Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP).

Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a new treatment approach for CUP in a personalized fashion using targeted agents. We analyzed the mutation and copy number alterations profile of 1709 CUP samples deposited in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) cohort and explored potentially druggable mutations. We identified 52 significant mutated genes (SMGs) among CUP samples, in which 13 (25%) of SMGs were potentially targetable with either drugs are approved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, using pan-cancer analysis, we found similar variants of TERT promoter in CUP and NSCLC samples, suggesting that these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, the mutation profiling analysis of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner

Does B-type natriuretic peptide level predict outcome after arterial switch operation ?

Evaluation the predictive value of perioperative Plasma B-type natriuretic peptide level in arterial switch operation. Plasma B-type natriuretic peptide level was measured before and and 24 hours after surgery in 29 patients with arterial switch operation. We evaluated 29 patients (22 male,76,7 female 24) with mean age 67.93±84.09 days (range 6 days to 14months).The mean of BNP level before surgery was 7989.96±9691.94 and increased after surgery to 22391.35±11898.67 and difference between two groups was significant (P=0.003).In linear regression test the BNP did not correlate with sex(r=0.33, P=0.085) and age(r=0.14,P=0.45). Furthermore, BNP did not correlate with duration of mechanical ventilation (r=0.132,P=0.53), ICU stay (r=0.137,P=0.52) and with lactate level (r=0.41,P=0.054)after operation. During the study 4 patients(13.8) died and the mean of BNP 24h after operation among them was 35000.00±00.00.using chai-square and fisher exact test the correlation between BNP and death was significant(P=0.001). We implied that BNP level increased 24 hours after arterial switch operation, moreover we denoted it correlated well with the death rate and an increase in B-type natriuretic peptide 24 hours after surgery predicts poor postoperative outcome. However it did not correlate with duration of mechanical ventilation, ICU stay and lactate level in this patients

Prediction of the treatment response in ovarian cancer: a ctDNA approach.

Ovarian cancer is the eighth most commonly occurring cancer in women. Clinically, the limitation of conventional screening and monitoring approaches inhibits high throughput analysis of the tumor molecular markers toward prediction of treatment response. Recently, analysis of liquid biopsies including circulating tumor DNA (ctDNA) open new way toward cancer diagnosis and treatment in a personalized manner in various types of solid tumors. In the case of ovarian carcinoma, growing pre-clinical and clinical studies underscored promising application of ctDNA in diagnosis, prognosis, and prediction of treatment response. In this review, we accumulate and highlight recent molecular findings of ctDNA analysis and its associations with treatment response and patient outcome. Additionally, we discussed the potential application of ctDNA in the personalized treatment of ovarian carcinoma. ctDNA-monitoring usage during the ovarian cancer treatments procedures

Impact of vitamin C supplementation on post-cardiac surgery ICU and hospital length of stay

Background: Prolonged intensive care unit (ICU) and hospital stay after cardiac surgery is vitally important and is influenced by both intraoperative and postoperative factors.Objectives: This randomized clinical trial study was designed to assess whether vitamin C supplementation could reduce the length of ICU and hospital stay in post-cardiac surgery patients.Patients and Methods: Two hundred and ninety patients scheduled for adult cardiac surgery including coronary, valve and congenital operations were randomized into two groups: an intervention group, who received 2 g of vitamin C (ascorbic acid) intravenously, immediately before surgery in the operating theatre, followed by 1 g daily oral doses for the first 4 postoperative days; and a placebo group,who received an equal number of identical tablets in the same shape and size. Results: Hospital length of stay was significantly different between the two groups (10.17 ± 4.63 days in the intervention group vs. 12 ± 4.51 days in the placebo group; P = 0.01), while there was no significant difference in the ICU stay between the groups (3.42 ± 1.06 days in intervention group vs. 3.43 ± 1.09 days in the placebo group; P = 0.88). There were significant differences in the intubation time and the drainage volume in the ICU and the first 24 postoperative hours between the two groups (P for both = 0.003). Conclusions: Vitamin C can decrease the length of hospital stay, drainage volume in the ICU and in the first 24 postoperative hours, intubation time and some complications in patients after cardiac surgery; perhaps by decreasing inflammatory factors. Background: Prolonged intensive care unit (ICU) and hospital stay after cardiac surgery is vitally important and is influenced by both intraoperative and postoperative factors.Objectives: This randomized clinical trial study was designed to assess whether vitamin C supplementation could reduce the length of ICU and hospital stay in post-cardiac surgery patients.Patients and Methods: Two hundred and ninety patients scheduled for adult cardiac surgery including coronary, valve and congenital operations were randomized into two groups: an intervention group, who received 2 g of vitamin C (ascorbic acid) intravenously, immediately before surgery in the operating theatre, followed by 1 g daily oral doses for the first 4 postoperative days; and a placebo group,who received an equal number of identical tablets in the same shape and size. Results: Hospital length of stay was significantly different between the two groups (10.17 ± 4.63 days in the intervention group vs. 12 ± 4.51 days in the placebo group; P = 0.01), while there was no significant difference in the ICU stay between the groups (3.42 ± 1.06 days in intervention group vs. 3.43 ± 1.09 days in the placebo group; P = 0.88). There were significant differences in the intubation time and the drainage volume in the ICU and the first 24 postoperative hours between the two groups (P for both = 0.003). Conclusions: Vitamin C can decrease the length of hospital stay, drainage volume in the ICU and in the first 24 postoperative hours, intubation time and some complications in patients after cardiac surgery; perhaps by decreasing inflammatory factors. © 2015, Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM)

