Transfection of hypoxia-inducible factor-1α mRNA upregulates the expression of genes encoding angiogenic growth factors.

Hypoxia-Inducible Factor-1α (HIF-1α) has presented a new direction for ischemic preconditioning of surgical flaps to promote their survival. In a previous study, we demonstrated the effectiveness of HIF-1a DNA plasmids in this application. In this study, to avoid complications associated with plasmid use, we sought to express HIF-1α through mRNA transfection and determine its biological activity by measuring the upregulation of downstream angiogenic genes. We transfected six different HIF-1a mRNAs-one predominant, three variant, and two novel mutant isoforms-into primary human dermal fibroblasts using Lipofectamine, and assessed mRNA levels using RT-qPCR. At all time points examined after transfection (3, 6, and 10 h), the levels of HIF-1α transcript were significantly higher in all HIF-1α transfected cells relative to the control (all p < 0.05, unpaired Student's T-test). Importantly, the expression of HIF-1α transcription response genes (VEGF, ANG-1, PGF, FLT1, and EDN1) was significantly higher in the cells transfected with all isoforms than with the control at six and/or ten hours post-transfection. All isoforms were transfected successfully into human fibroblast cells, resulting in the rapid upregulation of all five downstream angiogenic targets tested. These findings support the potential use of HIF-1α mRNA for protecting ischemic dermal flaps.

Induced Pluripotent Stem Cell-Derived Extracellular Vesicles Promote Wound Repair in a Diabetic Mouse Model via an Anti-Inflammatory Immunomodulatory Mechanism.

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been explored in clinical trials for treatment of diseases with complex pathophysiologies. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, it is initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, it is found that their vascularization bioactivity is similar and their anti-inflammatory bioactivity is superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial is employed. In this in vivo model, iPSC EVs more effectively mediate inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

Induced pluripotent stem cell-derived extracellular vesicles promote wound repair in a diabetic mouse model via an anti-inflammatory immunomodulatory mechanism.

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have recently been widely explored in clinical trials for treatment of diseases with complex pathophysiology. However, production of MSC EVs is currently hampered by donor-specific characteristics and limited ex vivo expansion capabilities before decreased potency, thus restricting their potential as a scalable and reproducible therapeutic. Induced pluripotent stem cells (iPSCs) represent a self-renewing source for obtaining differentiated iPSC-derived MSCs (iMSCs), circumventing both scalability and donor variability concerns for therapeutic EV production. Thus, we initially sought to evaluate the therapeutic potential of iMSC EVs. Interestingly, while utilizing undifferentiated iPSC EVs as a control, we found that their vascularization bioactivity was similar and their anti-inflammatory bioactivity was superior to donor-matched iMSC EVs in cell-based assays. To supplement this initial in vitro bioactivity screen, we employed a diabetic wound healing mouse model where both the pro-vascularization and anti-inflammatory activity of these EVs would be beneficial. In this in vivo model, iPSC EVs more effectively mediated inflammation resolution within the wound bed. Combined with the lack of additional differentiation steps required for iMSC generation, these results support the use of undifferentiated iPSCs as a source for therapeutic EV production with respect to both scalability and efficacy.

Pioneering use of genetic analysis for CDH1 to identify candidates for prophylactic total gastrectomy to prevent hereditary diffuse gastric cancer.

Worldwide, gastric cancer results in significant morbidity and mortality. Ten per cent of patients with gastric cancer have a strong family history of the disease. CDH1 (E-cadherin) has been identified as a key gene whose mutation leads to hereditary diffuse gastric cancer. We overviewed 33 articles with prophylactic total gastrectomy and assessed the outcomes and benefits. Families with mutations in CDH1 may benefit from early prophylactic total gastrectomy. Dr Mark Duncan has applied his experience as a high-volume gastric cancer surgeon to treat not only individual patients, but several generations of patients within a family. This use of prophylactic total gastrectomy is well tolerated by patients and prevents the future development of gastric cancer.

Primary Thoracic Wall Hydatid Cyst Extended to the Abdominal wall: A Case Report.

Hydatid disease (HD) is an infectious disease caused by echinococcosis. Hydatid cyst (HC) most commonly invades the liver (60-70%) and the lungs (20-25%). However, other parts of the body and even unusual locations can be infected, mimicking a benign lesion that could be easily missed. Primary HC of the chest wall is extremely rare, even in countries where echinococcosis is endemic. We herein present a case of a 40-year-old man with a right-sided growing thoracic wall mass. The patient did not present the relevant history (living in rural areas or being in contact with farm animals) and the serological examination with the indirect hemagglutination test was negative. During surgery, a cystic mass between the eleventh and twelfth ribs was observed. The thoracic wall mass extended to the posterior abdominal wall and was entirely extrapulmonary and extraperitoneal. All cystic structures of the thoracic wall and intrathoracic region were removed, and the primary defect was reconstructed. In endemic areas such as Iran, HD should be considered in the differential diagnosis of mass lesions located in the chest wall or other parts of the body, even without the relevant history or serologic evidence.

Effect of Hyperoxygenation During Surgery on Surgical Site Infection in Colorectal Surgery.

