Vitamins D3 and K2 may partially counterbalance the detrimental effects of pentosidine in ex vivo human osteoblasts.

Osteoporosis is a metabolic multifaceted disorder, characterized by insufficient bone strength. It has been recently shown that advanced glycation end products (AGEs) play a role in senile osteoporosis, through bone cell impairment and altered biomechanical properties. Pentosidine (PENT), a wellcharacterized AGE, is also considered a biomarker of bone fracture. Adequate responses to various hormones, such as 1,25-dihydroxyvitamin D3, are prerequisites for optimal osteoblasts functioning. Vitamin K2 is known to enhance in vitro and in vitro vitamin D-induced bone formation. The aim of the study was to assess the effects of Vitamins D3 and K2 and PENT on in vitro osteoblast activity, to convey a possible translational clinical message. Ex vivo human osteoblasts cultured, for 3 weeks, with vitamin D3 and vitamin K2 were exposed to PENT, a well-known advanced glycoxidation end product for the last 72 hours. Experiments with PENT alone were also carried out. Gene expression of specific markers of bone osteoblast maturation [alkaline phosphatase, ALP; collagen I, COL Iα1; and osteocalcin (bone-Gla-protein) BGP] was measured, together with the receptor activator of nuclear factor kappa-B ligand/osteoproteregin (RANKL/OPG) ratio to assess bone remodeling. Expression of RAGE, a well-characterized receptor of AGEs, was also assessed. PENT+vitamins slightly inhibited ALP secretion while not affecting gene expression, indicating hampered osteoblast functional activity. PENT+vitamins up-regulated collagen gene expression, while protein secretion was unchanged. Intracellular collagen levels were partially decreased, and a significant reduction in BGP gene expression and intracellular protein concentration were both reported after PENT exposure. The RANKL/OPG ratio was increased, favouring bone reabsorption. RAGE gene expression significantly decreased. These results were confirmed by a lower mineralization rate. We provided in vitro evidence that glycoxidation might interfere with the maturation of osteoblasts, leading to morphological modifications, cellular malfunctioning, and inhibition of the calcification process. However, these processes may be all partially counterbalanced by vitamins D3 and K2. Therefore, detrimental AGE accumulation in bone might be attenuated and/or reversed by the presence or supplementation of vitamins D3 and K2.

Long-term outcome after acute type A aortic dissection: does an age limit still exist?

AIM: Aim of the study was to analyze outcome in patients who underwent surgery following type A aortic dissections and to evaluate the long-term survival rates in patients 70 years of age and older and those under 70 years of age, and in males as compared to females. METHODS: Between September 1997 and October 2008, 154 patients were retrospectively enrolled. There were 102 males (66.2%) and 52 females (33.8%) with a mean age of 63.5±12; seven patients (4.5%) were over 80 years of age, 46 (29.8%) were between 70 and 80 years of age and 101 were under 70 years of age at the time of surgery. We compared patients 70 years of age and older with those under 70 years of age, analyzing the early and long-term survival results and postoperative complications. RESULTS: Overall in-hospital mortality was 17.5% and permanent neurological dysfunction occurred in 10 patients (6.5%). Twenty patients (12.9%) died during follow-up. Among the males, the long-term survival rate was 80%, 68% and 51% at 1, 5 and 10 years, respectively. Among the females, survival rate was 84.6%, 72.3% and 47.5% at 1, 5 and 10 years, respectively. Five- and 10-year survival rates were 78.1% and 59.4%, respectively, for patients under 70 years of age, and 50.8% at 5 years and 26.1% at 10 years for those over 70. CONCLUSION: Patients might not be excluded from surgical intervention for acute type A aortic dissection (ATAAD) only due to age. It is important to consider biological age and the clinical features of the patients at the time of surgery. Age is a relative but not absolute contraindication for surgery in ATAAD. Long-term survival was not statistically different between males and females.

The International E-vita Open Registry: data sets of 274 patients.

