Rejected

A 41 year-old man, recently returned from Thailand, presented with bilateral shoulder pain and weakness, fever greater than 38 degrees and coryzal symptoms. He had no significant past medical history. He had abnormal liver function tests and an abnormal electromyogram of his right upper limb. He was diagnosed with acute Epstein Barr virus infection, however cerebrospinal fluid was negative for the virus. At follow up after three months, the patient had persistent weakness of his right upper limb. The literature suggests neurological features present in up to 7.5% of patients with Epstein Barr virus, although argues this is underestimated with the virus often being overlooked as a cause of neurological symptoms.

The aim of this study was to examine the relationship between migraines and obesity, insulin resistance (IR), and metabolic syndrome in female migraineurs.

Neurogenic heterotopic ossifications (NHO) are very incapacitating complications of traumatic brain and spinal cord injuries (SCI) which manifest as abnormal formation of bone tissue in periarticular muscles. NHO are debilitating as they cause pain, partial or total joint ankylosis and vascular and nerve compression. NHO pathogenesis is unknown and the only effective treatment remains surgical resection, however once resected, NHO can re-occur. To further understand NHO pathogenesis, we developed the first animal model of NHO following SCI in genetically unmodified mice, which mimics most clinical features of NHO in patients. We have previously shown that the combination of (1) a central nervous system lesion (SCI) and (2) muscular damage (via an intramuscular injection of cardiotoxin) is required for NHO development. Furthermore, macrophages within the injured muscle play a critical role in driving NHO pathogenesis. More recently we demonstrated that macrophage-derived oncostatin M (OSM) is a key mediator of both human and mouse NHO. We now report that inflammatory monocytes infiltrate the injured muscles of SCI mice developing NHO at significantly higher levels compared to mice without SCI. Muscle infiltrating monocytes and neutrophils expressed OSM whereas mouse muscle satellite and interstitial cell expressed the OSM receptor (OSMR). recombinant mouse OSM induced tyrosine phosphorylation of the transcription factor STAT3, a downstream target of OSMR:gp130 signaling in muscle progenitor cells. As STAT3 is tyrosine phosphorylated by JAK1/2 tyrosine kinases downstream of OSMR:gp130, we demonstrated that the JAK1/2 tyrosine kinase inhibitor ruxolitinib blocked OSM driven STAT3 tyrosine phosphorylation in mouse muscle progenitor cells. We further demonstrated that STAT3 tyrosine phosphorylation was not only significantly higher but persisted for a longer duration in injured muscles of SCI mice developing NHO compared to mice with muscle injury without SCI. Finally, administration of ruxolitinib for 7 days post-surgery significantly reduced STAT3 phosphorylation in injured muscles as well as NHO volume at all analyzed time-points up to 3 weeks post-surgery. Our results identify the JAK/STAT3 signaling pathway as a potential therapeutic target to reduce NHO development following SCI.

To evaluate the prevalence and clinical features of Fabry disease in patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis.

The current treatment of migraine attacks is triptans and NSAIDs, but the calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide target for migraine therapy. Despite an off target class effect on liver enzymes, two CGRP receptor antagonists, ubrogepant and rimegepant, remain in development, together with a 5-HT receptor agonist (lasmiditan), for which cardiovascular contraindications that limit the utility of triptans do not exist. Importantly, to avoid an excessive use of acute medication with the risk of medication overuse, prophylactic therapeutics are the best choice. To date, monoclonal antibodies which block CGRP actions are on the market all over the world but not yet in France. The research is very active in different directions and targets notably hypothalamic neuropeptides because the hypothalamus hosts many key neuropeptide systems that seem to play a role in migraine physiopathology. These neuropeptides include orexins, oxytocin, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide (PACAP). In addition, other promising drugs for the treatment of migraine are nitric oxide synthase inhibitors and acid-sensing ion channel (ASIC) blockers.

Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients' quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients' QoL.

Trichomonas vaginalis is the most common curable sexually transmitted infection (STI) worldwide. Although predominately asymptomatic, the disease spectrum of trichomoniasis in women is characterized primarily by signs and symptoms of vaginitis, including purulent discharge and localized vulvar pruritus and erythema. Several FDA-cleared nucleic acid amplification tests (NAATs) are available for the diagnosis of T. vaginalis infections, but laboratory developed tests (LDTs) are widely utilized and cost-effective solutions in both the research and clinical diagnostic settings. LDT diagnosis of T. vaginalis is particularly appealing since it can be performed using remnant specimens collected for other STI testing. Using a LDT implemented as part of this study, T. vaginalis was detected in 7% of participating Louisiana women (14/199). The mean T. vaginalis organism burden was 1.0×106 ± 4.5×105 organisms per mL of ThinPrep PreservCyt. Using DNA eluates obtained after HPV testing on the cobas 4800 system, the T. vaginalis LDT was characterized by excellent intra- and interassay reproducibility (coefficient of variation values all <3.5%). Compared with two commercially available NAATs from TIB MOLBIOL, the sensitivity and specificity of the LDT was 92.9 and 99.5%, respectively. Collectively, this study details the diagnostic and quantitative utility of a LDT for T. vaginalis. When applied in the clinical research setting, we confirmed the high prevalence of T. vaginalis, but also observed extraordinarily high organism burdens in the cervix. These findings highlight the unique host-pathogen relationship of T. vaginalis with lower reproductive tract tissues, and substantiate the need for continued investigation of this highly prevalent STI.

