Intestinal Fatty Acid-Binding Protein as a Potential Biomarker for Gastrointestinal Complications after Complex Endovascular Aortic Surgery.

BACKGROUND: This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair. METHODS: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care. RESULTS: Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008). CONCLUSIONS: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients.

Intra-aortic and Intra-caval Balloon Pump Devices in Experimental Non-traumatic Cardiac Arrest and Cardiopulmonary Resuscitation.

Intra-aortic balloon pump (IABP) use during CPR has been scarcely studied. Intra-caval balloon pump (ICBP) may decrease backward venous flow during CPR. Mechanical chest compressions (MCC) were initiated after 10 min of cardiac arrest in anesthetized pigs. After 5 min of MCC, IABP (n = 6) or ICBP (n = 6) was initiated. The MCC device and the IABP/ICBP had slightly different frequencies, inducing a progressive peak pressure phase shift. IABP inflation 0.15 s before MCC significantly increased mean arterial pressure (MAP) and carotid blood flow (CBF) compared to inflation 0.10 s after MCC and to MCC only. Coronary perfusion pressure significantly increased with IABP inflation 0.25 s before MCC compared to inflation at MCC. ICBP inflation before MCC significantly increased MAP and CBF compared to inflation after MCC but not compared to MCC only. This shows the potential of IABP in CPR when optimally synchronized with MCC. The effect of timing of intra-aortic balloon pump (IABP) inflation during mechanical chest compressions (MCC) on hemodynamics. Data from12 anesthetized pigs.

Intestinal fatty acid-binding protein and acute gastrointestinal injury grade in postoperative cardiac surgery patients.

BACKGROUND AND AIM: Gastrointestinal complications post cardiac surgery are infrequent but difficult to diagnose and carry a high mortality. Plasma intestinal fatty acid-binding protein (I-FABP) concentrations and the relationship between I-FABP, gastrointestinal dysfunction, and postoperative outcomes were investigated in patients who developed gastrointestinal dysfunction (acute gastrointestinal injury [AGI] grade ≥2) and those with normal gastrointestinal function. METHODS: Patients with (AGI 2 group, n = 11) and without (matched controls, AGI 0 group, n = 22) early postoperative gastrointestinal dysfunction were extracted from a larger single-center prospective observational study, including adults undergoing elective cardiac surgery with extracorporeal circulation, and investigated in this nested case-control analysis. RESULTS: Both groups displayed variations in I-FABP concentrations with higher I-FABP on postoperative Day 1 compared to baseline and postoperative Days 2 and 3 (p < .001 and p = .005, respectively). The AGI 2 group had higher I-FABP concentrations on Day 2 compared to the AGI 0 group (p = .024). I-FABP on Day 2 correlated positively with AGI grade over the first 3 days (p = .036, p = .021 and p = .018, respectively). High I-FABP (defined as fourth quartile concentrations) on Day 1 was associated with more prolonged surgical procedures (p < .05). Furthermore, fourth quartile I-FABP on Day 1 and early gastrointestinal dysfunction were associated with higher frequencies of postoperative organ dysfunction (p < .05) and gastrointestinal complications (p < .05), and higher 365-day mortality. CONCLUSION: The present study indicates an association between intraoperative gastrointestinal injury, postoperative gastrointestinal dysfunction and gastrointestinal complications. A high-powered study is needed to further explore this relationship and the interpretation of I-FABP concentrations in individual cardiac surgery patients.