AIM: After the introduction of the hybrid stent-graft "E-vita-open" by the Essen group in 1/2005 for one stage repair of complex thoracic aortic disease, the International E-vita open Registry was founded in 2008 to study the principles of this treatment algorithm and to control reported favorable single center results on a large patient data set basis up to six years after the first clinical implant. METHODS: Retrospective data work-up after prospective data acquisition was achieved by institution of the International E-vita open Registry with anonymous registration and calculation at Essen University Hospital. From January 2005 to December 2010, 274 patients (mean age 60; 74% males) with complex aortic disease, 190 with aortic dissection (88 acute (AAD), 102 chronic aortic dissection (CAD), and 84 with complex thoracic aortic aneurysm (TAA) were included in the studied. RESULTS: Eighty-one out of 274 (30%) patients underwent emergency surgery. Stent-graft deployment and arch replacement (238 total, 36 subtotal) was performed under selective antegrade cerebral perfusion (75 min mean). Cardiopulmonary bypass (CPB) and cardiac arrest times were mean 235 and 134 minutes, respectively. In-hospital mortality was 15% (40/274), 18% for AAD, 13% for CAD, and 14% for TAA. New strokes were observed in 6% (16/274), spinal cord injury in 8% (22/274). The false lumen (FL) was evaluated throughout the first hospital stay and at a median follow up time of 59 months after surgery. From the first follow up CT-examination to the last, thoracic complete FL thrombosis increased from 83% to 93% in AAD, from 72% to 92% in CAD. Full exclusion of the aneurysmal disease was achieved in 77% (61/79) during the primary hospital stay. CONCLUSION: Favorable single center results could be confirmed by an International community of cardiac surgical centers in regard to hospital mortality and morbidity, as well as a low postoperative complication rate and exclusion of false lumen in aortic dissection.

Complex repair of the thoracic aorta with the E-vita open prosthesis.

AIM: The treatment of complex aortic pathologies of the thoracic aorta remains a challenging issue in aortic surgery. The'' Frozen elephant trunk'' technique represents a recent development of the classic elephant trunk technique combining endovascular with conventional surgery. METHODS: Between January 2007 and January 2008, 24 patients were operated on for complex pathologies of the thoracic aorta using the frozen elephant trunk technique with the E-vita open prosthesis. There were 21 male (87.5%) and the mean age was 62.4+/-9.9 years. The majority of patients (N=11) presented type A chronic dissection, 6 (25%) patients had chronic aneurysm of distal aortic arch and 5 (20.8%) type B aortic dissection associated with ascending aorta/aortic arch aneurysm. There were 2 cases of acute aortic dissection (1 type A and 1 type B). Nine patients (37.5%) underwent previous cardiovascular operations. RESULTS: The overall in-hospital mortality was 4.2% (1 patient). None patient developed postoperative stroke and 1 patient suffered from spinal cord ischemia (1 paraparesis, 1 paraplegia). There were 2 cases (8.3%) of renal failure (dialysis), 2 patients (8.3%) had pulmonary complications and 2 patients (8.3%) needed rethoracotomy for bleeding. Five patients (21.7%) required extension of the descending thoracic aorta repair with endovascular treatment for persistent perfusion of dilated false lumen. CONCLUSION: The Frozen Elephant trunk technique with the new E-vita open prosthesis combines surgical and interventional technologies and it represents a feasible and efficient option in the treatment of complex aortic pathologies. However long term follow up is required.

Persistence of Candida albicans candidemia in non-neutropenic surgical patients: management of a representative patient in the absence of second-line treatment guidelines.

Primary treatment failure and mortality in non-neutropenic patients with candidemia is high according to clinical trial experience. Current guidelines are mainly useful only for first line treatment strategies.We describe treatment failure and persistent protracted Candida albicans candidemia without clinically evident ocular involvement nor catheter recolonization in a malnourished non-neutropenic surgical patient with peritonitis. Primary antifungal treatment failure with fluconazole and secondary treatment failure with caspofungin occurred in the absence of evident Candida seeding the eye, valvular endocardium, or the intravascular catheter. Switch to liposomal amphotericin B was followed by clinical and microbiological cure. In patients with multiple risk factors for the acquisition of candidemia and life-threatening clinical conditions, the possibility of primary/secondary failure of new potent antifungal regimens may be initially neglected. Additional multicenter controlled clinical data are needed to guide the timing and choice of secondary antifungal treatment regimens in non-neutropenic candidemia patients.