PURPOSE: Despite the use of different surgical methods, surgical site infection is still an important cause of mortality and morbidity in patients and imposes a considerable cost on the healthcare system. Administration of supplemental oxygen during surgery has been reported to reduce surgical site infection (SSI); however, that result is still controversial. This study was performed to evaluate the effect of hyperoxygenation during colorectal surgery on the incidence of wound infection. METHODS: This study was a prospective double-blind case-control study. The main aim of the study was to evaluate the effect of hyperoxygenation during colorectal surgery on the incidence of SSI. Also, secondary outcomes, such as atelectasis, pneumonia, respiratory failure, length of hospital stay, and required hospitalization in the intensive care unit were evaluated. RESULTS: SSI was recorded in 2 patients (2 of 40, 5%) in the hyperoxygenation group (FiO2 80%) and 6 patients (6 of 40, 15%) in the control group (FiO2 30%) (P < 0.05). Time of hospitalization was 6 ± 6.4 days in the hyperoxygenation group and 9.2 ± 2.4 days in the control group (P < 0.05). CONCLUSION: This study showed a positive effect of hyperoxygenation in reducing SSI in colorectal surgery, especially surgery in an emergency setting. When the low risk, low cost, and effectiveness of this method in patients undergoing a laparotomy are considered, it is recommended for all patients undergoing colorectal surgery.

Laparoscopic Repair of Morgagni Hernia: Three-Case Presentation and the Literature.

Introduction. Morgagni hernia is a rare form of congenital diaphragmatic hernia. Case Presentation. We present three cases of Morgagni hernia with GI symptoms treated by laparoscopic surgery. Discussion. Hernial sac was excised in two cases and left in situ in one case. There was no recurrence in symptoms after 30 months from surgery.

Clinical presentation of coronary arteriovenous fistula according to age and anatomic orientation.

BACKGROUND: Coronary arteriovenous fistulas (CAVFs) are direct connections from one or more coronary arteries to cardiac chambers or a large vessel. They are mostly of congenital origin. The aim of this study was to describe clinical presentation and also delineate the course and management of CAVF. METHODS: Clinical data, chest x-rays, echocardiographic and angiographic evaluation of 40 patients with congenital CAVF during 1990 to 2008 were reviewed retrospectively. RESULTS: Seventeen patients were ≤ 20 years old (42.5%) were mostly asymptomatic, and twenty tree cases were older than 20 years old (57.5%), mostly symptomatic (P<0.05). Twenty one (52.5%) patients had pure CAVF and nineteen (47.5%) patients with associated intarcardiac congenital heart disease (15%) or acquired valvular and coronary arteries diseases (32.5%). CAVFs mostly originated from left anterior descending artery (LAD) (42.5%) and mostly drained into the main pulmonary artery (MPA) (35 %). Twenty-four patients underwent CAVF surgical ligation. From twenty-one patients with pure CAVF, eight (38%) patients were complicated by congestive heart failure and aneurism formation of fistula. CONCLUSION: Unlike some previous reports, in our study, the most prevalent origin site for CAVFs was the left anterior descending (LAD). Most patients with CAVFs especially those who went first diagnosed before 20 years old were asymptomatic. On the other hand, as the continuous murmur is not always detected in children or infants, consequently, cases of spontaneous closure may remain undetected. All symptomatic and asymptomatic patients with moderate to severe shunting should be operated on and minimal morbidity and good surgical results could be expected.

Evaluations of erectile dysfunction before and after on-pump coronary artery bypass graft surgery.

BACKGROUND: Erectile dysfunction (ED) is common in cardiovascular disease (CVD) and indicates a complication of coronary artery bypass graft surgery (CABG). This study was designed to evaluate the status of erectile dysfunction in patients with CAD before and after CABG surgery. METHODS: We designed a prospective cohort study on male patients candidates for elective on-pump CABG between June 2006 to October 2012 in 3 hospitals in Sari, Iran (Fatemeh Zahra, Shafa and Nime-Shaban Hospitals). Patient's primary data were collected based on the International Index of Erectile Function questionnaire (IIEF-5) at baseline 6 months after surgery. The severity of dysfunction was categorized as, normal, mild to moderate and moderate to severe based on IIEF score. RESULTS: Four hundred twenty-six male patients with mean age of 58.69±12.49 years participated in this study. 166 patients had DM (38.96%) 230 patients had hypertension (54%). 307 patients had three-vessel impairment (72.07%) and 119 patients with one or two vessel impairment (27.93%). The 15.02%, 18.07%, 23%, 31.92% and 11.97%, at baseline changed to 16.90%, 19.95%, 23.71%, 32.22% and 8.21%, at endpoint (P=0.01). Also, the mean±SD of IIEF-5 score before and after surgery was 13.95±5.44 and 14.20±5.69, respectively (P=0.001). CONCLUSION: The result of our study shows that on-pump CABG surgery has a positive effect on the improvement of erectile dysfunction 6 months after surgery.

Papillary fibroelastoma of a mitral valve chordae, presenting with atypical chest pain and palpitation: A case report and the literature.

