Orexigenic Hormone Ghrelin Attenuates Local and Remote Organ Injury after Intestinal Ischemia-Reperfusion

Gut ischemia/reperfusion (I/R) injury is a serious condition in intensive care patients. Activation of immune cells adjacent to the huge endothelial cell surface area of the intestinal microvasculature produces initially local and then systemic inflammatory responses. Stimulation of the vagus nerve can rapidly attenuate systemic inflammatory responses through inhibiting the activation of macrophages and endothelial cells. Ghrelin, a novel orexigenic hormone, is produced predominately in the gastrointestinal system. Ghrelin receptors are expressed at a high density in the dorsal vagal complex of the brain stem. In this study, we investigated the regulation of the cholinergic anti-inflammatory pathway by the novel gastrointestinal hormone, ghrelin, after gut I/R.Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 90 min in male adult rats. Our results showed that ghrelin levels were significantly reduced after gut I/R and that ghrelin administration inhibited pro-inflammatory cytokine release, reduced neutrophil infiltration, ameliorated intestinal barrier dysfunction, attenuated organ injury, and improved survival after gut I/R. Administration of a specific ghrelin receptor antagonist worsened gut I/R-induced organ injury and mortality. To determine whether ghrelin's beneficial effects after gut I/R require the intact vagus nerve, vagotomy was performed in sham and gut I/R animals immediately prior to the induction of gut ischemia. Our result showed that vagotomy completely eliminated ghrelin's beneficial effect after gut I/R. To further confirm that ghrelin's beneficial effects after gut I/R are mediated through the central nervous system, intracerebroventricular administration of ghrelin was performed at the beginning of reperfusion after 90-min gut ischemia. Our result showed that intracerebroventricular injection of ghrelin also protected the rats from gut I/R injury.These findings suggest that ghrelin attenuates excessive inflammation and reduces organ injury after gut I/R through activation of the cholinergic anti-inflammatory pathway

How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

Traumatic Injuries to the Pregnant Patient: A Critical Literature Review

INTRODUCTION: Trauma during pregnancy is the leading non-obstetrical cause of maternal death and a significant public health burden. This study reviews the most common causes of trauma during pregnancy, morbidity, and mortality, and the impact upon perinatal outcomes associated with trauma, providing a management approach to pregnant trauma patients. MATERIALS AND METHODS: A systematic review of the current literature from January 2006 to July 2016 was performed. RESULTS: Fifty-one articles were identified, including a total of 95,949 patients. Motor vehicle crash was the most frequent cause of blunt trauma, followed by falls, assault both domestic and interpersonal violence, and penetrating injuries (gunshot and stab wounds). CONCLUSIONS: Trauma in pregnant women is associated with high rates of adverse maternal and neonatal outcomes. Knowledge of the mechanism of injury is important to identify the potential injuries and the complexity of the management of these patients. As in all traumatic events, prevention is of paramount importance

Comparison Between Thromboelastography and Conventional Coagulation Test: Should We Abandon Conventional Coagulation Tests in Polytrauma Patients?

INTRODUCTION: TEG provides an in-vivo assessment of viscoelastic clot strength in whole blood compared with CCT, which may not reflect the influence of platelets. The aim of this study was to compare TEG vs. CCT in trauma patients stratified by mechanism of injury (MOI) and pre-existing coagulation status. METHODS: A retrospective, observational study of 230 polytrauma patients admitted to a University Hospital Level 1 Trauma Center, with TEG and CCT on admission stratified by MOI: multiple trauma (MT), isolated traumatic brain injury (TBI) or MT+TBI. Statistical analysis included correlation between TEG and CCT in all groups and a subgroup analysis of anticoagulated patients. Data were analyzed with ANOVA, Spearman and lineal regression when appropriate. Statistical significance was accepted at P\u3c0.05. RESULTS: TEG was normal in 28.7%, hypercoagulable in 68.3%, hypocoagulable in 7%. There was no difference in TEG status among the groups. The coagulation status was not affected by age, ISS or shock. The CCT were abnormal in 63.6% of patients with normal TEG. Normal or hypercoagulable-TEG was found in 21/23 patients on Coumadin who had elevated INR and in 10/11 patients on NOAC. An analysis of the 23 patients on Coumadin stratified by INR showed a normal or hypercoagulable-TEG in 21/23 patients. Only 2 patients had a hypocoagulable-TEG. Mortality was 5.2% (58.3% severe TBI). CONCLUSIONS: TEG is more useful than CCT in polytrauma patients, including patients on anticoagulants. TBI could increase the incidence of hypercoagulability in trauma. CCT are not useful from the standpoint of treatment

Systemic Lupus Erythematosus-associated Thrombocytopenia in Pregnancy: Is Splenectomy Necessary at the Time of Delivery?