A Comparison Between the Hemodynamic Effects of Cisatracurium and Atracurium in Patient with Low Function of Left Ventricle who are Candidate for Open Heart Surgery

BACKGROUND: The need for muscle relaxants in general anesthesia in different surgeries including cardiac surgeries, and the type of relaxant to be used considering its different hemodynamic effects on patients with heart disease can be of considerable importance. In this study, the hemodynamic effects of two muscle relaxants, Cisatracurium and Atracurium in patients whit low function of left ventricle who are candidate for open heart surgery have been considered. METHOD: This study has been designed as a randomized prospective double-blind clinical trial. The target population included all adult patients with heart disease whose ejection fraction reported by echocardiography or cardiac catheterization was 35 or less before the surgery, and were candidate for open heart surgery in Shahid Rajaei Heart Center. Taking into account the inclusion and exclusion criteria, the patients were randomly placed in two groups of 30 people each. In the induction stage, all the patients received midazolam, etomidate, and one of the considered muscle relaxant, either 0.2 mg/kg of cisatracurium or 0.5mg/kg of Atracurium within one minute. In the maintenance stage of anesthesia, the patients were administered by infusion of midazolam, sufentanil and the same muscle relaxant used in the induction stage. The hemodynamic indexes were recorded and evaluated in different stages of anesthesia and surgery as well as prior to transfer to ICU. RESULTS: In regard with descriptive indexes (age and sex distributions, premedication with cardiac drugs, ejection fraction before surgery, basic disease) there was no statistically significant difference between the groups. CONCLUSIONS: The significant difference of hemodynamic indexes between the two groups of this study, and the need for hemodynamic stability in all stages of surgery for patients with low function of left ventricle who are candidate for open heart surgery, proves that administering Cisatracurium as the muscle relaxant is advantageous and better

Comparison of two pain assessment tools, �facial expression� and �critical care pain observation tool� in intubated patients after cardiac surgery

Background: Critical-care patients are at higher risk of untreated pain, because they are often unable to communicate owing to altered mental status, tracheal intubation and sedation. Objectives: This study compared two pain assessment tools on tracheal intubated critically ill patients in a cardiac post-anesthesia care unit, who were unable to communicate verbally. The studied tools were �critical-care pain observation tool (CPOT)� and �facial expression (FE)�. Patients and Methods: This was a prospective study based on diagnostic test evaluation. A sample of 91 intubated patients was selected from cardiac post-anesthesia care unit. Collected data were demographic characteristics, vital signs, FE and CPOT tools� scale. Pain was assessed with CPOT and FE scores five times. The first assessment was performed in at least 3 hours after admission of patients to ICU. Then, the pain intensity was reassessed every 30 minutes. In addition, blood pressure, heart rate, respiratory rate and oxygen saturation were measured simultaneously. Results: At the first period, the frequency of �severe� pain intensity using the CPOT was 58.2 and with the FE tool was 67 (P = 0.001). Both tools demonstrated reduction in severity of pain on second and third assessment times. Significantly increasing level of pain and blood pressure due to nursing painful procedures (endo-tracheal suctioning, changing patient�s position, etc.), were obtained by CPOT in fourth assessment. FE was not able to detect such important findings (κ = 0.249). In the fifth step, pain intensity was reduced. The most agreement between the two tools was observed when the reported pain was �severe� (κ = 0.787, P < 0.001) and �mild� (κ = 0.851, P < 0.001). Conclusions: The sensitivity of CPOT was higher for detection and evaluation of pain in intubated postoperative patients compared with �Facial Expression�. Best agreement between these tools was observed in two extremes of pain intensity. © 2016, Iranian Society of Regional Anesthesia and Pain Medicine (ISRAPM)