Chronic pain in patients with Alzheimer's disease or dementia is a complex issue in the medical field; these patients suffer from the common causes of chronic pain, especially in geriatric medicine. To ensure the correct type and level of given treatment, medical care should be taken to avoid the contribution of chronic pain and cognitive impairment in the elderly population. Acetylcholinesterase inhibitors (AChE-Is) have been proven as an efficient therapeutic resource for significant improvement in dementia of Alzheimer's disease and chronic pain due to the fact that cholinergic deficit is considered as an early finding in cognitive impairment and persisting pain. Some AChE-Is are investigated here in terms of treatment of dementia and chronic pain management. Neostigmine has been used as an adjunct analgesic in the postoperative period and in combination with other analgesic medications in an intrathecal approach. Rivastigmine has, over the past ten years, become the approved agent for the management of dementia of mild to moderate Alzheimer's disease and has gained approval for treating different types of non-Alzheimer's dementia. In this review, we will focus on the two types of AChE-Is (rivastigmine and neostigmine) in the development of their clinical use and their respective mechanisms of actions on improving cognitive function and managing chronic pain.

To evaluate effectiveness, tolerability and safety of an oromucosal spray containing Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as add-on treatment in patients with severe chronic pain (SCP). Exploratory analysis of anonymized 12-week routine/open-label data provided by the German Pain e-Registry (GPR) on adult SCP patients treated with THC:CBD oromucosal spray in 2017. Among those 30.228 cases documented in the GPR in 2017, 800 (2.6%; 57% female, mean ± SD age: 46.3±9.7 years) received a treatment with THC:CBD. All patients fulfilled the legislative preconditions for a treatment with cannabis as medicine as defined by the German Act Amending Narcotics and Other Regulations. THC:CBD-treatment was followed by an aggregated nine-factor symptom relief (ASR-9) improvement at end of week 12 vs baseline of 39.0±26.5% (95%-CI: 36.9-41.1, median: 42, range -41 to 85). A full ASR-9 response (ie, a 50%-improvement in all 9 factors) was found for 123 patients (15.4%), while 488 patients (56.0%) presented with an ≥50% improvement in at least 5 of 9 ASR factors. With a 54.9±17.2% (median: 56%, range: -6 to 85) improvement was significantly superior in the neuropathic pain subgroup (n=497, 62.1%) vs those with mixed (n=249, 31.1%; ASR-9: 18.2±12.0, median: 19, range: -12 to 42%) or nociceptive pain (n=54, 6.8%; ASR-9: -11.9±10.5, median: -11, range: -41% to 12%; <0.001 for each). 159 patients (19.9%) reported at least one of 206 TEAEs, most of them of mild intensity (n=81.6%). Most frequently reported TEAEs were increased appetite (n=50, 6.3%) and dysgeusia (n=23, 2.9%). TEAE-related discontinuations were reported for 32 patients (4.0%). 113 (14.1%) patients discontinued due to inadequate pain relief, most of them with nociceptive pain (n=40, 74.1%), least with neuropathic pain (n=1, 0.2%; <0.001). THC:CBD oromucosal spray proved to be an effective and well-tolerated add-on treatment for patients with elsewhere refractory chronic pain – especially of neuropathic origin.

Intracranial dural arteriovenous fistulas (DAVFs) are abnormal arteriovenous connections within the dura, in which meningeal arteries shunt blood directly into the dural sinus or leptomeningeal veins. Among all the treatment options for the treatment of DAVFs, stereotactic radiosurgery (SRS) is a safe and effective modality. SRS provides a minimally invasive therapy for patients who harbor less aggressive DAVFs without cortical vein drainage (CVD), but who suffer from intolerable headache, bruit, or ocular symptoms. For more aggressive DAVFs with CVD associated with immediate risks of hemorrhage, initial treatment with endovascular embolization or surgery for the prompt elimination of the aggressive components of DAVFs is necessary. In such cases, radiosurgery may serve as a secondary treatment for further management of residual nidus after initial intervention. The latent period for the effects of radiation to occur and the longer time for cure compared to surgery and endovascular therapy remains a major drawback for radiosurgery. However, the gradual obliteration of a DAVF after radiosurgery can avoid the immediate risk of aggravated venous hypertension or infarction, which sometimes complicates endovascular embolization and surgery.