Systemic lupus erythematosus (SLE)-associated thrombocytopenia in pregnancy is a rare condition associated with potential harm to the mother, the fetus, and/or newborn, if the thrombocytopenia is severe (\u3c50,000/mm3). Controversy persists regarding the role and the timing of splenectomy in patients with SLE-associated refractory immune thrombocytopenia in pregnancy. This report describes the use of splenectomy at the time of the cesarean section (CS) in a patient with refractory SLE-associated thrombocytopenia

In-Site Monocyte Implantation in Bone Grafting for Maxillary Atrophy Reconstruction: A Preliminary Observational Proof of Concept Study

PURPOSE: The main objective of this study, involving 11 patients, is to share our experience on an integrated treatment modality, namely, the use of cellular therapy simultaneously with surgical reconstruction. Published works show that the implantation of monocytes in ischemic tissue enhances healing by providing neo-angiogenesis, a key mechanism in tissue regenerative processes. MATERIALS AND METHODS: Our approach included the utilization of autologous monocytes and endothelial precursor cells in the bone graft itself to improve the success rate of the integration of the bone graft and its long-term viability/survival by promoting angiogenesis. We compared the standard regenerative procedures, namely sinus lift grafting performed with xenogeneic particle bone graft and posterior mandible grafting performed with on-lay or in-lay autologous cortical/medullary bone-block graft harvested from the iliac crest, with and without the use of cellular implementation. We evaluated results by both radiological and histological assessment. RESULTS: Autologous cortical/medullary bone-block graft had a different response to implementation with monocytes, showing a better osteointegration than expected conversely to the xenogeneic particle bone graft. CONCLUSIONS: Monocytes seem to improve autologous bone-block graft according to the Therapeutic Angiogenesis concept. Implementation with monocytes does not always improve xenogeneic particle bone graft

Correlation of Brain Flow Variables and Metabolic Crisis: A Prospective Study in Patients With Severe Traumatic Brain Injury

INTRODUCTION: Current treatment guidelines for patients with severe TBI (sTBI) are aimed at preventing secondary brain injury targeting specific endpoints of intracranial physiology to avoid the development of metabolic crisis. We sought to identify factors contributing to development of metabolic crisis in the setting of a Multi-modality Monitoring and Goal-Directed Therapy (MM&GDTP) approach to patients with severe TBI. METHODS: Prospective monitoring of sTBI patients was performed, with retrospective data analysis. MM&GDTP was targeted to intracranial pressure (ICP) ≤ 20 mmHg, cerebral perfusion pressure (CPP) ≥ 60 mmHg, brain tissue oxygen pressure (PbtO) ≥ 20 mmHg, and cerebral oxygen extraction measured by bi-frontal Near infrared Spectroscopy (NIRS) \u3e 55%. Brain flow abnormality was defined by one of the following combinations: CPP \u3c 60 mmHg with NIRS \u3c 55% (Type 1), CPP \u3c 60 mmHg with PbtO \u3c 20 mmHg (Type 2), or PbtO \u3c 20 mmHg with NIRS \u3c 55% (Type 3). Cerebral micro-dialysate was analyzed hourly for glucose, lactate, pyruvate, glutamate, glycerol, and lactate/pyruvate ratio (LPR). Statistical analysis was performed with student t-test, chi-square and Pearson\u27s tests as applicable. RESULTS: A total of 109,474 consecutive minutes of recorded multimodality monitoring was available for analysis. There was a significant difference in the number of minutes of brain flow abnormalities between survivors and non-survivors: 0.8% (875) versus 7.49% (8,199), respectively (p \u3c 0.05). The duration of Type 1-3 flow abnormality per patient was higher in non-survivors (5.7 ± 2.5 h) compared to survivors (0.7 ± 0.6 h) as well as the duration of metabolic crisis, namely, 5.2 ± 2.2 versus 0.6 ± 1.0 h per patient. The occurrence of severe metabolic crisis was associated with a Type 2 flow abnormality (CPP \u3c 60 mmHg and PbtO \u3c 20 mmHg), r = 0.97, p \u3c 0.001, but not with Type 1 and 3. CONCLUSIONS: Metabolic crisis can occur despite a MM&GDTP approach aimed at optimizing cerebral blood flow. Severe metabolic crisis is associated to failure to maintain CPP and PbtO above 60 and 20 mmHg, respectively The occurrence of severe metabolic crisis portends a poor prognosis in patients with sTBI