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Oncolytic viruses represent a novel drug class in which native or modified viruses mediate tumor regression through selective replication within and lysis of tumor cells as well as induction of systemic antitumor immunity capable of eradicating tumor at distant, uninjected sites. Talimogene laherparepvec (TVEC) is a type I herpes simplex virus genetically modified to preferentially replicate in tumor cells, enhance antigen loading of MHC class I molecules and express granulocyte-macrophage colony-stimulating factor to increase tumor-antigen presentation by dendritic cells. It is presently the only oncolytic virus approved by the FDA with an indication for advanced melanoma based upon improved durable response rate in a randomized, phase III trial. Clinical trials are underway in melanoma investigating TVEC as neoadjuvant monotherapy and in combination with checkpoint inhibitors for unresectable disease as well as in an array of other malignancies. It is appropriate to review TVEC's biology mechanism of action, clinical indication and future directions as a prototype of the burgeoning class of oncolytic viruses.

Objective: Demonstrate that an endoscopic keyhole approach to the middle cranial fossa is technically feasible for repair of semicircular canal dehiscence., Study Design: Cadaveric technical feasibility/methods development study., Setting: Tertiary care military medical center., Patients: Three fresh cadaveric heads (six sides)., Intervention(s): Endoscopic minimally invasive approach to the middle cranial fossa using the Medtronic Fusion Guidance system., Main Outcome Measure(s): Ability to identify the surgical landmarks of the middle cranial fossa and successfully identify and instrument the superior semicircular canal., Results: In every attempt, the arcuate eminence was successfully identified under endoscopic visualization and with the assistance of surgical navigation. The superior semicircular canal was unroofed, and its location confirmed visually and with the navigation system. The opened canal was then plugged with bone wax, bone pate, and covered with fascia. The 15-mm burr hole craniotomy provided ample room for one working instrument and a 4-mm 0-degree endoscope., Conclusion: The endoscopic keyhole approach to superior semicircular canal dehiscence is technically feasible in a human cadaveric model. Further studies will determine 1) if this approach is possible and safe in vivo, 2) is associated with improved surgical outcomes, and 3) if surgical navigation aids in this approach.

There are only a few cases of prosthetic valve endocarditis (PVE) following transcatheter aortic valve implantation (TAVI) reported in the literature. Though not very frequent, this is a serious concern because patients are high risk for surgical aortic valve replacement (SAVR) by definition, and explanting the endocarditic prosthetic valve followed by SAVR increases risk even higher.

Pregnant and young mothers' stories often go untold within community social and health service policy, planning and practice. Consequently, there is a significant gap between young women's experiences of motherhood and current service provision. This study was undertaken in response to a paucity of observational and contextually rich research that explores young women's experiences of pregnancy and motherhood, including the role a community service played in scaffolding their motherhood journeys. Fundamental to this study's purpose was the premise that to improve planning and delivery of more appropriate services for this group, we need to listen, consult and consider what life is like for young mothers. The purpose of this paper is to describe the role a community service played in scaffolding young women's experiences as they transitioned to motherhood. Using a narrative approach, this study draws on data collected from contextual observations of 31 informants and 11 in-depth interviews over 7 months of fieldwork in 2010 at a community service in the Peel region of Western Australia. The integral role a community service played in the young women's transition to motherhood was analysed thematically and captured in three metaphorical themes, finding a circle of friends, weaving a tapestry and turning the page. The young women's storied experiences of motherhood present a strong argument for radical re-visioning of community and social health policy, practice and service delivery for young mothers. The findings revealed that judgement-free services that foster social and supportive relationships were integral in developing positive motherhood identities. The power of narrative and social learning when working with young mothers suggests that social models of health that foster a relational, narrative approach to practice are fundamental to young mothers finding their own voices and solutions and becoming active agents in re-authoring future narratives of hope, autonomy and agency., (© 2014 John Wiley & Sons Ltd.)

Background: Concern about the possible adverse effects of the cardiopulmonary bypass (CPB) pump and advances in retractors and operative techniques to access all coronary segments have resulted in increased interest in off-pump coronary artery bypass (OPCAB) procedures. Four of the Northern New England Cardiovascular Disease Study Group centers initiated OPCAB programs in 1998. We compared the preoperative risk profiles and in-hospital outcomes of patients done off-pump with those done by conventional coronary artery bypass (CCAB) with CPB., Methods: Between 1998 and 2000, 1,741 OPCAB and 6,126 CCAB procedures were performed at these four medical centers. Minimally invasive direct coronary artery bypass grafting procedures were excluded. Data were available for patient and disease risk factors, extent of coronary disease and adverse in-hospital outcomes., Results: The OPCAB and CCAB groups were somewhat different in their preoperative patient and disease characteristics. The OPCAB patients were more likely to be female and to have peripheral vascular disease. The CCAB patients were more likely to have an ejection fraction less than 0.40 and be urgent or emergent at operation. However, overall predicted risk of in-hospital mortality, based on preoperative factors, was similar in the OPCAB and CCAB groups; the mean predicted risk was 2.6% (p = 0.567). Crude rates of mortality (2.54% OPCAB versus 2.57%, CCAB), intraoperative or postoperative stroke (1.33% versus 1.82%), mediastinitis (1.10% versus 1.37%), and return to the operating room for bleeding (3.46% versus 2.93%) did not differ significantly. The OPCAB patients did have a statistically significant reduction in the need for intraoperative or postoperative intraaortic balloon pump support (2.31% versus 3.41%; p = 0.023) and in the incidence of postoperative atrial fibrillation (21.21% versus 26.31%; p < 0.001). Adjustment for preoperative risk factors and extent of coronary disease did not substantially change the crude results. Median postoperative length of stay was significantly shorter (5 days versus 6 days, p < 0.001) for OPCAB patients than for CCAB patients., Conclusions: This multicenter study showed that patients having OPCAB are not exposed to a greater risk of short-term adverse outcomes. These data also provided evidence that patients having OPCAB have significantly lower need for intraoperative or postoperative intraaortic balloon pump, lower rates of postoperative atrial fibrillation, and a shorter length of stay.