Early Onset of Postoperative Gastrointestinal Dysfunction Is Associated With Unfavorable Outcome in Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: The distribution of postoperative gastrointestinal (GI) dysfunction and its association with outcome were investigated in cardiac surgery patients. Gastrointestinal function was evaluated using the Acute Gastrointestinal Injury (AGI) grade proposed by the European Society of Intensive Care Medicine. DESIGN: Prospective observational study at a single center. SETTING: University hospital. PATIENTS: Consecutive patients presenting for elective cardiac surgery with extracorporeal circulation (ECC). INTERVENTIONS: None. RESULTS: Daily assessment using the AGI grade was performed on the first 3 postoperative days in addition to standard care. For analysis, 3 groups were formed based on the maximum AGI grade: AGI 0, AGI 1, and AGI ≥2. Five hundred and one patients completed the study; 32.7%, 65.1%, and 2.2% of the patients scored a maximum AGI 0, AGI 1, and AGI ≥2, respectively. Patients with AGI grade ≥2 had more frequently undergone thoracic aortic surgery and had longer surgery duration and time on ECC. Patients with AGI grade ≥2 had statistically significant higher frequency of GI complications within 30 days (63.6% vs 1.2% and 5.5% in patients with AGI 0 and AGI 1) and higher 30-day mortality (9.1% vs 0.0% and 1.8% in patients with AGI 0 and AGI 1). CONCLUSIONS: Early GI dysfunction following cardiac surgery was associated with an unfavorable outcome. Increased attention to GI dysfunction in cardiac surgery patients is warranted and the AGI grade could be a helpful adjunct to a structured approach.

Resuscitative endovascular balloon occlusion of the aorta in zone I versus zone III in a porcine model of non-traumatic cardiac arrest and cardiopulmonary resuscitation: A randomized study.

INTRODUCTION: Resuscitative endovascular balloon occlusion of the aorta (REBOA) in zone I increases systemic blood pressure during cardiopulmonary resuscitation (CPR), while also obstructing the blood flow to distal organs. The aim of the study was to compare the effects on systemic blood pressure and visceral blood flow of REBOA-III (zone III, infrarenal) and REBOA-I (zone I, supraceliac) during non-traumatic cardiac arrest and CPR. METHODS: Cardiac arrest was induced in 61 anesthetized pigs. Thirty-two pigs were allocated to a hemodynamic study group where the primary outcomes were systemic arterial pressures and 29 pigs were allocated to a blood flow study group where the primary outcomes were superior mesenteric arterial (SMA) and internal carotid arterial (ICA) blood flow. After 7-8 min of CPR with a mechanical compression device, REBOA-I, REBOA-III or no aortic occlusion (control group) were initiated after randomization. RESULTS: Systemic mean and diastolic arterial pressures were statistically higher during CPR with REBOA-I compared to REBOA-III (50 mmHg and 16 mmHg in REBOA-I vs 38 mmHg and 1 mmHg in REBOA-III). Systemic systolic, mean and diastolic arterial pressures were statistically elevated during CPR in the REBOA-I group compared to the controls. The SMA blood flow increased by 49% in REBOA-III but dropped to the levels of the controls within minutes. The ICA blood flow increased the most in REBOA-I compared to REBOA-III and the control group (54%, 19% and 0%, respectively). CONCLUSION: In experimental non-traumatic cardiac arrest and CPR, REBOA-I increased systemic blood pressures more than REBOA-III, and the potential enhancement of visceral organ blood flow by REBOA-III was short-lived.

Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment.

BACKGROUND: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. METHODS: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. RESULTS: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. CONCLUSIONS: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.

BACKGROUND: Changes in the blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks. METHODS: A broad panel of markers for lymphocyte populations, including states of activation and co-stimulation, as well as functional T cell responses to recall antigens and mitogens, were assessed by flow cytometry in 40 patients with relapsing multiple sclerosis before and after one-year natalizumab treatment. RESULTS: Absolute numbers of all major lymphocyte populations increased after treatment, most markedly for NK and B cells. The fraction of both memory and presumed regulatory B cell subsets increased, as did CD3(-)CD56(dim) cytotoxic NK cells, whereas CD3(-)CD56(bright) regulatory NK cells decreased. The increase in cell numbers was further associated with a restored T cell responsiveness to recall antigens and mitogens in functional assays. CONCLUSIONS: Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK and B cells. This finding supports reduction of lymphocyte extravasation as a main mode of action, although the differential effects on subpopulation composition suggests that cell-signalling may also be affected. The systemic increase in T cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses may become correspondingly decreased.