Development of an Innovative Berberine Food-Grade Formulation with an Ameliorated Absorption: In Vitro Evidence Confirmed by Healthy Human Volunteers Pharmacokinetic Study.

OBJECTIVE: To evaluate in vitro solubility, bioaccessibility, and cytotoxic profile, together with a pharmacokinetic profile by oral administration to healthy volunteers of a novel food-grade berberine formulation (BBR-PP, i.e., berberine Phytosome®). RESULTS: An in vitro increase of solubility in simulated gastric and intestinal fluids and an improved bioaccessibility at intestinal level along with a lower cytotoxicity with respect to berberine were observed with BBR-PP. The pharmacokinetic profile of the oral administration to healthy volunteers confirmed that berberine Phytosome® significantly ameliorated berberine absorption, in comparison to unformulated berberine, without any observed side effects. The berberine plasma concentrations observed with both doses of BBR-PP were significantly higher than those seen after unformulated berberine administration, starting from 45 min (free berberine) and 30 min (total berberine). Furthermore, BBR-PP improved berberine bioavailability (AUC) was significantly higher, around 10 times on molar basis and with observed dose linearity, compared to the unformulated berberine. CONCLUSION: These findings open new perspectives on the use of this healthy berberine formulation in metabolic discomforts.

St. Jude Medical Trifecta aortic valve: results from a prospective regional multicentre registry.

BACKGROUND: The Trifecta aortic bioprosthesis (St. Jude Medical, Inc., St. Paul, MN, USA) is a stented pericardial heart valve with excellent preliminary results. Aim of the study was to evaluate its early clinical and hemodynamic performances in a multicenter regional registry. METHODS: Between January 2011 and June 2012, 178 consecutive patients undergoing aortic valve replacement with the Trifecta bioprosthesis were prospectively enrolled at 9 Italian centers. Clinical and echocardiographic data were collectedat discharge, 6-months and at 1-year postoperatively. RESULTS: The average age was 75.4 ± 7.7 years,and 95 (53 %) were men. Indication for valve replacement included stenosis in 123 patients (69 %), mixed lesions in 25 (14 %), and regurgitation in 30 (17 %). Ninety-three (52 %) patients were in NYHA functional class III/ IV. Hospital mortality accounted for 5 (2.8 %) patients. No valve-related perioperative complications were encountered. Median follow-up was 20.5 months (range: 1-34). Early (≤6 months) complications included one thromboembolic event, one major bleeding, and 3 endocarditis (2 explants). Two late (>6 months) thromboembolic events and two endocarditis (1 explant) were registered. No valve thrombosis or structural deterioration were observed after discharge. At 30-months, freedom from all-cause mortality was 87 %, freedom from valve-related mortality 99.4 %, freedom from endocarditis 97.5 %, and freedom from valve explants 98 %. At 1-year, mean gradients ranged from 8 to 16 mmHg, and effective orifice area indexes from 1.0 to 1.2 cm(2)/m(2) for valve sizes from 19 to 27 mm, respectively. No patients had severe prosthesis-patient mismatch. CONCLUSIONS: Trifecta bioprosthesis provided favourable clinical and hemodynamic results over time.

Systemic and myocardial inflammatory response in coronary artery bypass graft surgery with miniaturized extracorporeal circulation: differences with a standard circuit and off-pump technique in a randomized clinical trial.