Nine years experience of aortic arch repair with the aid of antegrade selective cerebral perfusion.

AIM: Antegrade selective cerebral perfusion (ASCP) is gaining widespread popularity in aortic arch surgery because it has been demonstrated to be an optimal technique of cerebral protection. This study demonstrates the clinical results of aortic arch repair with ASCP. METHODS: Between November 1996 and September 2004, 250 patients underwent thoracic aorta replacement using ASCP under moderate hypothermia. Mean patients age was 63+/-11.5 years. Presenting pathologies were chronic aneurysm in 136 patient (54.4%), type A acute aortic dissection in 80 patients (32%), post-dissection aneurysm in 30 patients (12%). Ascending aorta and hemiarch replacement was performed in 63 patients (25.2%), ascending aorta and total arch replacement in 131 patients (52.4%), total arch replacement in 33 patients (13.2%), total arch and descending aorta replacement in 10 patients (4%) and complete replacement of the thoracic aorta in 13 patients (5.2%). RESULTS: Hospital mortality was 11.6%. Multivariate analysis showed preoperative renal failure (P=0.050), cerebral perfusion time (P<0.001), pulmonary complications (P=0.009) and postoperative dialysis (P=0.030) as risk factors for hospital mortality. Permanent neurologic deficits occurred in 4 patients (1.6%) and coronary artery disease (P=0.029) was found to be the only independent risk factor. Transient neurologic deficits were noted in 18 patients (7.2%). Multivariate analysis revealed age (P=0.043), coronary artery disease (P=0.036), urgent/emergency status of the operation (P=0.016) and concomitant aortic valve replacement (P=0.001) to be independent predictors of transient neurologic dysfunction. The actuarial survival rate at 7 years was 61.7%. CONCLUSIONS: | Our results confirmed that ASCP is a safe method of brain protection allowing complex aortic repairs to be performed with good results in terms of hospital mortality and neurologic outcome. Cerebral perfusion time did not influence postoperative outcome. The use of moderate hypothermia avoided all undesirable effects of deep hypothermia.

Reoperations on the ascending aorta and aortic root. Early and late results?

AIM: We have retrospectively evaluated our results after aortic root and ascending aorta reoperations to determine risk factors of early death and late mortality. METHODS: From January 1986 to April 2002, 73 patients underwent ''reoperative'' procedures on the aortic root and the ascending aorta. The mean age was 56.1+/-13.4 years and males numbered 62 (84.9%). The most frequent indication for reoperation was degenerative aortic aneurysm (49.3%) followed by post-dissection aneurysm (11%). Aortic root replacement with composite valve graft was performed in 47 patients (64.4%) and with aortic homograft in 2 (2.7%). Nineteen patients (26%) underwent ascending aorta replacement with tubular graft, and 4 (5.5%) underwent tailoring aortoplasty of the ascending aorta. RESULTS: The 30-day mortality rate was 16.4% (12 patients). Mortality following elective operations was 8%, and that following urgent or emergency operations was 34.8% (p=0.002). Late survival of hospital survivors at 1, 5 and 10 years was 93.8%, 77.7% and 37%, respectively. In the multivariate Cox regression analysis chronic renal failure (p=0.003) and urgent or emergency operation (p=0.018) were found to be independent predictors of late mortality. CONCLUSIONS: Reoperations on the ascending aorta can be accomplished with acceptable early mortality and satisfactory long-term RESULTS: More radical treatment of the aortic pathology at the initial operation may reduce the need for further reoperations. A careful follow-up is extremely important for detecting complications of the first operation or progression of the aortic pathology before an emergency operation, predictive of poorer early and late outcome, is needed.

Myocardial protection using HTK solution in minimally invasive mitral valve surgery.

