Citations

Background While clinical and angiographic risk factors for intracranial aneurysm instability are well established, it is reasonable to postulate that intra-aneurysmal hemodynamics also have a role in aneurysm instability. Objective To identify hemodynamic characteristics that differ between radiologically unstable and stable unruptured intracranial aneurysms. Materials and methods 12 pairs of unruptured intracranial aneurysms with a 3D rotational angiographic set of images and followed up longitudinally without treatment were studied. Each pair consisted of one stable aneurysm (no change on serial imaging) and one unstable aneurysm (demonstrated growth of at least 1 mm diameter or ruptured during follow-up) of matching size (within 10%) and locations. Patient-specific computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups using the paired Wilcoxon test. Results The area of the aneurysm under low wall shear stress (low shear stress area (LSA)) was 2.26 times larger in unstable aneurysms than in stable aneurysms (p=0.0499). The mean aneurysm vorticity was smaller by a factor of 0.57 in unstable aneurysms compared with stable aneurysms (p=0.0499). No statistically significant differences in geometric variables or shape indices were found. Conclusions This pilot study suggests there may be hemodynamic differences between unstable and stable unruptured cerebral aneurysms. In particular, the area under low wall shear stress was larger in unstable aneurysms. These findings should be considered tentative until confirmed by future larger studies.

ABSTRACT Introduction Penile prosthesis implantation has emerged as a definitive treatment to restore sexual function to the motivated man with erectile dysfunction. Substantial improvements in the design of inflatable devices have been made since they first became available more than four decades ago. Aim To review the history of the penile prosthesis, the indications, preoperative evaluation, and patient and partner satisfaction. The current approaches to addressing intra- and postoperative complications, provide an understanding of prosthesis infection, and placement of these devices will be reviewed. Methods A committee of worldwide experts in this field was assembled during the 2015 International Consultation on Sexual Medicine (ICSM) and performed a systematic review of the peer-reviewed published medical literature pertaining to penile prosthesis. Particular attention was given to higher level trials when available. Recommendations are based upon the Oxford Criteria. Main Outcome Measures Unfortunately there is limited level 1 and 2 evidence, and where expert opinion was utilized, the decision was unanimous within the committee with a goal of presenting a clinically relevant guideline pertaining to penile prostheses. Results Penile prosthesis has undergone an evolution over the past 40 years resulting in a more effective and reliable treatment for advanced erectile dysfunction not responding to less invasive methods including oral treatment with PDE5 inhibitors, vacuum erection device, and intracorporal injection therapy. It should be considered an appropriate treatment option for the man who wishes to restore erectile function and who understands the potential risk of mechanical failure and infection, both of which are less common now as a result of improvements made in device design as well as surgical protocols adhered to in the operating room. Patients must be clearly informed of the risks associated with penile prosthesis including mechanical failure, infection, shortening of the penis, change in sensation and configuration of the penis, as well as injury to local structures. Intraoperative complications are unusual but do occur and can usually be addressed intraoperatively to allow placement of the device at the time of initial surgery. Postoperative complications may also be addressed when they occur but may require more advanced reconstructive surgical techniques. Men with Peyronie's disease, corporal fibrosis due to infection, trauma, prior prosthesis explantation, priapism, and men who have undergone construction of a neophallus may require additional advanced maneuvers to obtain optimum results with a penile prosthesis. Conclusion Penile prosthesis remains as an important, viable, and effective treatment for male erectile dysfunction that does not respond to other less invasive approaches or when these approaches are contraindicated or not acceptable to the patient. These devices provide the patient with the ability to engage in penetrative sexual activity without interfering with urination, ejaculation, sensation, or orgasm. Although mechanical failure can occur, the current devices are more reliable as a result of design modifications. Infection remains the most dreaded complication but since the introduction of antibiotic and hydrophilic coatings, infection is less common. Overall, patient and partner satisfaction appear to be reasonably high when a penile prosthesis is used to restore erectile function.

Key Points HERC4 is the first identified ubiquitin ligase that mediates c-Maf ubiquitination and degradation. HERC4 suppresses MM cell proliferation and delays MM tumor growth.

ABSTRACTPrior studies have highlighted disparities in cardiac lifesaving procedure utilization, particularly among women and in minorities. Although there has been a significant increase in implantable cardioverter‐defibrillator (ICD) insertion, socioeconomic disparities still exist in the trend of ICD utilization. With the use of the Nationwide Inpatient Sample from 2003 through 2011, we identified subjects with ICD insertion (procedure code 37.94) and cardiac resynchronization defibrillator (procedure code 00.50, 00.51) as codified by the International Classification of Diseases, Ninth Revision, Clinical Modification. Overall, 1 020 076 ICDs were implanted in the United States from 2003 to 2011. We observed an initial increase in ICD utilization by 51%, from 95 062 in 2003 to 143 262 in 2006, followed by a more recent decline. The majority of ICDs were implanted in men age ≥65 years. Implantation of ICDs was 2.5× more common in men than in women (402 per million vs 163 per million). Approximately 95% of the ICDs were implanted in insured patients, and 5% were used in the uninsured population. There has been a significant increase in ICD implantation in blacks, from 162 per million in 2003 to 291 per million in 2011. We found a significant difference in the volume of ICD implants between the insured and the uninsured patient populations. Racial disparities have narrowed significantly in comparison with those noted in earlier studies and are now more reflective of the population demographics at large. On the other hand, significant gender disparities continue to exist.

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell‐derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti‐tumour therapy, (b) pathogen vaccination, (c) immune‐modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV‐based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV‐based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME‐HaD), summarize recent developments and the current knowledge of EV‐based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.