Inflammatory response and hemodilution are the main drawbacks of extracorporeal circulation. We hypothesize that the use of miniaturized extracorporeal circulation (MECC) might lower the systemic and myocardial inflammatory patterns compared with a standard system (SECC) and off-pump coronary artery bypass grafting (OPCABG). Sixty-one patients undergoing isolated coronary artery bypass graft were prospectively randomized to MECC (n = 19), SECC (n = 20), or OPCABG (n = 22). Blood samples were collected from radial artery and coronary sinus to analyze blood lactate, hemodilution, and markers for inflammation and endothelial activation such as tumor necrosis factor (TNF)-α, interleukin-6, monocyte chemotactic protein-1, and E-selectin. No differences were observed in early clinical outcome. Interleukin -6 levels increased in every group during and after cardiac surgery, whereas TNF-α values grew in the SECC group (p = 0.05). E-selectin systemic values decreased during and after operation (p = 0.001) in every group. Monocyte chemotactic protein-1 systemic and cardiac levels raised only in SECC group (p = 0.014). In conclusion, MECC is comparable to SECC and OPCABG in the clinical outcome of low-risk patients, and it might be extensively used with no additional intraoperative risk. The analysis of the inflammatory patterns of endothelial activation shows MECC as effective as OPCABG, suggesting further studies to clarify MECC recommendation in high-risk patients.

Myocardial revascularization with miniaturized extracorporeal circulation versus off pump: Evaluation of systemic and myocardial inflammatory response in a prospective randomized study.

OBJECTIVE: This prospective randomized study sought to verify the systemic inflammatory response, inflammatory myocardial damage, and early clinical outcome in coronary surgery with the miniaturized extracorporeal circulation system or on the beating heart. METHODS: Sixty consecutive patients were randomized to miniaturized extracorporeal circulation (n = 30) or off-pump coronary revascularization (off-pump coronary artery bypass grafting, n = 30). Intraoperative and postoperative data were recorded. Plasma levels of interleukin-6 and tumor necrosis factor-alpha were measured from systemic blood intraoperatively, at the end of operation, and 24 and 48 hours thereafter. Levels of the same markers and blood lactate were measured from coronary sinus blood intraoperatively to evaluate myocardial inflammation. Markers of myocardial damage were also analyzed. RESULTS: One patient died in the off-pump coronary artery bypass grafting group. There was no statistical difference in early clinical outcome in both groups. Release of interleukin-6 was higher in the off-pump coronary artery bypass grafting group 24 hours after the operation (P = .03), whereas levels of tumor necrosis factor-alpha were not different in both groups. Cardiac release of interleukin-6, tumor necrosis factor-alpha, and blood lactate were not different in both groups. Release of troponin T was not significantly different in both groups. Levels of creatine kinase mass were statistically higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group, but only at the end of the operation (P < .0001). Hemoglobin levels were significantly higher in the miniaturized extracorporeal circulation group than in the off-pump coronary artery bypass grafting group after 24 hours (P = .01). CONCLUSION: Miniaturized extracorporeal circulation can be considered similar to off-pump surgery in terms of systemic inflammatory response, myocardial inflammation and damage, and early outcome.

Results, side effects and complications after thoracoscopic sympathetic block by clamping. The monza clinical experience.

BACKGROUND: Video-endoscopic sympathectomy is the current treatment of choice for severe primary hyperhidrosis. Because of the possible postsurgical side effects, the procedure is carried out using removable endoclips that block sympathetic nerve transmission. This study describes the short and "midterm" side effects and complications of this method for the treatment of palmar, axillary, and facial hyperhidrosis. MATERIALS AND METHODS: Two hundred and ninety-four sympathectomies were carried out between September 2003 and June 2006 and followed-up after 17 months. Patients with isolated facial hyperhidrosis were clamped at the T2-3 level clamping. Patients with isolated axillary hyperhidrosis were clamped at the T3-4 level. RESULTS: All patients with palmar and palmar-axillary hyperhidrosis were completely satisfied after clamping at the third thoracic ganglion (T3) level. Immediate complete recovery was achieved in 98% of patients postsurgery. Major complications were Horner's syndrome (1%) and pneumothorax (3%). Compensatory sweating occurred in 22%. No cases of gustatory sweating were reported. All patients were "satisfied" with their results and no patients requested removal of the clips. INTERPRETATION: Thoracoscopic sympathecotomy clamping is a successful treatment for hyperhidrosis. Local hyperhydrosis does not reoccur after 17 months, but there is some degree of compensatory hyperhidrosis.

Symptomatic right atrial appendance aneurysm: diagnosis and resection.

