Organ-preference of metastasis

Summary The initial, site-specific colonization of secondary organs by blood-borne cancer cells appears to be mediated by endothelial cell adhesion molecules. These molecules are part of the organ-specific microvascular phenotype and are regulated through complex interactions of the endothelium with the extracellular matrix (e.g., distinct matrix macromolecules and growth factors). They are inducedin vitro by growing unspecific (large vessel) endothelial cells on extracts of organ-specific biomatrices. In many respects, these molecules are similar to the various classes of chemically different adhesion molecules that regulate lymphocyte traffic, but are believed to be distinct from the inducible adhesion molecules that govern leukocyte adhesion during acute episodes of inflammation. Biochemical and biophysical data indicate that preference of tumor cell adhesion to organ-specific microvascular endothelium may not require qualitative differences of such homing receptors between endothelia, but may be explained on the basis of quantitative receptor differences as well as differences of receptor avidity. Following adhesion, the metastatic cascade proceeds by the establishment of metabolic conduits between the endothelium and adherent tumor cells. This heterotypic coupling represents an early step in the extravasation of cancer cells from the microvasculature, initiating endothelial cell retraction from its basement membrane and recanalization around the arrested tumor cell. These events, together with local growth promoting effects exerted by the metastasized organ, are believed to provide the basis for Paget's seed and soil hypothesis of metastasis.     

Expanding allelic and phenotypic spectrum of ZC4H2-related disorder: A novel hypomorphic variant and high prevalence of tethered cord

ZC4H2 (MIM# 300897) is a nuclear factor involved in various cellular processes including proliferation and differentiation of neural stem cells, ventral spinal patterning and osteogenic and myogenic processes. Pathogenic variants in ZC4H2 have been associated with Wieacker-Wolff syndrome (MIM# 314580), an X-linked neurodevelopmental disorder characterized by arthrogryposis, development delay, hypotonia, feeding difficulties, poor growth, skeletal abnormalities, and dysmorphic features. Zebrafish zc4h2 null mutants recapitulated the human phenotype, showed complete loss of vsx2 expression in brain, and exhibited abnormal swimming and balance problems. Here we report 7 new patients (four males and three females) with ZC4H2-related disorder from six unrelated families. Four of the 6 ZC4H2 variants are novel: three missense variants, designated as c.142T>A (p.Tyr48Asn), c.558G>A (p.Met186Ile) and c.602C>T (p.Pro201Leu), and a nonsense variant, c.618C>A (p.Cys206*). Two variants were previously reported : a nonsense variant c.199C>T (p.Arg67*) and a splice site variant (c.225+5G>A). Five patients were on the severe spectrum of clinical findings, two of whom had early death. The male patient harboring the p.Met186Ile variant and the female patient that carries the p.Pro201Leu variant have a relatively mild phenotype. Of note, 4/7 patients had a tethered cord that required a surgical repair. We also demonstrate and discuss previously under-recognized phenotypic features including sleep apnea, arrhythmia, hypoglycemia, and unexpected early death. To study the effect of the missense variants, we performed microinjection of human ZC4H2 wild-type or variant mRNAs into zc4h2 null mutant zebrafish embryos. The p.Met186Ile mRNA variant was able to partially rescue vsx2 expression while p.Tyr48Asn and p.Pro201Leu mRNA variants were not. However, swimming and balance problems could not be rescued by any of these variants. These results suggest that the p.Met186Ile is a hypomorphic allele. Our work expands the genotypes and phenotypes associated with ZC4H2-related disorder and demonstrates that the zebrafish system is a reliable method to determine the pathogenicity of ZC4H2 variants.     

A narrative review of pelvic floor muscle training in the management of incontinence following prostate treatment

Background and ObjectiveUrinary incontinence following prostate treatment (IPT) is a common complication with corresponding negative impacts on quality of life. Pelvic floor muscle training (PFMT) is a non-invasive treatment strategy to treat combat this clinical issue, and has been recognized by medical associations globally and increasingly supported by large bodies of literature. Accordingly, many studies demonstrate a significant benefit of pelvic floor muscle training to continence status and quality of life in men with incontinence following prostate treatment. However, related research is limited by variety in treatment regimens, outcome measures, and study designs, with unclear impact on treatment success. We aim to provide a brief overview of pathology and incidence of incontinence following prostate surgery and an understanding how PFMT is currently used to treat and prevent this clinical consequence.MethodsA comprehensive literature search was conducted utilizing PubMed, Medline, and Google Scholar. Search criteria included systematic reviews and randomized control trials published in the year 2000 to present. References of resulting studies were further analyzed to identify further articles of relevance. Keywords searched included: “post-prostatectomy incontinence”, “pelvic muscle strengthening”, “Benign Prostatic Hyperplasia”, and “pelvic floor muscle training”. Peer-reviewed publications that demonstrated a novel addition to the existing body of literature on this subject were included.Key Content and FindingsUpon review of the current research landscape, PFMT is largely supported in treatment of IPT. Analysis of current literature on this subject demonstrates heterogeneity in protocols, measures of treatment success, and patient numbers. Nevertheless, benefits to continence and quality of life are noted across an expansive body of literature and as such, PFMT is therefore recommended as an important part of the treatment algorithm following radical prostatectomy.ConclusionsPFMT is an important and effective part of the treatment algorithm in the prevention and treatment of IPT. Additional research is needed to more extensively assess PFMT’s role in treating this clinical consequence, especially following other prostate surgeries.     