BACKGROUND: Minimally invasive cardiac surgery (MICS) is a safe and satisfactory approach used mainly in mitral valve surgery with excellent results in many centers. Cardioplegia administration can be still a problem, especially when an endoaortic clamp is used. We retrospectively analyzed our early results with histidine-triptophane-ketoglutarate (HTK) solution used for myocardial protection in MICS. METHODS: Between February 2003 and February 2004, 8 patients underwent mitral valve surgery using an endo- cardiopulmonary bypass (CPB) system and HTK solution as myocardial protection. The mean patient age was 67.7 +/- 9.2 years, and the preoperative ejection fraction was normal in all patients. Three patients had valve repair and 5 had valve replacement. Mean CPB time was 129.2 +/- 19.4 minutes, and aortic cross-clamp duration was 88.5 +/- 15.4 minutes. RESULTS: In every case HTK solution was used for only a single dose for cardioplegia at the beginning of the procedure, without any recalls. The heart restarted spontaneously at reperfusion in 6 of 8 cases (75%), and there were no significant modifications in electrocardiogram results or myocardial cytonecrosis enzymes (creatine kinase and its MB fraction) during the postoperative period. CONCLUSIONS: HTK solution is a cold crystalloid cardioplegia solution that has demonstrated its utility in MICS because it provides a safe long cardioplegic arrest time and it reduces the risk of inadequate coronary perfusion due to dislodgement of the endoaortic clamp.

Amyloid deposition as a cause of atrial remodelling in persistent valvular atrial fibrillation.

AIM: The spectrum of histological alterations, namely atrial amyloidosis, in the right and left atria of patients with chronic persistent atrial fibrillation (AF) and rheumatic heart disease is not completely known. METHODS AND RESULTS: One hundred and twenty-eight atrial appendages (66 left and 62 right), obtained from 72 patients with rheumatic valve disease and chronic AF undergoing cardiac surgery for valve replacement or repair and AF treatment were histologically evaluated for the presence of amyloid deposits. One hundred and four specimens of left and right auricles from 52 patients in sinus rhythm with severe chronic heart failure undergoing heart transplant were also analyzed (controls). Amyloid was found in 33 (46%) valvular patients with chronic persistent AF and in 6 (12%) controls. Amyloid was related to the presence and duration of AF, was more frequently found in left atrial samples and was independent of age. On stepwise logistic regression analysis, AF duration and female gender were independently related to amyloid deposition. CONCLUSIONS: Patients with long-standing AF and rheumatic heart disease have a very high prevalence of atrial amyloidosis. Amyloid deposition is more frequent in left than in right atrial appendage and correlates with AF duration and female gender. Amyloid deposition could constitute an additional histological feature in the structural remodeling of atria during long-standing AF, at least in rheumatic valve disease. Persistence of AF might play a pivotal role in promoting amyloid deposition.

Surgery using median sternotomy for diffuse aneurysmal disease of the thoracic aorta.

We present our experience using an anterior approach for the replacement of an extensive aneurysm of the thoracic aorta. In recent years we have performed surgery on 20 patients by means of a median sternotomy for aneurysms of the ascending aorta, aortic arch, or descending thoracic aorta. In all but 1 of the patients, a procedure in the ascending aorta was also performed. In some patients a small anterior left thoracotomy at the 4th intercostal space was required to allow the replacement of the aorta as for the diaphragm. Antegrade selective cerebral perfusion (ASCP) according to Kazui's technique was used as a brain protection method. All procedures were performed successfully and the aneurysm was completely resected. No neurologic complications or other major complications occurred. We believe that the anterior approach for extensive thoracic aorta replacement is feasible, allows the use of ASCP, and has shown encouraging results.

Successful allogeneic hematopoietic stem cell transplantation (HSCT) for Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder characterized by pancreatic insufficiency, short stature, skeletal abnormalities and bone marrow dysfunction. Patients with SDS have varying degrees of marrow aplasia, which can be severe or progress to leukemic transformation. While allogeneic hematopoietic stem cell transplantation (HSCT) can be curative for the hematologic disturbances of SDS, a recent review of the literature reveals few survivors. Poor outcome with HSCT is often related to excessive cardiac and other organ toxicity from transplant preparative therapy. We describe two young children with SDS who developed aplastic anemia and subsequently underwent successful allografting using a non-cardiotoxic conditioning regimen. Case 1 received marrow from an HLA-identical sibling while case 2 received partially matched umbilical cord blood from an unrelated donor. Both patients are presently alive and well with sustained donor engraftment and excellent hematopoietic function at 36 and 22 months post-HSCT.