Atherosclerosis and autoimmunity: a growing relationship

Atherosclerosis is regarded as one of the leading causes of mortality and morbidity in the world. Nowadays, it seems that atherosclerosis cannot be defined merely through the Framingham traditional risk factors and that autoimmunity settings exert a remarkable role in its mechanobiology. Individuals with autoimmune disorders show enhanced occurrence of cardiovascular complications and subclinical atherosclerosis. The mechanisms underlying the atherosclerosis in disorders like rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis and Sjögren's syndrome, seem to be the classical risk factors. However, chronic inflammatory processes and abnormal immune function may also be involved in atherosclerosis development. Autoantigens, autoantibodies, infectious agents and pro-inflammatory mediators exert a role in that process. Being armed with the mechanisms underlying autoimmunity in the etiopathogenesis of atherosclerosis in rheumatic autoimmune disorders and the shared etiologic pathway may result in substantial developing therapeutics for these patients. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Lt

Effects of Dexmedetomidine on surgical stress responses at patients under CABG

Cardiopulmonary bypass (CPB) surgery with extracorporeal circulation produce changes in the immune system and plasma levels of inflammatory cytokines. we hypothesize that Dexmedetomidine as an adjuvant , modulates the inflammatory response after CABG. In a prospective, randomized, blind study, 31 patients were assigned to Dexmedetomidine (Dex) group and compared with control group of 30 patients. Dex was administered at a loading dose of 0.5 μg/kg for 10 min , followed by a continuous infusion of 0.5 μg/kg per hour until the completion of CABG with CPB . The endpoints used to assess inflammatory responses to mini - CPB were plasma tumor necrosis factor (TNF) - � , interleukin (IL - 6 ) and interleukin ( IL - 10) levels. The inflammatory markers (IL - 6 , IL - 10 , TNF - � ) were determined after Dex administration , before CPB and 24 hours after admission to ICU. Biochemical factors including glucose , creatinine , lactate , BUN, AST , ALT , LDH were determined before CPB, immediately after entering the ICU , 24 hr , 48 hr and 72 hr post admission to ICU. Hemodynamic variables were also determined. Dex group was associated with a significant reduction in urea and creatinine. There were no significant differences in glucose, lactate, liver enzymes, LDH , IL - 6, IL - 10 and hemodynamic variables. In contrast, the surgery - induced increase in TNF - � levels in the Dex group was significantly higher compared with the control group

Atherosclerosis and autoimmunity: a growing relationship

Atherosclerosis is regarded as one of the leading causes of mortality and morbidity in the world. Nowadays, it seems that atherosclerosis cannot be defined merely through the Framingham traditional risk factors and that autoimmunity settings exert a remarkable role in its mechanobiology. Individuals with autoimmune disorders show enhanced occurrence of cardiovascular complications and subclinical atherosclerosis. The mechanisms underlying the atherosclerosis in disorders like rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, systemic sclerosis and Sjögren's syndrome, seem to be the classical risk factors. However, chronic inflammatory processes and abnormal immune function may also be involved in atherosclerosis development. Autoantigens, autoantibodies, infectious agents and pro-inflammatory mediators exert a role in that process. Being armed with the mechanisms underlying autoimmunity in the etiopathogenesis of atherosclerosis in rheumatic autoimmune disorders and the shared etiologic pathway may result in substantial developing therapeutics for these patients. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Lt

Relationship between maximum clot firmness in ROTEM® and postoperative bleeding after coronary artery bypass graft surgery in patients using clopidogrel

Background: The aim of the present study was to investigate the relationship between maximum clot firmness (MCF) in rotational thromboelastometry (ROTEM®) and postoperative bleeding in patients on clopidogrel after emergency coronary artery bypass graft surgery (CABG). Methods: This observational study recruited 60 patients posted for emergency CABG following unsuccessful primary percutaneous coronary intervention (PCI) while on 600 mg of clopidogrel. The study population was divided into 2 groups on the basis of their MCF in the extrinsically activated thromboelastometric (EXTEM) component of the (preoperative) ROTEM® test: patients with MCF &lt;50 mm (n = 16) and those with MCF �50 mm (n = 44). Postoperative chest tube drainage amount, need for blood product transfusion, postoperative complications, and duration of mechanical ventilation after CABG were recorded. Results: No significant differences were observed between the two groups regarding duration of surgery, cardiopulmonary bypass, and aortic cross-clamp time. Chest tube drainage at 6, 12, and 24 h after Intensive Care Unit admission were significantly higher in the patients with MCF below 50 mm. The need for blood product transfusion was higher in the group with MCF &lt;50 mm. In patients who experienced postoperative bleeding of 1000 mL or more, the ROTEM® parameters of INTEM (Intrinsically activated thromboelastomery) and MCF, EXTEM and MCF, and HEPTEM (INTEM assay performed in the presence of heparinase) MCF (but not FIBTEM (Thromboelastometric assay for the fibrin part of the clot) values) were significantly lower than those with postoperative bleeding &lt;1000 mL (P � 0.05). Conclusions: When platelet aggregometry is not available, the ROTEM® test could be useful for the prediction of increased risk bleeding after emergency CABG in patients who have received a loading dose of clopidogrel. © 2018 Annals of Cardiac Anaesthesia | Published by Wolters Kluwer - Medknow