Mansour T. A. Sharabiani

Immunologic profile of excessive body weight

The purpose of this paper is to identify immunologic hallmarks of excessive bodyweight. The analysis is based on 176 adults (106 women, 70 men) who participated in a nested case-control study in Italy. All participants were healthy at the time of blood collection and aged between 36 and 75 years. We employed multivariate analysis of variance and a nonparametric Bayesian additive regression tree approach along with a receiver operating characteristic (ROC) curve analysis to determine the immunologic signature of excessive body weight (i.e., obesity and overweight). Interleukin 8 (IL-8), IL-10, interferon γ, and inducible protein 10 were shown to be predictive of excessive body weight with an area under the ROC curve of 71% (p < 0.0002). We propose that by using this profile-based approach to define immunologic signatures, it might be possible to identify unique immunologic hallmarks of specific types of obesity.

The intake of grain fibers modulates cytokine levels in blood

Dietary fiber may modulate the environment of the intestinal lumen, alter the intestinal microflora populations, and influence the immune response and disease risk. Epidemiological investigations have suggested that higher fiber intake is associated with lower overall mortality, in particular from cardiovascular and digestive tract diseases. Here a panel of 17 cytokines and chemokines were measured in plasma of 88 cancer-free subjects sampled within the Italian EPIC-Italy cohort. A statistically significant inverse association (p-trend = 0.01) was observed for cereal fiber and cytokines included in the main factor in factor analysis (IL-1β, IL-4, IL-5, IL-6, IL-13, and TNF-α), which alone explained 35.5% of variance. Our study suggests that fiber intake, especially cereal fiber, may be associated with a decreased level of pro-inflammatory cytokines.

Systems parasitology: effects of Fasciola hepatica on the neurochemical profile in the rat brain.

We characterize the integrated response of a rat host to the liver fluke Fasciola hepatica using a combination of 1H nuclear magnetic resonance spectroscopic profiles (liver, kidney, intestine, brain, spleen, plasma, urine, feces) and multiplex cytokine markers of systemic inflammation. Multivariate mathematical models were built to describe the main features of the infection at the systems level. In addition to the expected modulation of hepatic choline and energy metabolism, we found significant perturbations of the nucleotide balance in the brain, together with increased plasma IL‐13, suggesting a shift toward modulation of immune reactions to minimize inflammatory damage, which may favor the co‐existence of the parasite in the host. Subsequent analysis of brain extracts from other trematode infection models (i.e. Schistosoma mansoni, and Echinostoma caproni) did not elicit a change in neural nucleotide levels, indicating that the neural effects of F. hepatica infection are specific. We propose that the topographically extended response to invasion of the host as characterized by the modulated global metabolic phenotype is stratified across several bio‐organizational levels and reflects the direct manipulation of host–nucleotide balance.

Indications and results of systemic to pulmonary shunts: results from a national database

OBJECTIVES The systemic-to-pulmonary shunt (SPS) remains an important palliative therapy in many congenital heart defects. Unlike other surgical treatments, the mortality after shunt operations has risen. We used an audit dataset to investigate potential reasons for this change and to report national results. METHODS A total of 1993 patients classified in 13 diagnoses underwent an SPS procedure between 2000 and 2013. Indication trends by era and also results before repair or next stage are reported. A dynamic hazard model with competing risks and modulated renewal was used to determine predictors of outcomes. RESULTS The usage of SPS in Tetralogy of Fallot (ToF) has significantly decreased in the last decade, with cases of single ventricle (SV) and pulmonary atresia (PA) with septal communication increasing (P < 0.001 for trends). This is correlated with an increase of early mortality from 5.1% in the first half of the decade to 9.8% in the latter (P = 0.007 for trend). At 1.5 years, 13.9% of patients have died, 17.8% had a shunt reintervention and 68.3% of patients are alive and reintervention-free. Low weight, PA-intact septum, SV and central shunt type are among the factors associated with increased mortality, whereas PA-ventricular septal defect, corrected transposition, isomerism, central shunt and low weight are among those associated with increased reintervention, also having a dynamic effect on the relative risk when compared with ToF patients. Shunt reinterventions are not associated with worse outcomes when adjusted by other covariates, but they do have higher 30-day mortality if occurring earlier than 30 days from the index (P < 0.001). Patients operated in later years were found to have significantly lower survival at a distance from index. CONCLUSIONS The observed historical rise in mortality for shunt operations relates to complex factors including changing practice for repair of ToF and for univentricular palliation. PA and SV patients are the groups of patients at the highest risk of death. Small size, shunt type and underlying anatomical defect are the main determinants of outcomes. Trends in indication and mortality seem to indicate that more severely ill patients benefit from shunting, but with an increase in mortality.

