Donor natural killer cells trigger production of ß-2-microglobulin to enhance post-bone marrow transplant immunity.

Allogeneic hematopoietic transplantation is a powerful treatment for hematologic malignancies. Posttransplant immune incompetence exposes patients to disease relapse and infections. We previously demonstrated that donor alloreactive natural killer (NK) cells ablate recipient hematopoietic targets, including leukemia. Here, in murine models, we show that infusion of donor alloreactive NK cells triggers recipient dendritic cells (DCs) to synthesize ß-2-microglobulin (B2M) that elicits the release of c-KIT ligand and interleukin-7 that greatly accelerate posttransplant immune reconstitution. An identical chain of events was reproduced by infusing supernatants of alloreactive NK/DC cocultures. Similarly, human alloreactive NK cells triggered human DCs to synthesize B2M that induced interleukin-7 production by thymic epithelial cells and thereby supported thymocyte cellularity in vitro. Chromatography fractionation of murine and human alloreactive NK/DC coculture supernatants identified a protein with molecular weight and isoelectric point of B2M, and mass spectrometry identified amino acid sequences specific of B2M. Anti-B2M antibody depletion of NK/DC coculture supernatants abrogated their immune-rebuilding effect. B2M knock-out mice were unable to undergo accelerated immune reconstitution, but infusion of (wild-type) NK/DC coculture supernatants restored their ability to undergo accelerated immune reconstitution. Similarly, silencing the B2M gene in human DCs, before coculture with alloreactive NK cells, prevented the increase in thymocyte cellularity in vitro. Finally, human recombinant B2M increased thymocyte cellularity in a thymic epithelial cells/thymocyte culture system. Our studies uncover a novel therapeutic principle for treating posttransplant immune incompetence and suggest that, upon its translation to the clinic, patients may benefit from adoptive transfer of large numbers of cytokine-activated, ex vivo-expanded donor alloreactive NK cells.

Postangioplasty aneurysm of right coronary artery.

BACKGROUND: Coronary artery aneurysms are an uncommon disease whose incidence ranges from 0.3% to 5.3%. The right coronary artery is affected in 40%-70% of cases. Percutaneous coronary angioplasty is among causative factors, in particular with stent implantation. AIMS: We present a case of large postangioplasty aneurysm of the right coronary artery requiring surgical correction. MATERIALS & METHODS: A 70-year-old man with history of multiple coronary angioplasty procedures was admitted with diagnosis of aneurysm of the right coronary artery at the site of past DES insertion. RESULTS: Under cardiopulmonary bypass, the large aneurysm was incised and oversewn with final grafting of the posterior descending artery with in situ right internal mammary artery. The postoperative course was uneventful. DISCUSSION: The treatment options for coronary artery aneurysms range from medical, percutaneous and surgical approaches. CONCLUSION: In this case the surgical approach was indicated due to the large aneurysm and the high risk of rupture.

[Relevance of an accurate microscopic examination of urinary sediment in a patient after mitral valve surgery].

Hemoglobinuria, clinically revealing as gross hematuria associated with anemia, increased hemolysis indices, acute kidney injury (AKI), can all be caused by mechanical intravascular hemolysis following mitral valve surgery. It can result from factors related to the surgical procedure or acquired later, such as paravalvular leak (PL), whose definite diagnosis is based on transesophageal echocardiography. We report the case of a patient who experienced macrohematuria and AKI, initially attributed to acute glomerulonephritis, two months after mitral valve surgery. Careful microscopic examination of the urinary sediment was a diriment diagnostic tool to differentiate acute renal failure caused by hemoglobinuria from hematuria in the course of acute glomerulonephritis, directing clinicians to investigate post-operative valvular dysfunction. From the literature review we can deduce that, notwithstanding new technologies in cardiac surgery, this rare form of AKI from intravascular hemolysis requires immediate nephrological attention and that the use of microscopic urinary sediment is decisive.

Pericardiectomy for constrictive pericarditis.

Chronic constrictive pericarditis results from inflammation and fibrosis of the pericardium. This situation eventually leads to impairment of diastolic filling and right heart failure. Once the diagnosis is made, because the disease is basically irreversible, a pericardiectomy is the mandatory treatment. The standard surgical treatment has been extensively described. The goal of this video tutorial is to render a visual explanation of the described techniques and to provide tips to help make the procedure easier to perform. The standard technique is performed through a median sternotomy, preferably without cardiopulmonary bypass if feasible. The procedure includes the complete removal of the anterior pericardium from phrenic nerve to phrenic nerve and the removal of the diaphragmatic pericardium and of part of the pericardium posterior to both phrenic nerves. Before starting the actual pericardiectomy procedure, it is useful to separate the pericardial rigid shell from the pleurae and from the diaphragm; this step allows the operator to see both phrenic nerves clearly and to give clear boundaries between the pericardium and the diaphragm, which are not often as clear as desirable due to fat, edema, inflammation, and scarring. Once a portion of the pericardium has been detached from the myocardium, it can be excised, making the portion yet to be removed more visible.

Surgical management of a free-floating thrombus in the ascending aorta.

