the core temperature was unaffected. Group A was also characterized by lower cardiac indices and oxygen consumption. As the occurrence of a dependence of oxygen consumption on delivery could be reasonably ruled out in warmed patients because blood lactate levels were lower than in the controls, we conclude that surface rewarming might have some positive effect in decreasing metabolic demand after cardiac surgery even if the patient's core temperature is little affected. The inhibition of skin temperature receptors could possibly explain this finding.

Rush desensitization in heparin hypersensitivity: a case report.

Among all the known drug intolerances, adverse reactions to heparin are not very common. No desensitization in patients with heparin hypersensitivity has ever been attempted. We report the case of a 55-year-old female patient with mitral stenosis and insufficiency, and tricuspid and aortic insufficiency. The patient underwent heparin treatment, and urticaria occurred with either s.c. calcium heparin or i.v. sodium heparin. Allergy testing (skin tests and patch tests) was negative. A pseudoallergic intolerance was diagnosed. Mitral valve replacement with the extracorporeal circulation method was necessary; therefore, heparin treatment was administered. A heparin rush desensitization together with antihistamine drugs (4 mg clorpheniramine maleate for 3 d) was started: 50 UI (0.5 mg) s.c. sodium heparin were first administered; within 4 d, 5000 UI (50 mg) sodium heparin was administered i.v. with no side-effects. A full-dosage heparin treatment was then administered and heart surgery was easily performed. During the postsurgical course, i.v. sodium heparin was smoothly replaced with s.c. calcium heparin (25,000 UI s.c. per day) and with oral anticoagulants (sodium warfarin).

Somatomedin-C plasma levels after coronary revascularization.

The decrease of Somatomedin-C (SM-C) plasma levels has been recently proposed as an index of acute malnutrition in critically ill patients. In this study SM-C values were determined before surgery for coronary revascularization, on the 2nd and 5th postoperative day. Twenty-four patients were admitted to the study; most of them (16 cases; 66%) presented with an increase of SM-C levels after surgery unlike 8 patients who showed unchanged or decreased levels. Multivariated analysis was applied to the factors that may affect SM-C values. SM-C significantly related to the Modified Predictive Nutritional Index, which was calculated prior to surgery, while no significant relationship was observed with patient age and type of oxygenator. No sign of liver damage was observed, so we concluded that decreased and, perhaps, unchanged SM-C levels after coronary revascularization were probably caused by acute nutritional deficiency. The incidence of this finding was remarkably high (33%) in spite of the absence of apparent malnutrition before surgery.