Idiopathic right atrial enlargement is a rare cardiac anomaly presenting as a giant right atrium. A 20-year-old woman presenting for pneumothorax was found to have a pericardial mass compressing right ventricle. Echocardiography and magnetic resonance suggested the diagnosis of lone right atrial appendance enlargement. The mass was surgically removed and histopathology confirmed the diagnosis of right atrial appendance aneurysm. The case is notable for its rarity.

Video-assisted thoracic surgical resection of giant cardiac lipoma: a case report.

We describe the case of a 73-year-old man, with a history of previous coronary artery by-pass, who presented at our division for new onset of angina, hypotension and dyspnea due to a primary giant para-cardiac lipoma. The success of complete resection of the mass achieved by means of video-assisted thoracic surgical procedure demonstrated the efficacy and safeness of this method in the treatment of benign cardiac tumours.

Mitral valve annuloplasty with a semirigid annuloplasty band in ischemic mitral regurgitation: early results.

OBJECTIVE: A trigone-to-trigone semirigid annuloplasty band (C-G Future Band, Medtronic, Inc., Minneapolis, Minnesota, USA) was introduced in 2001 for mitral valve repair. We report our early clinical and echocardiographic results with this new device to correct ischemic mitral regurgitation. METHODS: Between January 2002 and December 2004, among 216 patients operated on for mitral regurgitation, 107 patients had a C-G Future Band annuloplasty and 85 consecutive patients (72.6% male; mean age 66.9 +/- 8.6 years) received this annuloplasty band to correct ischemic mitral regurgitation. Mean follow-up was 14.3 +/- 9.8 months (range 0.2-37 months). Clinical and echocardiographic assessment was accomplished preoperatively, postoperatively, at 6 and 12 months, and at two years. RESULTS: Perioperative mortality was 3.7% (three in-hospital deaths), whereas overall survival at two years was 88.7 +/- 4.2%. Immediately after repair, echocardiographic mitral regurgitation was dramatically reduced (2.5 +/- 0.6 vs. 0.9 +/- 0.6; P < 0.0001); ejection fraction increased from 43.8 +/- 11% preoperatively to 44.8 +/- 12% postoperatively (P = 0.007). At the time of follow-up, New York Heart Association (NYHA) functional class was significantly improved (mean preoperative NYHA class 2.04 +/- 0.9 vs. mean postoperative NYHA class 1.25 +/- 0.6; P < 0.0001). No patient experienced thromboembolic events and no late mitral valve reoperation occurred. CONCLUSIONS: Early and mid-term mitral valve function is satisfactory with trigone-to-trigone semirigid band annuloplasty, with excellent repair durability immediately after the operation and at two years. Moreover, after annuloplasty repair, an improvement in clinical functional status is obtained. A wider use of this semirigid annuloplasty band can be recommended.

Right gastroepiploic artery graft: long-term clinical follow-up in 271 patients--experience of a single center.

BACKGROUND AND AIM: We present our experience in the use of right gastroepiploic artery (rGEA). Long-term clinical results are reported. METHODS: From April 1994 to June 2005, 271 patients (257 males, mean age 56.2 +/- 7.1) underwent coronary artery bypass grafting with the use of rGEA. Preoperative, perioperative, and postoperative data were retrospectively collected and clinical results and survival were examined. The end points of follow-up were death and recurrence of cardiac events such as angina and myocardial infarction (MI). The mean follow-up was 8.2 +/- 2.9 years. RESULTS: Left ventricular ejection fraction ranged from 0.20 to 0.68 (mean 0.55 +/- 0.7). The mean cardiopulmonary bypass time was 96.8 +/- 15.8 minutes and the mean cross-clamping time was 69.7 +/- 14.2 minutes. The mean number of distal anastomosis was 3.3 +/- 0.7 (range 2 to 5). Early mortality was 2.6% and postoperative MI occurred in three patients. There were 21 (7.9%) late deaths and three of them (1.2%) were cardiac related. Actuarial 10-year-survival of all deaths, including in-hospital death, was 70.8%+/- 9.9%. No abdominal complications occurred during or after rGEA harvesting. Seven patients have been suffering of recurrence of angina. Angiography was performed only on those patients with recurrent angina. CONCLUSION: The rGEA can be considered as a valid arterial conduit, relatively easy to harvest, safe to use with low perioperative risks, and good mid- and long-term results. The low early and late rate mortality and the satisfactory clinical results are good reasons for using routinely this conduit in selected patients.

