MicroRNA Let-7a association with glycolysis-induced autophagy in locally advanced gastric cancer: Their role in prognosis and FLOT chemotherapy resistance.

Locally advanced gastric cancer (LAGC) still poses a clinical challenge despite multimodality treatment due to multidrug resistance (MDR). Recently, research suggested that autophagy and metabolic regulation may be potential anticancer targets due to their crucial roles in MDR. Let-7a participates in glycolytic and autophagic regulations which are both essential for tumor progression and resistance to therapy. This study used IHC stains; GLUT4 and LC3B to evaluate glycolysis and autophagy respectively. Moreover, mRNA Let-7a was detected by quantitative reverse transcription PCR (q-PCR) in 53 cases of LAGC. Elevated glycolysis and autophagy in LAGC tissue specimens as indicated by high GLUT4 and LC3B expression were significantly associated with adverse prognostic factors such as high pathological grade, positive nodal metastasis, and advanced T stage. Lower Let-7a levels were significantly associated with high tumor grade and advanced T stage. A significant positive correlation between GLUT4 and LC3B expression was detected. Significant inverse correlations between let7a level and IHC expression of both GLUT4 and LC3B were found. Elevated glycolysis and autophagy were significantly associated with poor overall survival (OS). Furthermore, low levels of let-7a were significantly associated with poor OS compared to high levels. Glycolysis and autophagy in LAGC were significantly associated with poor FLOT chemotherapy response. Let7a mRNA relative expression was significantly decreased in cases showing post therapy partial response and sustained disease. Multivariate analysis showed that histologic tumor type, high GLUT4 and high LC3B expression were independent factors associated with poor OS. Poor survival and post FLOT chemotherapy resistance in LAGC cases were significantly related to elevated glycolysis, elevated autophagy, and reduced Let-7a expression. Accordingly, combined therapeutic targeting of these pathways could enhance chemosensitivity in LAGC.

Effect of Fast Cardioplegic Arrest Induced by Adenosine on Cardiac Troponin Levels After Heart Valve Surgery.

BACKGROUND: Cellular injury is not avoidable with current cardioplegic solutions. The effect of adenosine on reducing cardiac injury post-surgery is controversial. The objective of the current study is to evaluate the effect of fast cardioplegic arrest induced by adenosine on high sensitive cardiac troponin I after heart valve surgery. METHODS: Forty-five (45) patients with rheumatic heart diseases underwent heart valve surgery using conventional approach through median sternotomy. They were classified into two groups, group I (n=21) patients received 0.25mg/kg adenosine into the aortic root just after aortic cross-clamping and before infusion of the cold hyperkalaemic crystalloid cardioplegia via antegrade route and group II (n=24) who received cold crystalloid hyperkalaemic cardioplegia without adenosine. Cardiac troponin I was measured preoperatively and on postoperative days 0, 3 and 7. RESULTS: There was no significant difference between both groups in the demographic, preoperative and operative data. Adenosine significantly reduced arrest time. Postoperative high sensitive cardiac troponin I increased significantly in both groups compared to the preoperative levels and the rise continued till postoperative day 3. Troponin levels were significantly lower in the adenosine group compared to the control at all measurements. The clinical outcomes were non-significant different between groups. CONCLUSIONS: Using adenosine in inducing fast cardioplegic arrest in heart valve surgery after aortic cross clamp and prior to infusion of the cold cardioplegia had significantly decreased postoperative cardiac troponin levels which was used as a proxy for cellular injury compared to the control group.

Evaluation of local intra-pleural application of tranexamic acid on postoperative blood loss in lung decortication surgery, a prospective, randomized, double-blind, placebo-controlled study.

Background: During decortication surgery, fibrous peel over the lung was removed to allow expansion of the lung and therefore, wide raw area was created with surface oozing. The phenomenon of fibrinolysis usually activated after such procedure, resulting in increasing the postoperative bleeding. Tranexamic acid is one of antifibrinolytic therapies that could be used topically and to targets directly the source of bleeding and reducing the local activation of the fibrinolytic process and consequently reducing the postoperative bleeding. Patients and Methods: A total of 70 patients underwent lung decortication surgery in Cardiothoracic Surgery Department at Tanta University Hospital from January 2015 to May 2017. Patients were randomly allocated into two groups, Group I (35 patients) receiving 3 g of tranexamic acid in 100 ml of saline solution and Group II (35 patients) receiving 100 ml of saline solution as placebo. At the end of the operation and before closing the chest, in both groups, drug or placebo solution was distributed locally all over the pleural cavity. Comparison between the groups was done regarding the amount of postoperative bleeding, postoperative hemoglobin in the first 24 and 48 h postoperatively, blood transfusion, Intensive Care Unit (ICU) stay, and hospital stay. Results: Both groups were comparable regarding demographic and surgical data. Group I patients had the significantly lesser amount of postoperative blood loss than Group II during the first postoperative 48 h, and hence, the need of postoperative blood transfusion was significantly lower in Group I with better postoperative hemoglobin level than Group II. However, there was no difference in overall ICU and hospital stay. Conclusion: The local intrapleural use of tranexamic acid after decortication surgery of the lung is safe and significantly reduces the amount of postoperative blood loss and in consequence reduces the amount of postoperative blood transfusion.