Antegrade selective cerebral perfusion during surgery of the thoracic aorta: risk analysis.

OBJECTIVE: To determine independent predictors of neurologic outcome and hospital mortality after surgery of the thoracic aorta using moderate hypothermic circulatory arrest and antegrade selective cerebral perfusion. METHODS: Between November 1996 and June 2000, 96 consecutive patients (69 men, 27 women; mean age 63+/-10 years) underwent operations on the thoracic aorta with the aid of moderate hypothermic circulatory arrest and antegrade selective cerebral perfusion. Sixty-four patients were operated on electively (66.7%), 32 emergently (33.3%). Indications for surgery were: type A acute dissection in 30 patients (31.3%), chronic aneurysm in 66 (68.8%). Seventeen patients (17.7%) had undergone previous aortic/cardiac surgical procedures. The mean selective cerebral perfusion time was 52.2+/-31.9 min (range, 18-220 min). Preoperative, intraoperative, and postoperative factors were analyzed by univariate and multivariate analysis to identify predictors of hospital mortality and neurologic outcome. RESULTS: There were no operative deaths; the hospital mortality rate was 11.5% (11/96). Stepwise logistic regression revealed preoperative renal dysfunction (P=0.021), type A acute dissection (P=0.053), coronary artery bypass grafting (P=0.058), post-operative pulmonary complications (P=0.000) and repeat thoracotomy for bleeding (P=0.027) as independent predictors of hospital mortality. One patient sustained a permanent neurologic deficit (1%). Transient neurologic deficit occurred in eight patients (8.3%). Coronary artery bypass grafting (P=0.013), and postoperative cardiac complications (P=0.049) were statistically associated with an increased risk of any (transient and permanent) neurologic dysfunction on univariate analysis. Stepwise logistic regression indicated coronary artery bypass grafting as independent factor for any neurologic dysfunction. CONCLUSION: This study confirmed that selective cerebral perfusion is an effective method of cerebral protection allowing complex thoracic aorta operations to be performed with low risk of hospital mortality and adverse neurologic outcome. We didn't find that the duration of selective cerebral perfusion time influence hospital mortality and any neurologic deficit.

Antegrade selective cerebral perfusion during operations on the thoracic aorta: our experience.

BACKGROUND: Various methods of cerebral protection have been used during aortic arch operations. Deep hypothermia with circulatory arrest is the most common technique but has a limited safe period for circulatory arrest. Selective cerebral perfusion has been introduced to prolong this safe period. We reviewed our experience with antegrade selective cerebral perfusion during surgical repair of the thoracic aorta. METHODS: Between November 1996 and December 1998, 57 consecutive patients were operated on for aortic arch aneurysms using selective cerebral perfusion. Forty-one were men (71.9%), and 16 were women. The mean age was 63.2 years. Thirty-seven patients had chronic aneurysms, and 20 had type A acute dissection. Preoperative, intraoperative, and postoperative factors were analyzed by univariate and multivariate analysis to identify predictors of early mortality and transient neurologic dysfunction. RESULTS: There were no permanent neurologic deficits. The early mortality rate was 8.8% (5 patients). Multivariate analysis revealed preoperative renal failure (p = 0.0338) and repeat thoracotomy for bleeding (p = 0.0201) to be independent risk factors for early mortality. The factor postoperative cardiac complications (p = 0.0368) was the only independent predictor of transient neurologic dysfunction, and it occurred in 3 patients (5.3%). CONCLUSIONS: The present study confirmed that preoperative renal failure and repeat thoracotomy for bleeding are significant predictors of mortality in aortic arch operations using selective cerebral perfusion and that cerebral perfusion time has no influence on the postoperative outcome. We believe that selective cerebral perfusion is an optimal technique of cerebral protection during operations on the aortic arch.

