Metallic drug-eluting stents have led to significant improvements in clinical outcomes but are inherently limited by their caging of the vessel wall. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations, allowing a “leave nothing behind” approach. Although theoretically appealing, the initial experience with BRS technology was limited by increased rates of scaffold thrombosis compared with contemporary stents. This review gives a broad outline of the current BRS technologies and outlines the refinements in BRS design, procedural approach, lesion selection, and post-procedural care that resulted from early BRS trials.
Metallic drug-eluting stents have led to significant improvements in clinical outcomes but are inherently limited by their caging of the vessel wall. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations, allowing a “leave nothing behind” approach. Although theoretically appealing, the initial experience with BRS technology was limited by increased rates of scaffold thrombosis compared with contemporary stents. This review gives a broad outline of the current BRS technologies and outlines the refinements in BRS design, procedural approach, lesion selection, and post-procedural care that resulted from early BRS trials.
The term “neuropathic pain” (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.
Experimental pain stimuli can be used to simulate patients’ pain experience. We review recent developments in psychophysical pain testing, focusing on the application of the dynamic tests—conditioned pain modulation (CPM) and temporal summation (TS). Typically, patients with clinical pain of various types express either less efficient CPM or enhanced TS, or both. These tests can be used in prediction of incidence of acquiring pain and of its intensity, as well as in assisting the correct choice of analgesic agents for individual patients. This can help to shorten the commonly occurring long and frustrating process of adjusting analgesic agents to the individual patients. We propose that evaluating pain modulation can serve as a step forward in individualizing pain medicine.
This review describes some of the recent developments in imaging aspects of pain in the periphery. It is now possible to image nerves in the cornea non-invasively, to image receptor level expression and inflammatory processes in injured tissue, to image nerves and alterations in nerve properties, to image astrocyte and glial roles in neuroinflammatory processes, and to image pain conduction functionally in the trigeminal ganglion. These advances will ultimately allow us to describe the pain pathway, from injury site to behavioral consequence, in a quantitative manner. Such a development could lead to diagnostics determining the source of pain (peripheral or central), objective monitoring of treatment progression, and, hopefully, objective biomarkers of pain.
Objective: To compare pathologic results obtained via in-office transnasal fiberoptic laryngoscopy (TFL) to those of subsequent direct laryngoscopy in order to assess the accuracy of TFL as a diagnostic tool.
Patients: One hundred and seventeen patients with suspicious laryngeal lesions.
Methods: All patients underwent in-office biopsies. All patients with malignant diagnosis were referred to treatment. All patients with benign diagnosis or carcinoma in situ were referred to direct laryngoscopy for definitive diagnosis. The pathological results of the specimens from both procedures were compared.
Results: Adequate tissue for diagnostic purposes was obtained in 110 of 117 in-office transnasal fiberoptic laryngoscopy biopsies (94.0%). The biopsy results revealed invasive carcinoma in 42 patients (38.2%), carcinoma in situ (CIS) in 17 patients (15.4%), and benign lesions in 51 patients (46.4%). All patients with benign pathologies and carcinoma in situ were referred to biopsy under direct laryngoscopy (five patients refused and were removed from the statistics). The final pathologies identified from the biopsies on direct laryngoscopy revealed that there was an underestimation of the transnasal fiberoptic laryngoscopy results in 33 patients (a false negative rate of 31.4%, 33/105) and an overestimation in one patient. The sensitivity of transnasal fiberoptic laryngoscopy biopsy compared with direct laryngoscopy biopsy was 70.6% and the specificity was 96.7%.
Conclusions: TFL with biopsy is easy, safe, and cost-effective but raises serious doubts about its clinical value due its low sensitivity rate for diagnosing suspicious lesions of the larynx. As such, it is recommended that all patients with a suspicious lesion diagnosed by TFL biopsy as being benign or CIS should be referred to direct laryngoscopy for verification of the findings.
Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system causes microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management.
The closest living relatives of humans are their chimpanzee/bonobo (Pan) sister species, members of the same subfamily “Homininae”. This classification is supported by over 50 years of research in the fields of chimpanzee cultural diversity, language competency, genomics, anatomy, high cognition, psy-chology, society, self-consciousness and relation to others, tool use/production, as well as Homo level emotions, symbolic competency, memory recollection, complex multifaceted problem-solving capabili-ties, and interspecies communication. Language competence and symbolism can be continuously bridged from chimpanzee to man. Emotions, intercommunity aggression, body language, gestures, fa-cial expressions, and vocalization of intonations seem to parallel between the sister taxa Homo and Pan. The shared suite of traits between Pan and Homo genus demonstrated in this article integrates old and new information on human–chimpanzee evolution, bilateral informational and cross-cultural exchange, promoting the urgent need for Pan cultures in the wild to be protected, as they are part of the cultural heritage of mankind. Also, we suggest that bonobos, Pan paniscus, based on shared traits with Austra-lopithecus, need to be included in Australopithecine‟s subgenus, and may even represent living-fossil Australopithecines. Unfolding bonobo and chimpanzee biology highlights our common genetic and cul-tural evolutionary origins.
Aortic valve replacement (AVR) is a treatment of choice for patients with symptomatic severe aortic stenosis (AS). However, a significant proportion of these patients do not undergo surgical AVR due to high-risk features. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative for patients with severe AS who are not candidates for open-heart surgery. Since the introduction of TAVI to the medical community in 2002, there has been an explosive growth in procedures. The balloon-expandable Edwards SAPIEN valve and the self-expanding CoreValve ReValvingTM system contribute the largest patient experience with more than 10,000 patients treated with TAVI to date. Clinical out-comes have stabilized in experienced hands, with 30-day mortality less than 10%. Careful patient selection, growing operator experience, and an integrated multidisciplinary team approach contribute to notable improvement in outcomes. In the first randomized pivotal PARTNER trial, in patients with severe AS not suitable candidates for surgical AVR, TAVI compared with standard therapy, significantly improved survival and cardiac symptoms, but was associated with higher incidence of major strokes and major vascular events. The results of randomized comparison of TAVI with AVR among high-risk patients with AS for whom surgery is a viable option are eagerly awaited to provide further evidence on the applicability of TAVI in these patients.
Phase 1 first-in-human studies with anti-cancer products differ from other phase 1 studies in that they are evaluated in patients rather than healthy volunteers. The rationale design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients. Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies.
Consequently, the conduct of phase 1 clinical trials in oncology requires changes. Corresponding education with particular focus on phase 1 trials and on the complex drug development process needs to be an integrated part of the medical oncology curriculum for physicians and nursing staff. This is a crucial element for institutions to remain or become clinical research sites for phase 1 studies, and to participate in the drug development process of novel anti-cancer compounds in the future.