Ciliary Muscle Dimension Changes With Accommodation Vary in Myopia and Emmetropia

PurposeThe purpose of this study was to determine whether accommodation-induced changes in ciliary muscle dimensions vary between emmetropes and myopes, and the effect of the image analysis method.MethodsSeventy adults aged 18 to 27 years consisted of 25 people with emmetropia (spherical equivalent refraction [SER] +0.21 ± 0.36 diopters [D]) and 45 people with myopia (−2.84 ± 1.72 D). There were 23 people with low myopia (>−3 D) and 22 people with moderate myopia (−3 to −6 D). Right eye ciliary muscles were imaged (Visante OCT; Carl Zeiss Meditec) at 0 D and 6 D demands. Measures included ciliary muscle length (CML), ciliary muscle curved length (CMLarc), maximum ciliary muscle thickness (CMTmax), CMT1, CMT2, and CMT3 (fixed distances 1–3 mm from the scleral spur), CM25, CM50, and CM75 (proportional distances 25%–75%). Linear mixed model analysis determined effects of refractive groups, race, and demand on dimensions. Significance was set at P < 0.05.ResultsMyopic eyes had greater CML and CMLarc nasally than emmetropic eyes. Myopic eyes had thicker muscles than emmetropic eyes at nasal positions, except CM25 and CMT3, and at CM75 temporally. During accommodation and only nasally, CML reduced in emmetropic and myopic eyes, and CMLarc reduced in myopic eyes only. During accommodation, both nasally and temporally, muscles thickened anteriorly (CMT1 and CM25) and thinned posteriorly (CMT3 and CM75) except for temporal CM75. Moderate myopic eyes had greater temporal CMLarc than low myopic eyes, and the moderate myopes had thicker muscles both nasally and temporally using fixed and proportional distances.ConclusionsPeople with myopia had longer and thicker ciliary muscles than people with emmetropia. During accommodation, the anterior muscle thickened and the curved nasal muscle length shortened, more in myopic than in emmetropic eyes. The fixed distance method is recommended for repeat measures in the same individual. The proportional distance method is recommended for comparisons between refractive groups.     

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.     

Twenty‐five years of deep brain stimulation: Celebrations and apprehensions

The year 2012 marks the 25th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid et al in 1987, initially to treat tremor with DBS of the ventral intermediate nucleus of the thalamus. The subsequent extension of DBS to the subthalamic nucleus (STN), demonstrating its efficacy on virtually all symptoms of advanced Parkinson's disease (PD), sparked an era of intense clinical and research activities, eventually transcending PD and movement disorders to encompass mood and mind. Investigations of the role of DBS in a variety of neurological, psychiatric, cognitive, and behavioral conditions is ongoing. Serendipitous discoveries and advances in functional imaging are providing “new” brain targets for an increasing number of pathologies. Toward the end of this quarter of a century of DBS, there have been some indications that the field may be at risk of gliding down a slippery slope, reminiscent of the excesses of the old‐era DBS. Although there are many reasons this year to celebrate the achievements of 25 years of modern DBS, there are also reasons to fear the opening of a new Pandora's box. © 2012 Movement Disorder Society     

Current status of cardiac CT for the detection of myocardial ischemia

Stress and rest myocardial perfusion imaging using computed tomography (CT) can be accurately and safely performed. CT angiography allows for the anatomic visualization of coronary lesions and the components of atherosclerotic plaque, whereas according to currently available data, CT perfusion imaging improves the diagnostic accuracy for detecting ischemic lesions. However, the radiation exposure and contrast load that are involved cannot be neglected. Owing to the limited number of trials that have been published so far, and the fact that they used a wide variety of image acquisition and stress protocols, a standard acquisition protocol for CT perfusion imaging still needs to be found and evaluated in larger multicenter trials. Therefore, CT perfusion imaging, as opposed to other modalities such as magnetic resonance perfusion, SPECT, or positron emission tomography, cannot yet be regarded as clinical routine, but may be considered in patients with contraindications for other imaging modalities.