BACKGROUND: Primary intra cardiac tumors are rare. In this article, we present papillary fibroelastoma of mitral valve chordae. CASE PRESENTATION: A 35-year old man presented with atypical chest pain and palpitation. Physical examination and electrocardiogram were normal. Transesophageal echocardiography (TEE) revealed a mass of 1015 mm attached to chordae of anteromedial papillary muscle of mitral valve. The tumor was completely resected and the mitral valve chordae tendineae was preserved successfully. The pathological diagnosis was papillary fibroelastoma. CONCLUSION: In any patient with atypical chest pain and palpitation, valvular tumor should be considered in differential diagnosis.

Echocardiographic Evaluation of the Effects of a Single Bolus of Erythropoietin on Reducing Ischemia-Reperfusion Injuries during Coronary Artery Bypass Graft Surgery; A Randomized, Double-Blind, Placebo-Control Study.

BACKGROUND: Erythropoietin (EPO) is known as a regulating hormone for the production of red blood cells, called erythropoiesis. Some studies have shown that EPO exerts some non-hematopoietic protective effects on ischemia-reperfusion injuries in myocytes. Using echocardiography, we evaluated the effect of EPO infusion on reducing ischemia-reperfusion injuries and improvement of the cardiac function shortly after coronary artery bypass graft surgery (CABG). METHODS: Forty-three patients were recruited in this study and randomly divided into two groups: the EPO group, receiving standard medication and CABG surgery plus EPO (700 IU/kg), and the control group, receiving standard medication and CABG surgery plus normal saline (10 cc) as placebo. The cardiac function was assessed through echocardiography before as well as at 4 and 30 days after CABG. RESULTS: Echocardiography indicated that the ejection fraction had no differences between the EPO and control groups at 4 days (47.05±6.29 vs. 45.90±4.97; P=0.334) and 30 days after surgery (47.27±28 vs. 46.62±5.7; P=0.69). There were no differences between the EPO and control groups in the wall motion score index at 4 (P=0.83) and 30 days after surgery (P=0.902). In the EPO group, there was a reduction in left ventricular end-systolic and end-diastolic diameters (LVESD and LVEDD, respectively), as compared to the control group. CONCLUSION: Our results indicated that perioperative exogenous EPO infusion could not improve the ventricular function and wall motion index in the immediate post-CABG weeks. Nevertheless, a reduction in LVEDD and LVESD at 4 days and 30 days after CABG in the EPO group, by comparison with the control group, suggested that EPO correlated with a reduction in the remodeling of myocytes and reperfusion injuries early after CABG. TRIAL REGISTRATION NUMBER: 138809102799N1.

Williams-Beuren's Syndrome: A Case Report.

Williams-Beuren syndrome is a rare familial multisystem disorder occurring in 1 per 20,000 live births. It is characterized by congenital heart defects (CHD), skeletal and renal anomalies, cognitive disorder, social personality disorder and dysmorphic facies. We present a case of Williams syndrome that presented to us with heart murmur and cognitive problem. A 5-year-old girl referred to pediatric cardiologist because of heart murmurs. She had a systolic murmur (2-3/6) in right upper sternal border with radiation to right cervical region. She also had a bulge forehead. Angiography showed mild supra valvular aortic stenosis and mild multiple peripheral pulmonary stenosis. Fluorescent in situ hybridization (FISH) was performed and the result was: 46.XX, ish del (7q11.2) (ELN X1) (7q22 X2) ELN deletion compatible with Williams syndrome. Peripheral pulmonary artery stenosis is associated with Noonan syndrome, Alagille syndrome, Cutis laxa, Ehler-Danlos syndrome, and Silver-Russel syndrome. The patient had peripheral pulmonary artery stenosis, but no other signs of these syndromes were present, and also she had a supravalvular aortic stenosis which was not seen in other syndromes except Williams syndrome. Conclusion. According to primary symptoms, paraclinical and clinical finding such as dysmorphic facies, cognitive disorder and congenital heart defect, Williams syndrome was the first diagnosis. We suggest a more attention for evaluating heart murmur in childhood period, especially when the patient has abnormal facial features or mental problem.

The successful withdrawal of a migrated central venous catheter.

BACKGROUND: Central venous catheters (CVCs) have been used widely in clinics. These catheters are also recommended for children and infants receiving chemotherapy and total parenteral nutrition (TPN) and etc. In this paper, we present migrated fractured control line of the heart of a girl. CASE PRESENTATION: A 2.5 year old girl with migrated of the fractured central line into the heart. In the catheterization laboratory, first we placed a long sheath (8 F) into the inferior vena cava via femoral vein and then trapped the foreign body by pigtail catheter and wire 0.035 inch and pulled it down to make its proximal free. After that, we snared the catheter by snare-catheter and pulled it into the femoral vein, and then the cardiac surgeon bridged it out by cut-down successfully. CONCLUSION: A rare complication in the use of central catheters is fraction and cardiac embolization. We offer gentle bringing out of the catheter lines under fluoroscopy guide in all of the cases, if this is technically possible and safe.