ATSC transplantation contributes to liver regeneration following paracetamol-induced acute liver injury through differentiation into hepatic-like cells.

INTRODUCTION: Drug-induced liver injury (DILI) is a leading cause of acute liver injury (ALI). Acetaminophen (also termed paracetamol), can often be found in drugs that may be abused (i.e., prescription for pain relief). Animal experiments have shown that mesenchymal stem cell transplantation can ameliorate or even reverse hepatic injury. MATERIAL AND METHODS: ALI was induced in Wistar rats using paracetamol. ATSCs were transplanted via the intravenous, portal vein, or intrahepatic route directly onto the liver parenchyma. Histological evaluation was conducted to assess drug-induced injury following transplantation. Fluorescence in situ hybridization (FISH) was used to verify the location of stem cells on the liver parenchyma. The effect of those cells on liver regeneration was tested by immunohistochemistry for hepatic growth factor (HGF). In addition, reverse transcription-quantitative PCR (qRT-PCR) was used to assess hepatic growth factor (HGF), hepatic nuclear factor 4α (HNF4α), cytochrome P450 1A2 (CYP1A2) and α-fetoprotein (AFP) mRNA expression. RESULTS: Immunohistochemical staining for HGF was stronger in the transplanted groups than that in the control group (P<0.001). HNF4α and HGF mRNA levels were increased on day 7 following transplantation (P<0.001 and P=0.009, respectively). CYP1A2 mRNA levels were also increased (P=0.013) in the intravenous groups, while AFP levels were higher in the intrahepatic groups (P=0.006). ATSC transplantation attenuates ALI injury and promotes liver regeneration. Furthermore, expression of specific hepatic enzymes points to ATSC hepatic differentiation. CONCLUSION: The study showed the positive effects of transplanted adipose tissue stem cells (ATSCs) on liver regeneration (LG) through hepatotrophic factors. Furthermore, increased expression of hepatic specific proteins was recorded in ATSC transplanted groups that indicate stem cells differentiation into hepatic cells.

Predictors of Outcomes after Correction of Acute Type A Aortic Dissection under Moderate Hypothermic Circulatory Arrest and Antegrade Cerebral Perfusion.

INTRODUCTION: Hypothermic circulatory arrest is widely used for correction of acute type A aortic dissection pathology. We present our experience of 45 consecutive patients operated in our unit with bilateral antegrade cerebral perfusion and moderate hypothermic circulatory arrest. METHODS: Between January 2011 and April 2015, 45 consecutive patients were admitted for acute type A aortic dissection and operated emergently under moderate hypothermic circulatory arrest and bilateral antegrade cerebral perfusion. RESULTS: Mean age was 58±11.4 years old. Median circulatory arrest time was 41.5 (30-54) minutes while the 30-day mortality and postoperative permanent neurological deficits rates were 6.7% and 13.3%, respectively. Unadjusted analysis revealed that the factors associated with 30-day mortality were: preoperative hemodynamic instability (OR: 14.8, 95% CI: 2.41, 90.6, P=0.004); and postoperative requirement for open sternum management (OR: 5.0, 95% CI: 1.041, 24.02, P=0.044) while preoperative hemodynamic instability (OR: 8.8, 95% CI: 1.41, 54.9, P=0.02) and postoperative sepsis or multiple organ dysfunction (OR: 13.6, 95% CI: 2.1, 89.9, P=0.007) were correlated with neurological dysfunction. By multivariable logistic regression analysis, postoperative sepsis and multiple organ dysfunction independently predicted (OR: 15.9, 95% CI: 1.05, 96.4, P=0.045) the incidence of severe postoperative neurological complication. During median follow-up of 6 (2-12) months, the survival rate was 86.7%. CONCLUSION: Bilateral antegrade cerebral perfusion and direct carotid perfusion for cardiopulmonary bypass, in the surgical treatment for correction of acute aortic dissection type A, is a valuable technique with low 30-day mortality rate. However, postoperative severe neurological dysfunctions remain an issue that warrants further research.

Undifferentiated Adipose Tissue Stem Cell Transplantation Promotes Hepatic Regeneration, Ameliorates Histopathologic Damage of the Liver, and Upregulates the Expression of Liver Regeneration- and Liver-Specific Genes in a Rat Model of Partial Hepatectomy.