Feasibility and safety of minimized cardiopulmonary bypass in major aortic surgery

OBJECTIVES Conventional cardiopulmonary bypass causes haemodilution and is a trigger of systemic inflammatory reactions, coagulopathy and organ failure. Miniaturized cardiopulmonary bypass has been proposed as a way to reduce these deleterious effects of conventional cardiopulmonary bypass and to promote a more physiological state. The use of miniaturized cardiopulmonary bypass has been reported in low-risk patients undergoing valve and coronary artery bypass graft (CABG) surgery. However, little is known about its application in major aortic surgery. METHODS From February 2007 to September 2010, 49 patients underwent major aortic surgery using the Hammersmith miniaturized cardiopulmonary bypass (ECCO, Sorin). Data were extracted from medical records to characterize preoperative comorbidities (EuroSCORE), perioperative complications and the use of blood products. The same data were collected and described for 328 consecutive patients having similar surgery with conventional cardiopulmonary bypass at the Bristol Heart Institute, our twinned centre, during the same period. RESULTS The miniaturized cardiopulmonary bypass group had a median EuroSCORE of 8 [inter-quartile range (IQR): 5-11], 13% had preoperative renal dysfunction and 20% of operations were classified as emergency or salvage. Thirty-day mortalities were 6.4; and 69, 67 and 74% had ≥ 1 unit of red cells, fresh frozen plasma (FFP) and platelets transfused, respectively. Eight percent of patients experienced a renal complication, and 8% a neurological complication. The conventional cardiopulmonary bypass group was similar, with a EuroSCORE of 8 (IQR: 6-10); 30-day mortalities were 9.4; and 68, 62 and 74% had ≥ 1 unit of red cells, FFP and platelets transfused, respectively. The proportions experiencing renal and neurological complications were 14 and 5%. CONCLUSIONS Our experience suggests that miniaturized cardiopulmonary bypass is safe and feasible for use in major aortic cardiac surgery. A randomized trial is needed to evaluate miniaturized cardiopulmonary bypass formally.

Surgery for simple and complex subaortic stenosis in children and young adults: Results from a prospective, procedure-based national database

OBJECTIVE To identify the outcomes of surgically treated subaortic stenosis in a national population. METHODS From 2000 to 2013, 1047 patients aged < 40 years underwent 1142 subaortic stenosis procedures. Of the 1047 patients, 484 (46.2%) were considered to have complex stenosis (CS) because at or before the first operation they had mitral valve (MV) disease, aortic valve disease, aortic coarctation or an interrupted aortic arch. RESULTS The 30-day mortality was 0.7% for simple stenosis (SS), 2.3% for CS (P = .06), and 1.6% overall. Age < 1 year (P < .01), MV procedure (P = .02) and an interrupted aortic arch at the index procedure (P < .01) were risk factors for early death. Konno-type procedure early mortality was 2.4%. The 12-year survival was 97.1%, with a significant difference between SS and CS (hazard ratio [HR], 4.53; P = .02). Having MV disease alone (HR, 4.11; P = .02), MV disease plus aortic coarctation (HR, 6.73; P = .008), and age < 1 year (HR, 6.72; P < .001) were risk factors for late mortality. Freedom from subaortic reintervention overall was 92.3% and 88.5% at 5 and 12 years, respectively, much greater with CS than with SS (HR, 4.91; P < .0001). The independent risk factors for reintervention were younger age at the index procedure (HR, 0.1/y; P = .002), concomitant MV procedure (HR, 2.68; P = .019), ventricular septal defect plus interrupted aortic arch (HR, 3.19; P = .014), and ventricular septal defect plus aortic coarctation (HR, 2.41; P = .023). Undergoing a concomitant aortic valve procedure at the index procedure was protective (HR, 0.29; P = .025). CONCLUSIONS Patients with SS had excellent outcomes. However, those with CS had worse long-term survival and freedom from reintervention, with morbidity and mortality greatest in young patients with multiple lesions. Additional evaluation in large-scale prospective studies is warranted.

Miniaturized cardiopulmonary bypass: the Hammersmith technique.