Effects of papaverine and glycerylnitrate-verapamil solution as topical and intraluminal vasodilators for internal thoracic artery.

BACKGROUND: Arterial spasm is described as an event occurring after left internal thoracic artery (LITA) harvesting. Many vasodilators have been used to treat or prevent LITA spasm. The aim of this study is to compare the effects between glyceril-trinitrate/verapamil (GV) solution and papaverine to treat LITA spasm and to determine the best delivery method. METHODS: One hundred consecutive ischemic patients were randomly assigned to three groups: group GV (n = 34, GV solution), group P (n = 33, papaverine), or group C (n = 33, normal saline). In each patient, pedicled LITA was harvested, thereafter sprayed with the randomized solution, and covered with a sponge. Fifteen minutes after heparin administration, LITA was distally divided; flow per minute was calculated after measuring the free flow for over 15 seconds; this is named "topical free flow." Then, the vasodilator was injected intraluminally and free flow per minute was measured; this is called "intraluminal free flow." RESULTS: Analysis of variance was applied to detect differences among groups; paired-sample t test was used for LITA topical free flow versus intraluminal free flow within single groups. Mean LITA free flows were as follows: group GV, topical free flow = 38.6 +/- 25.2 mL/min versus intraluminal free flow = 58.8 +/- 29 mL/min (p < 0.0001); group P, topical free flow = 45.4 +/- 38.9 mL/min versus intraluminal free flow mL/min (p < 0.0001); group C, topical free flow = 31.6 +/- 19.9 mL/min versus intraluminal free flow = 34 +/- 19.8 mL/min (p = 0.14). Topical free flow difference among the three groups was not statistically significant (p = 0.1); intraluminal free flow difference was statistically significant (p = 0.001). Intraluminal free flow in group GV and in group P were higher than intraluminal free flow in group C (p = 0.004 and 0.001, respectively). Intraluminal free flow of group P was higher than that of group GV; this difference did not reach statistical significance (p = 1.00). CONCLUSIONS: Glyceril-trinitrate/verapamil solution and papaverine are able to treat the spasm and increase the flow of the LITA, when they are used intraluminally. When used topically, these vasodilator agents do not ensure an optimal free flow.

Dual left anterior descending coronary artery from right aortic sinus: report of a case of recurrent unstable angina after CABG.

Anomalies of the left coronary artery are very rare, with an incidence range between .3% and 1.64%. The diagnosis is generally incidental during coronary angiogram, coronary artery bypass operation, or autopsy. However, sometimes this anomaly is not recognized during CABG operation and can be responsible for the recurrence of angina after CABG operation and even compromise the outcome. We presented a case in which the dual left anterior coronary artery from the right aortic sinus occasionally was shown in a coronary angiogram after CABG operation; the angiogram was performed because of the recurrence of angina.

ECMO support for the treatment of cardiogenic shock due to left ventricular free wall rupture.

Left ventricular free wall rupture (LVFWR) is still an uncommon catastrophic complication after acute myocardial infarction (MI), and it is one of the most frequent causes of sudden cardiac death. Immediate surgical repair is the treatment of choice. When LVFWR presents acutely with tamponade and cardiogenic shock in emergency department, salvage with a good outcome is still possible by timely pericardiocentesis and extracorporeal membrane oxygenation (ECMO) support. We report a case of cardiac rupture with tamponade and cardiogenic shock in which cardiopulmonary support with portable ECMO was used to rescue the patient before the operation.