The ascending aorta is an uncommon site of noninfective thrombus. We describe the case of a 63-year-old woman who was admitted to our department with acute myocardial infarction. Coronary angiography showed occlusion of a small diagonal vessel, likely related to a distal embolization event. A transthoracic echocardiogram revealed a free-floating mass in the proximal ascending aorta. Two-and 3-dimensional transesophageal echocardiography studies were performed, and after a multidisciplinary heart team discussion, surgical removal of the mass was planned and successfully performed through a median sternotomy on cardiopulmonary bypass.

Platypnea-orthodeoxia induced by fenestrated atrial septal aneurysm.

Platypnea-orthodeoxia is a peculiar syndrome characterized by a right-to-left shunt, which occurs in the upright position. The diagnosis is made by contrast transesophageal echocardiography, paying attention to include contrast visualization in the orthostatic decubitus. The association of this syndrome with a fenestrated atrial septal aneurysm is rare and probably underlies a peculiar and also rare mechanism of shunting in presence of normal pulmonary pressure. We report of a case of a 58-year-old man with a fenestrated atrial septal aneurysm and platypnea-orthodeoxia syndrome treated by surgical closure of the atrial defect.

[Risk evaluation in coronary surgery: a single center experience using the EuroSCORE]. / Valutazione del rischio in chirurgia coronarica: esperienza di un centro con il sistema EuroSCORE.

BACKGROUND: One of the most utilized systems for risk stratification in cardiac surgery is the EuroSCORE. It considers some risk factors that should influence the surgical risk. The aim of this study was to evaluate if our results, related to isolated coronary artery bypass surgery, are well predictable by this system and which are the parameters statistically significant for hospital mortality. METHODS: From January 1, 2002 to April 30, 2004, 724 patients underwent isolated myocardial revascularization. All risk factors considered for the EuroSCORE system evaluation and the EuroSCORE value itself were analyzed to assess their significance to predict surgical risk. Univariate statistical analysis was performed with the Student's t-test for quantitative variables and the chi2 in contingency tables for categorical variables. Logistic regression was used for multivariate analysis. RESULTS: Cumulative operative mortality was 3.7% (27 patients). The EuroSCORE value, age, critical preoperative state, emergency and low ejection fraction were all statistically significant risk factors for hospital mortality. Multivariate analysis excluded only the critical preoperative state. The analysis of contingency tables showed that the surgical risk was statistically significant above the age of 75 years. The same analysis revealed that the mortality rate was statistically different in the three groups and it showed that the system could over-estimate mortality at lower EuroSCOREs and under-estimate mortality at higher EuroSCOREs. CONCLUSIONS: This study confirms the value of the EuroSCORE for risk stratification in this group of patients. The most important parameters considered for its calculation confirmed their predictive value. This model allows a reliable quality control of our surgical practice.

Metachronous cardiac and cerebral sarcomas: case report with focus on molecular findings and review of the literature.

Although multiple primary malignancies are relatively rare, they have increased in frequency over the last decades, partly because of advances in diagnosis and therapy. This report describes for the first time the case of a patient with past occupational exposure to asbestos and no family history of cancer who developed 2 rare primary malignancies: a cardiac sarcoma and a gliosarcoma 11 months later. Molecular-cytogenetic studies did not identify common lesions to these 2 rare metachronous sarcomas. The gliosarcoma was associated with monosomy 10 and underlying PTEN monoallelic loss, which has been recurrently observed. In the cardiac sarcoma, MDM2 amplification and CDKN2AB/9p21 biallelic deletion suggested intimal sarcoma. No causal relationship was found between cardiac sarcoma and asbestos exposure, although MDM2 abnormalities were linked to malignant mesothelioma.

Nonpenetrating right atrial and pericardial trauma.

Nonpenetrating chest trauma can cause cardiac rupture. Ventricles are affected more frequently than atria. Survival is rare and depends upon prompt diagnosis and immediate surgical intervention. We report the case of a 42-year-old man involved in a car accident with consequent right atrial rupture and pericardial tearing.

Port Access Cardiac Surgery.

The port-access technique for cardiac surgery was recently developed at Stanford University in California as a less invasive method to perform some cardiac operations. The port-access system has been described in detail elsewhere. It is based on femoral arterial and venous access for cardiopulmonary bypass (CPB) and on the adoption of a specially designed triple-lumen catheter described originally by Peters, and subsequently modified and developed in the definitive configuration called the endoaortic clamp.

Heart transplantation in X-linked dilated cardiomyopathy.

BACKGROUND: X-linked dilated cardiomyopathy (DCM) is a clinical phenotype of dystrophinopathy characterized by preferential myocardial involvement without overt signs of skeletal muscle disease. X-linked DCM is a familiar myocardial disease characterized by ventricular dilation resulting in progressive heart failure and/or sudden death, and it may be differentiated from other DCMs. The aim of this retrospective study was to assess that patients with end-stage X-linked DCM can safely undergo heart transplantation. METHODS: Between August 1989 and January 2000, 7 patients presenting with X-linked DCM underwent heart transplantation for end-stage disease at our Institution. The patients' age ranged from 16 to 31 years (mean 24.4 years) and all were in NYHA functional class IV. RESULTS: The mean follow-up was 44 months (range 22-66 months). Only one sudden death occurred at 66 months of follow-up; all the other patients are doing well and are in NYHA functional class I. CONCLUSIONS: Our data suggest that heart transplantation can be considered as the treatment of choice for refractory cardiac failure in X-linked DCM.