BackgroundConventional Cardiopulmonary Bypass (cCPB) is a trigger of systemic inflammatory reactions, hemodilution, coagulopathy, and organ failure. Miniaturised Cardiopulmonary Bypass (mCPB) has the potential to reduce these deleterious effects. Here, we describe our standardised ‘Hammersmith’ mCPB technique, used in all types of adult cardiac operations including major aortic surgery.MethodsThe use of mCPB remains limited by the diversity of technologies which range from extremely complex, micro systems to ones very similar to cCPB. Our approach is designed around the principle of balancing the benefits of miniaturisation; reducing foreign surface area while maintaining patient safety.ResultsFrom January 2010 to March 2011, a single surgeon performed 184 consecutive operations (Euro score Logistic 8.4+/-9.9): 61 aortic valve replacements, 78 CABGs, 25 aortic valve replacement and CABG and 17 other procedures (major aortic surgery, re-do operations or double/triple valve replacements).Our clinical experience suggests that:i.Venous drainage is optimally maintained using kinetic energy.ii.Venous collapse pressure depends on the patient’s anatomy and cannula size, but most importantly on the negative pressure generated by venous drainage.iii.The patient-prime interaction is optimised with antegrade and retrograde autologous priming, which mixes the blood and prime away from the tissues and results in a reduced oncotic destabilization.iv.mCPB is a safe and reproducible techniqueConclusionThe Hammersmith mCPB is a “next generation” system which uses standard commercially available components. It aims to maintain safety margin and the benefit of miniaturised system whilst reducing the human factor demands.

Outcomes following repair of anomalous coronary artery from the pulmonary artery in infants: results from a procedure-based national database

Background Anomalous coronary artery from the pulmonary artery (ACAPA) is a very rare congenital anomaly that often occurs during infancy. Patients can present in a critical condition. Methods We analysed procedure-related data from a national audit database for the period 2000–2013. Results A total of 120 patients <1 year had repair of isolated ACAPA using a coronary transfer or the tunnel (Takeuchi) operation. Seven patients (6.8%) required a mitral valve procedure at index and eight patients (7.8%) had a mitral valve repair/replacement during follow-up, including mitral reoperations. Follow-up data (>30 days) were available in 102 patients and the mean follow-up time was 4.7 years. The 30-day overall mortality was 1.9%, higher for neonates (16.7% vs 1%, p=0.1) and after postoperative extracorporeal membrane oxygenation (ECMO) (20% vs 1%, p=0.09). At 10 years the survival estimate is 95.1%, freedom from coronary and mitral reintervention being 95.9% and 91.2%, respectively. Use of postoperative ECMO was a risk factor for long-term mortality (p<0.001). Risk factors for coronary reintervention were age under 30 days (p=0.06) and the need for postoperative ECMO (p=0.02). Age under 30 days (p=0.002) was a risk factor for mitral reintervention. Conclusions To our knowledge this is the largest series to date. These preliminary national results show that early outcomes are good and medium-term attrition acceptable. Poor outcomes are correlated with early presentation, also with the need for postoperative circulatory support.

P9 Indications and results of systemic to pulmonary shunts – results from a national database

Objective The systemic-to-pulmonary shunt (SPS) remains an important palliative therapy in many congenital heart defects. Unlike other surgical treatments, the mortality after shunt operations has risen. We used an audit dataset to investigate potential reasons for this change and to report national results. Patients and methods A total of 1993 patients classified in 13 diagnoses underwent an SPS procedure between 2000 and 2013. Indication trends by era and also results before repair or next stage are reported. A dynamic hazards model with competing risks and modulated renewal were used to determine predictors of outcomes. Results Usage of SPS in Tetralogy of Fallot (ToF) has significantly decreased, in the last decade, with cases of single ventricle (SV) and pulmonary atresia (PA) with septal communication increasing (p < 0.001 for trends). This is correlated with an increase of early mortality from 5.1% in the first half of the decade to 9.8% in the latter (p = 0.007 for trend). At 1.5 years, 13.9% of patients have died, 17.8% had a shunt reintervention and 68.3% of patients are alive and reintervention-free. Survival and freedom from reintervention in the main diagnosis groups can be seen in Figures A and B. Low weight, PA-IVS, SV and central shunt type are among the factors associated with increased mortality, while PA-VSD, corrected transposition, isomerism, central shunt and low weight are among those associated with increased reintervention, also having a dynamic effect on the relative risk when compared to ToF patients. Shunt reinterventions are not associated with worse outcomes when adjusted by other covariates, but they do have higher 30-day mortality if occurring earlier than 30 days from the index (p < 0.001). Patients operated in later years were found to have significantly lower survival at distance from index. Abstract P9 Figure 1 Freedom from death (panel A), or reintervention (panel B) following placement of a systemic to pulmonary shunt. Conclusions The observed historical rise in mortality for shunt operations relates to complex factors including changing practice for repair of ToF and for univentricular palliation. PA and SV patients are the groups of patients at the highest risk of death. Small size, shunt type and underlying anatomical defect are the main determinants of outcomes. Trends in indication and mortality seem to point that more severely ill patients benefit from shunting, but with an increase in mortality.