OBJECTIVE: Adipose tissue stem cells (ADSCs) present a promising therapeutic method to alleviate liver failure (LF). The purpose of this prospective study was to evaluate the efficacy of undifferentiated ADSC transplantation on liver regeneration and on the expression of liver regeneration- and liver-specific genes, following 60% partial hepatectomy (PHx). METHODS: Sixty female rats were subjected to PHx and were transplanted with 106 or 2 × 106 ADSCs, either into the portal vein (PV) or into the hepatic parenchyma. Animals of the control group were not transplanted and served as controls. Animals were sacrificed on the 4th, the 7th, or the 15th postoperative day (POD). RESULTS: The transplanted ADSCs were successfully engrafted into the liver parenchyma and ameliorated the histopathologic damage on the 7th and 15th POD. All transplanted animals demonstrated a significantly higher liver regeneration rate on the 4th and 7th POD, compared with the control group. The expression of hepatocyte growth factor, α-fetoprotein, tyrosine aminotransferase, hepatocyte nuclear factor 4a, and cytochrome P450 1A2 was significantly upregulated, compared with the control group. CONCLUSIONS: Although undifferentiated, ADSC transplantation significantly enhanced the liver regeneration process. These findings may be proven clinically valuable, especially in cases of acute LF.

Predictors of outcomes after correction of acute type a aortic dissection under moderate hypothermic circulatory arrest and antegrade cerebral perfusion

Abstract Introduction: Hypothermic circulatory arrest is widely used for correction of acute type A aortic dissection pathology. We present our experience of 45 consecutive patients operated in our unit with bilateral antegrade cerebral perfusion and moderate hypothermic circulatory arrest. Methods: Between January 2011 and April 2015, 45 consecutive patients were admitted for acute type A aortic dissection and operated emergently under moderate hypothermic circulatory arrest and bilateral antegrade cerebral perfusion. Results: Mean age was 58±11.4 years old. Median circulatory arrest time was 41.5 (30-54) minutes while the 30-day mortality and postoperative permanent neurological deficits rates were 6.7% and 13.3%, respectively. Unadjusted analysis revealed that the factors associated with 30-day mortality were: preoperative hemodynamic instability (OR: 14.8, 95% CI: 2.41, 90.6, P=0.004); and postoperative requirement for open sternum management (OR: 5.0, 95% CI: 1.041, 24.02, P=0.044) while preoperative hemodynamic instability (OR: 8.8, 95% CI: 1.41, 54.9, P=0.02) and postoperative sepsis or multiple organ dysfunction (OR: 13.6, 95% CI: 2.1, 89.9, P=0.007) were correlated with neurological dysfunction. By multivariable logistic regression analysis, postoperative sepsis and multiple organ dysfunction independently predicted (OR: 15.9, 95% CI: 1.05, 96.4, P=0.045) the incidence of severe postoperative neurological complication. During median follow-up of 6 (2-12) months, the survival rate was 86.7%. Conclusion: Bilateral antegrade cerebral perfusion and direct carotid perfusion for cardiopulmonary bypass, in the surgical treatment for correction of acute aortic dissection type A, is a valuable technique with low 30-day mortality rate. However, postoperative severe neurological dysfunctions remain an issue that warrants further research.

Outcomes after a left anterior descending artery endarterectomy in advanced coronary artery disease.

BACKGROUND: Coronary endarterectomy albeit infrequently utilized remains a pivotal treatment modality for advanced atherosclerotic heart disease. Benefits of coronary endarterectomy are explored in terms of better mid-term survival, freedom of major adverse cardiac and cerebrovascular events and improved left ventricular ejection fraction. METHODS: 50 patients with coronary artery disease including extensive diffuse LAD disease underwent a left anterior descending artery endarterectomy with coronary by-pass grafting and left internal mammary artery as conduit between 2006 and 2014. Prospective evaluation was performed on an outpatient basis with physical examination, echo recordings of ejection fraction and LAD flow reserve for 24 up to 60months. RESULTS: Study group was constituted by a male to female ratio 4:1 and mean age 62.4years old. Pre-operative characteristics included patients with age<60years old and gensini score>60 in 42.1% while patients with age>60years old had gensini score (21-60) in 63.4%. Furthermore, males were affected more severely by atherosclerosis than females. Postoperative anterior wall contractility of left ventricle was improved (56% pre-op vs. 66% post-op) and hypokinesis reduced (34% pre-op vs. 24% post-op). No deaths were recorded for a mean follow-up of 48months. Also, MACCE were recorded in 8% patients. Post-operative LAD flow reserve was normal in 66% and reduced in 33% of cases. Finally, gensini score preoperatively affects mid-term flow reserve postoperatively (p<0.05). CONCLUSION: Coronary endarterectomy presents a viable modality that preserves myocardial function and restores LAD flow in patients with diffuse atherosclerotic LAD. Also postoperative adverse effects were minimal while mid-term flow reserve was affected by preoperative factors.