Primary carcinoid tumors of the mediastinum were described for the first time in 1972 as thymic carcinoids. Our experience with 16 patients who underwent diagnostic and surgical procedures at the Mayo Clinic is presented. All of these patients had mediastinal carcinoid. The surgical procedures included node biopsy, anterior mediastinotomy (Chamberlain), median sternotomy and posterior lateral thoracotomy. Complete resection was possible in 9 (56.3%) patients, 3 (18.7%) had partial removal (debulking), and 4 (25%) had diagnostic biopsies only. The operative morbidity was 25%. There were no postoperative deaths. In resectable patients, the average disease free interval was 45.7 months. Five year and ten year survival was 47% and 22%, respectively. Local or distant metastatic spread developed in all patients (100%). Mediastinal carcinoids are a separate entity from other thymic and mediastinal neoplasms. (We suggest that) Surgical excision may be possible earlier in the disease and radiation and chemotherapy are of doubtful value.

Herein we describe a case of pyopneumopericardium that resulted from formation of an acquired esophagopericardial fistula in a patient with silent, benign esophageal ulcer disease. Atypical features on initial examination suggested congestive heart failure or a pneumonic process (or both). The delayed development of pneumopericardium disclosed on a chest roentgenogram led to the clinical recognition of the esophagopericardial fistula. Subsequent emergent pericardiocentesis relieved cardiac tamponade and enabled us to diagnose pyopneumopericardium. A radiographic contrast study with use of meglumine diatrizoate revealed the site of the fistula in the midesophagus. The esophagopericardial fistula was surgically closed, and our patient had a good final result. Formation of an esophagopericardial fistula is a relatively uncommon finding; of the 60 previously reported cases, only 10 patients have survived. As illustrated in the current case, early diagnosis and treatment, including pericardial drainage and intense antibiotic therapy followed by a well-planned operative closure of the fistula, are paramount for the successful management of esophagopericardial fistulas.

During coronary artery bypass graft operations, the saphenous vein graft and native coronary arteries in 17 patients were examined with a 1.7 mm fiberoptic catheter to determine the feasibility of the procedure and its potential for clinical application. Good to excellent visualization in 10 of 11 proximal and 10 of 10 distal coronary anastomoses was obtained promptly and consistently. Good visualization of native coronary arteries was obtained in only six of 11 vessels. Three of three coronary arteries were visualized through the completed distal anastomosis, whereas only three of eight vessels could be visualized directly through the arteriotomy site before completion of the distal anastomosis. The image quality improved with operator experience. Vessel distention by cold crystalloid solution during catheter visualization was also important for obtaining better images. Limitations of the current "state of the art" fiberoptic catheters include the large size relative to the usual dimensions of the native coronary vessels, a lack of perfusion channel, and the absence of an angulation or guiding system. Potentially, angioscopic catheters may be useful as an instructional aid during bypass operations or as a diagnostic tool in monitoring arterial status after thrombolytic intervention, balloon angioplasty, or laser therapy.

Placental transfer and fetal toxicity of pesticides have been documented in normotensive rats but no reports appear in the literature regarding the susceptibility of spontaneously hypertensive (SHR) perinates to pesticide challenge. This report describes the effects of prolonged parathion exposure to perinatal rats born to hypertensive dams. Ninety day old, spontaneously hypertensive (WKY strain) male and female rats were bred and vaginal plugs were used to determine that copulation had occurred. Parathion (0.01, 0.10 and 1.00 mg/kg) suspended in peanut oil was administered daily to the dam via oral intubation from day one of gestation to day fifteen of lactation, a total of thirty-seven days. On day twenty-four post partum the perinates were examined. Male and female SHR perinates exhibited a significant reduction in plasma cholinesterase at the 1.00 mg/kg dose level. Changes in relative organ weights, hematological parameters and serum enzymes were found. Heart rate was significantly reduced at the 0.01 mg/kg and 0.10 mg/kg dose levels. The results of this study indicate that exposure of SHR dams to parathion during gestation and lactation resulted in toxicological effects in the perinate basically similar to those seen in normotensive perinates.

Proximal cervical esophageal diversion is occasionally employed in the management of distal esophageal perforation. However, subsequent esophageal reconstruction can pose a formidable surgical challenge. The DeBakey femoral tunneling device has proven helpful in identifying the distal defunctionalized segment of esophagus during certain types of reconstruction. We describe the use of this instrument to reestablish esophageal continuity in two instances.