Spontaneous dissection of coronary artery in a patient with ascending aortic aneurysm and aortic valve regurgitation.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction associated with a significant high morbidity and mortality. It usually occurs in relatively young patients and it is frequently found at autopsy. We report a case of a 42-year-old woman, who underwent resection of subaortic diaphragm ten years earlier presenting with postero-lateral myocardial infarction. Coronary arteriography revealed a dissection of the left main stem extending distally to the left anterior descending artery (LAD) and circumflex artery (Cx); occlusion of the postero-lateral branch of the Cx; severe aortic valve regurgitation and ascending aortic aneurysm. She was successfully operated on in emergency and underwent myocardial revascularization and separate replacement of the aortic valve and the ascending aorta. In this specific case of coronary dissection and severe aortic regurgitation it is mandatory to perform surgery in emergency to limit infarction evolution and avert loss of life.

Ranitidine bismuth citrate with either clarithromycin 1 g/day or 1.5 g/day is equally effective in the eradication of H. pylori and healing of duodenal ulcer.

BACKGROUND: No randomized double-blind studies have been performed to compare clarithromycin 1 g/day with higher doses of the macrolide (1.5 g/day) when combined with ranitidine bismuth citrate (RBC). AIM: To compare H. pylori eradication and ulcer healing rates of RBC 400 mg b.d. for 4 weeks combined for the first 2 weeks either with clarithromycin 500 mg b.d. (Group A) or clarithromycin 500 mg t.d.s. (Group B). METHODS: Two hundred and seventy-three patients with H. pylori-positive active duodenal ulcer were included. H. pylori infection was detected by CLO-test and histology on antral and corpus biopsies before and at least 4 weeks after the end of therapy. Eradication was assumed if both CLO-test and histology results were negative for H. pylori. RESULTS: Eradication/healing rates according to intention-to-treat and per protocol analysis were 76/82% and 87/92% for Group A and 78/85% and 88/95% for Group B, respectively (P = N.S.). Adverse events were reported by 7% and 12% of patients in Groups A and B, respectively, and they were generally mild. CONCLUSIONS: RBC in co-prescription with clarithromycin 500 mg b.d. is as effective as RBC plus clarithromycin 500 t.d.s. in eradicating H. pylori and healing duodenal ulcers.

Cardiac papillary fibroelastoma of the mitral valve chordae.

Papillary fibroelastomas are rare, benign, primary cardiac tumors, usually single and small. The neoplasm consists of a leafy, soft excrescence typically located on the cardiac valves. Although papillary fibroelastomas are usually an asymptomatic incidental finding at autopsy, or during cardiac operation, they are occasionally associated with embolic coronary or cerebral symptoms. A case of a patient is reported with papillary fibroelastoma of the mitral valve chordae, who presented several transitory ischemic attacks characterized by loss of conscience, visual bilateral deficit and right emiparesis. Because of their potential systemic embolization, we believe that these lesions should be always excised.

Surgical indications and timing of repair of traumatic ruptures of the thoracic aorta.

BACKGROUND: The outcome of patients with acute traumatic rupture of the thoracic aorta after motor vehicle accidents is strongly conditioned by injuries to other districts. The timing of repair is controversial when the patients arrive alive to the hospital. METHODS: A series of 42 patients with acute traumatic rupture of the thoracic aorta observed between January 1980 and June 1996 was divided into two groups: group I underwent immediate repair (21 patients) and in group II operation was performed after intensive medical treatment and management of the associated lesions and monitoring of the aortic tear. RESULTS: The mortality in group I patients was 19% and the morbidity was more significant than in group II where no deaths were reported and complications were minor. CONCLUSIONS: Patients with acute traumatic rupture of the thoracic aorta may have a better fighting chance if aortic operation is postponed to the most favorable moment after undergoing life-sustaining measures and management of the major associated lesions. Needless to say, evolution should be closely monitored by computed tomographic scans and magnetic resonance imaging.

Damage to the circumflex coronary artery during mitral valve repair with sliding leaflet technique.

We report a case of damage to the circumflex coronary artery during mitral valve repair using sliding leaflet technique in a patient with a posterior mitral leaflet prolapse and coronary artery disease who underwent mitral valve reconstruction using Carpentier's technique and coronary artery bypass grafting. This case underscores the risk of circumflex coronary artery injury during mitral valve reconstruction, especially in patients with left coronary dominance or codominance, and therefore emphasizes the importance of knowing the coronary artery anatomy preoperatively. The use of intraoperative transesophageal echocardiography is mandatory for the evaluation of mitral valvuloplasty.