Hereditary variant transthyretin amyloidosis (ATTRv) is a rare genetic defect that affects about 5000–10,000 people worldwide, causing amyloidosis secondary to misfolding of mutant transthyretin (TTR) protein fibrils. TTR mutations can cause protein deposits in many extracellular regions of organs, but those deposits in cardiac and axonal cells are the primary cause of this clinical syndrome. Treatment options are limited, but new drugs are being developed. Patisiran, a novel drug, is a liposomal siRNA against TTR that specifically targets this protein, reducing the accumulation of TTR in tissues, with subsequent improvement in both neuropathy and cardiac function. Patisiran is likely to serve as a prototype for the development of further intelligent drug solutions for use in targeted therapy. In this review we summarize the evidence currently available on the treatment of polyneuropathy in people with ATTRv with patisiran. We review the evidence on its efficacy, safety, and indications of use, citing novel and seminal papers on these subjects.

The purpose of this systematic review is to discuss emerging evidence in the field of viscosupplementation for chronic knee pain secondary to Osteoarthritis (OA). This review focuses on types of viscosupplementation that are clinically available currently, evidence to support their use, contraindications, and adverse events. Recent FindingsOA, also known as degenerative joint disease, is the most common form of arthritis in the United States, affecting 54.4 million, or 22.7% of the adult population. The knee is the most common joint affected in OA, with up to 41% involvement, 30% in the hands, and 19% in the hips. The pathophysiology of OA is complex, with contributing factors including mechanical stress to the joint, as well as many person-specific factors such as genetic susceptibility, ethnicity, nutrition, and sex. Treatment modalities include weight control, exercise, non-steroidal and steroidal anti-inflammatory drugs, opioids, intra-articular platelet-rich plasma, placebo, corticosteroid injection, intra-articular viscosupplementation, and surgery. Viscosupplementation consists of injection of hyaluronic acid (HA) into affected joints, intending to restore the physiologic viscoelasticity in the synovial fluid (SF) in the absence of inflammation. HA has also been shown to downregulate pro-inflammatory factors, such as PGE2 and NFkB, and proteases and proteinases known to break down the joint matrix. The contraindications for HA injection are similar to any other injection therapy, and adverse events are usually mild, local, and transient. Viscosupplementation (VS) is effective over placebo and more effective than NSAIDs and corticosteroids in pain reduction and improved functionality; however, guidelines recommend neither for nor against its use, demonstrating variability in the existing evidence base. Current VS options divide primarily into native vs. cross-linked and low-molecular-weight vs. high-molecular-weight. Current treatment options include Hylan g-f-20

Computational identification of putative microRNA (miRNA) targets is an important step towards elucidating miRNA functions. Several miRNA target-prediction algorithms have been developed followed by publicly available databases of these predictions. Here we present a new database offering miRNA target predictions of several binding types, identified by our recently developed modular algorithm RepTar. RepTar is based on identification of repetitive elements in 3′-UTRs and is independent of both evolutionary conservation and conventional binding patterns (i.e. Watson–Crick pairing of ‘seed’ regions). The modularity of RepTar enables the prediction of targets with conventional seed sites as well as rarer targets with non-conventional sites, such as sites with seed wobbles (G-U pairing in the seed region), 3′-compensatory sites and the newly discovered centered sites. Furthermore, RepTar’s independence of conservation enables the prediction of cellular targets of the less evolutionarily conserved viral miRNAs. Thus, the RepTar database contains genome-wide predictions of human and mouse miRNAs as well as predictions of cellular targets of human and mouse viral miRNAs. These predictions are presented in a user-friendly database, which allows browsing through the putative sites as well as conducting simple and advanced queries including data intersections of various types. The RepTar database is available at http://reptar.ekmd.huji.ac.il.

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Context: Chronic neuropathic pain is a common condition, and up to 11.9% of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use. Evidence Acquisition: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the periphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, producing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodulation for chronic pain treatment. Results: Several reported cases and a small number of randomized trials were published in recent years, describing different methods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique. Conclusions: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment.

Purpose of the Review: Chronic low back pain (CLBP) is a major contributor to societal disease burden and years lived with disability. Nonspecific low back pain (LBP) is attributed to physical and psychosocial factors, including lifestyle factors, obesity, and depression. Mechanical low back pain occurs related to repeated trauma to or overuse of the spine, intervertebral disks, and surrounding tissues. This causes disc herniation, vertebral compression fractures, lumbar spondylosis, spondylolisthesis, and lumbosacral muscle strain. Recent Findings: A systematic review of relevant literature was conducted. CENTRAL, MEDLINE, EMBASE, PubMed, and two clinical trials registry databases up to 24 June 2015 were included in this review. Search terms included: low back pain, over the counter, non-steroidal anti-inflammatory (NSAID), CLBP, ibuprofen, naproxen, acetaminophen, disk herniation, lumbar spondylosis, vertebral compression fractures, spondylolisthesis, and lumbosacral muscle strain. Over-the-counter analgesics are the most frequently used first-line medication for LBP, and current guidelines indicate that over-the-counter medications should be the first prescribed treatment for non-specific LBP. Current literature suggests that NSAIDs and acetaminophen as well as antidepressants, muscle relaxants, and opioids are effective treatments for CLBP. Recent randomized controlled trials also evaluate the benefit of buprenorphine, tramadol, and strong opioids such as oxycodone.

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Migraine headache is a common, chronic, debilitating disease with a complex etiology. Current therapy for migraine headache comprises either treatments targeting acute migraine pain or prophylactic therapy aimed at increasing the length of time between migraine episodes. Recent evidence suggests that calcium gene-related peptide (CGRP) is a critical component in the pathogenesis of migraines. Fremanezumab, a monoclonal antibody against CGRP, was recently approved by the Food and