[Surgical myocardial revascularization in patients over and under 70 years of age: results and prognostic factors]. / Rivascolarizzazione miocardica chirurgica nei pazienti di età superiore ed inferiore a 70 anni: risultati e fattori prognostici.

BACKGROUND: The increase in mean age has made older patients candidates to myocardial revascularization. This study is focused to evaluate hospital mortality and major postoperative complications in two groups of patients < or = 70 or > 70 years. The possible confounder effect of other important risk factors has been studied in multivariate models. METHODS: From January 1 to December 31, 2002, 228 patients < or = 70 years (group A) and 116 patients > 70 years (group B) underwent isolated myocardial revascularization. We analyzed the incidence of hospital mortality, cardiac failure, postoperative bleeding, major arrhythmias, atrial fibrillation, respiratory failure, renal failure, sternal infection, stroke, transient ischemic attack, total neurological complications, and number of patients with at least one of these complications. Univariate statistical analysis was used to compare this two groups and multivariate analysis to adjust for four known important risk factors, i.e. sex, diabetes, ejection fraction < 0.40, and off-pump surgical technique. RESULTS: Hospital mortality was statistically higher in group B than in group A (7.8 vs 1.7%, p < 0.05). The incidence of cardiac failure, although higher in group B, was not statistically significant. Multivariate analysis confirmed low ejection fraction as the only statistical risk factor for low cardiac output (p < 0.05). Atrial fibrillation was statistically higher in group B (p < 0.05). No difference was found for all other complications considered. Age, low ejection fraction and the use of cardiocirculatory bypass at multivariate analysis were statistically significant risk factors for the incidence of at least one postoperative event. CONCLUSIONS: Myocardial revascularization in patients > 70 years has a higher mortality and morbidity. At multivariate analysis, low ejection fraction is also confirmed as a significant risk factor for low cardiac output and total morbidity. At the same time, the technical option of "beating heart" myocardial revascularization seems to achieve better results and probably it should be used more extensively in this group of patients.

Off-pump technique: a systematic alternative for myocardial revascularization?

OBJECTIVE: Many studies failed to show that off-pump myocardial revascularization achieved better results than on-pump revascularization, and also invited a lot of criticism for the criteria used for selection and inclusion of patients. To avoid these limitations, we systematically treated all candidates for coronary surgery with this technique evaluating early and follow-up results. METHODS: In 257 prospective consecutive patients, off-pump myocardial revascularization was performed by the same surgeon without any exclusion criteria. Hospital mortality and main postoperative complications were analysed. After a mean follow-up of 27.50 months, 245 patients (98.4%) were contacted to evaluate late mortality, recurrence of angina, myocardial infarction and need for new revascularization. RESULTS: Conversion to extracorporeal circulation was necessary in 10 cases. Hospital mortality was eight patients (3.11%). Postoperative complications were reexploration for bleeding (2.72%), myocardial infarction (1.17%), atrial fibrillation (21.01%), stroke (0.39%) and renal failure (3.5%). Follow-up overall mortality was 16 patients (6.53%) with two cardiac-related deaths (0.82%). Total cardiac events at follow-up occurred in 20 patients (8.16%). There were two cardiac deaths, angina in 15 cases, silent myocardial ischaemia in two and myocardial infarction in one. New revascularization procedures were necessary in seven cases (2.86%). Statistical results showed that the European System for Cardiac Operative Risk Evaluation rate was predictor of 30-day and overall mortality. Multivariate analysis showed that age was a predictor of overall mortality whereas female sex was a predictor of cardiac events. CONCLUSION: In conclusion, systematic off-pump surgery was not associated with a higher rate of mortality, morbidity and cardiac events compared to on-pump technique.

Cyanosis in atrial septal defect without pulmonary hypertension: a case of platypnea-orthodeoxya syndrome.

Cyanosis in atrial septal defect typically occurs when pulmonary hypertension develops. Platypnea-orthodeoxya is an uncommon syndrome, still under debate, characterized by breathlessness and arterial oxygen desaturation exacerbated in the upright position. An interatrial communication is a common finding in this syndrome, but the absence of a right to left pressure gradient complicates the physiopathological picture. To explain the right to left shunt, it is generally advocated a concomitant condition that alternates the sterical relationship between inferior vena cava orifice and the atrial septal defect. A case of a 58-year-old male with platypnea-orthodeoxya syndrome related to a fenestrated redundant interatrial septum without any additional pathologic condition is reported. Possibly, this isolated anatomical abnormality could lead to a right to left shunt in the absence of other coexisting predisposing factors. It is reasonable to hypothesize the septum secundum bulging like a 'spinnaker' into the right atrium, so that it deviates the inferior vena cava venous blood towards the left atrium. Echocardiographic evaluation is mandatory to achieve a correct diagnosis and to decide the therapeutic strategy.