Sedation effects by dexmedetomidine versus propofol in decreasing duration of mechanical ventilation after open heart surgery.

OBJECTIVE: : The objective of this study was to compare the suitability (efficacy and safety) of dexmedetomidine versus propofol for patients admitted to the intensive care unit (ICU) after the cardiovascular surgery for the postoperative sedation before weaning from mechanical ventilation. BACKGROUND: Sedation is prescribed in patients admitted to the ICU after cardiovascular surgery to reduce the patient discomfort, ventilator asynchrony, to make mechanical ventilation tolerable, prevent accidental device removal, and to reduce metabolic demands during respiratory and hemodynamic instability. Careful drug selection for sedation by the ICU team, postcardiovascular surgery should be done so that patients can be easily weaned from mechanical ventilation after sedation is stopped to achieve a shorter duration of mechanical ventilation and decreased the length of stay in ICU. METHODS: A total of 50 patients admitted to the ICU after cardiovascular surgery, aged from 18 to 55 years and requiring mechanical ventilation on arrival to the ICU were enrolled in a prospective and comparative study. They were randomly divided into two groups as follows: Group D patients (n = 25) received dexmedetomidine in a maintenance infusion dose of 0.8 µg/kg/h and Group P patients (n = 25) received propofol in a maintenance infusion dose of 1.5 mg/kg/h. The patients were assessed for 12 h postoperatively, and dosing of the study drug was adjusted based on sedation assessment performed with the Richmond Agitation-Sedation Scale (RASS). The patients were required to be within the RASS target range of -2 to +1 at the time of study drug initiation. At every 4 h, the following information was recorded from each patient such as heart rate (HR), mean arterial pressure (MAP), arterial blood gases (ABG), tidal volume (TV), exhaled TV, maximum inspiratory pressure, respiratory rate and the rapid shallow breathing index, duration of mechanical ventilation, midazolam and fentanyl dose requirements, and financial costs. RESULTS: The study results showed no statistically significant difference between both groups with regard to age and body mass index. Group P patients were more associated with lower MAP and HR than Group D patients. There was no statistically significant difference between groups with regard to ABG findings, oxygenation, ventilation, and respiratory parameters. There was significant difference between both the groups in midazolam and fentanyl dose requirement and financial costs with a value of P < 0.05. CONCLUSION: Dexmedetomidine is safer and equally effective agent for the sedation of mechanically ventilated patients admitted to the ICU after cardiovascular surgery compared to the patients receiving propofol, with good hemodynamic stability, and equally rapid extubation time.

Infusion of low-dose vasopressin improves left ventricular function during separation from cardiopulmonary bypass: a double-blind randomized study.

We aimed to investigate whether low-dose vasopressin administered to patients undergoing coronary artery bypass grafting (CABG) surgery with preexisting mild to moderate systolic dysfunction can produce sustained improvement in cardiac function. This double-blind randomized study was conducted in a hospital where a single anesthetic and surgical team performed elective CABG. Twenty patients aged 32-61 years who underwent elective CABG between January 2007 and December 2007 were enrolled in this study. The patients randomly received either vasopressin 0.03 IU/min (Group A) or normal saline (Group B) in equal volume for 60 min after cardiopulmonary bypass (CPB). The cardiac output, cardiac index, stroke volume index, fractional area of contraction and systemic vascular resistance index were significantly higher in Group A than in Group B. Adrenaline (mean dose: 0.06 µg/kg x min-1) was required in seven patients from Group B but in none of the Group A patients on initial separation from CPB (P< 0.05). Of the 10 patients in Group B, five required phenylepherine to maintain the mean arterial pressure (MAP) >65 mmHg, whereas none of the Group A patients required phenylephrine for MAP regulation (P< 0.05). We conclude that Infusion of low-dose vasopressin for patients with mild to moderate left ventricular systolic dysfunction during separation from CPB is beneficial for the postoperative hemodynamic profile, reduces the catecholamine doses required and improves left ventricular systolic function.