Unusual Location of a Cardiac Papillary Fibroelastoma.

Cardiac papillary fibroelastoma is a rare benign cardiac tumor that represents less than 10% of all cardiac tumors. Most papillary fibroelastomas are relatively small. Symptoms, if present, are due to flow obstruction or peripheral embolization. The most common sites of origin are aortic and mitral valve surfaces. We present successful surgical resection of a papillary fibroelastoma through the mitral valve which originated from the posterior papillary muscle of the left ventricle.

Long-Term Results after Modified Bentall Operation in 200 Patients.

BACKGROUND: Composite graft replacement of the aortic root is the treatment of choice for an array of aortic root pathologies, such as annuloaortic ectasia, Marfan syndrome and acute or chronic aortic dissection type A. In this retrospective study of the authors' aortic surgery database, an exploration was made of factors related to early and long-term morbidity and mortality of patients who underwent this procedure. METHODS: Between 2000 and 2009, a total of 200 consecutive patients (male:female ratio 4:1; mean age 56.2 ± 11.66 years) underwent the modified Bentall operation at the authors' institution, with a composite graft (mechanical valve) being used to correct aortic root pathology. All preoperative, perioperative and postoperative data, as well as long-term follow up data, were retrieved from the authors' aortic surgery database. RESULTS: Preoperative characteristics of the patients included elective and emergency operations (83.1% and 15.9%, respectively). Intraoperative and 30-day mortalities were 2% and 3.5%, respectively, while the rate of postoperative cerebrovascular events was 1.5%. Long-term survival at a mean follow up of 110 months for the elective and emergency groups was 88.6% and 71.9%, respectively (p = 0.007). Moreover, during the same period new cerebrovascular events were observed in 5.8% of cases. Predictive factors for late survival were type of surgery (elective versus emergency; p = 0.023), conduit size (≤23 mm versus >23 mm; p = 0.053) , age >65 years (p = 0.001), intensive care unit stay (days; p <0.001) and postoperative creatinine level (p = 0.002). Survival rates at one, three, five and 10 years postoperatively were 93.5%, 92.5%, 91.5% and 85.9%, respectively. CONCLUSIONS: Patients who underwent the modified Bentall operation presented with minimal major adverse effects and demonstrated a good long-term survival.

Role of Stem Cells Transplantation in Tissue Regeneration After Acute or Chronic Acetaminophen Induced Liver Injury.

PURPOSE: Acetaminophen-induced liver injury (APAP) is recognized as a frequent etiologic factor responsible for hepatic damage in the developed world. Management remains still elusive as treatment options are limited and their results are inconclusive. Consequently new strategies are explored at the experimental level. Mesenchymal stem cells (MSCs) present a promising modality as they can promote liver regeneration (LG) and compensate acute liver injury (ALI). MATERIALS AND METHODS: Our research was focused on articles related to drug-induced liver injury, mechanisms of liver regeneration (LG) after Acute Liver Injury (ALI) and recent experimental protocols of Mesenchymal Stem Cells (MSCs) transplantation after chemical insult. All these studies are cited on Pubmed and MedLine. RESULTS: This review has three distinct sections. First recent developments in ALI pathogenesis are presented. The second section covers cellular pathways and histological findings relevant to liver regeneration. The final chapter analyzes MSCs transplantation protocols after ALI and interrelation between liver regeneration and hepatic differentiation of MSCs. CONCLUSION: Adipose tissue stem cells (ADSCs) and (MSCs) transplantation represents a promising modality in severe ALI management although many aspects remain to be clarified.