Rejected

Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.

Visual snow syndrome is a recently described condition of unknown prevalence. We investigated the prevalence in a representative population sample from the UK and tested the hypothesis that visual snow syndrome is associated with young age, headache, tinnitus and mood impairment.

Pitolisant (Wakix), an orally available, first-in-class antagonist/inverse agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) for the treatment of narcolepsy with or without cataplexy in adults and in the USA (as of August 2019) for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy. Pitolisant was demonstrated to have minimal risk of abuse in preclinical and clinical studies, and is the only anti-narcoleptic drug not scheduled as a controlled substance in the USA. The totality of evidence from pivotal and supportive phase III trials suggests that pitolisant administered at up to the recommended maximum dose of 36 mg once daily reduces EDS and cataplexy in adults with narcolepsy relative to placebo. Noninferiority of pitolisant to modafinil in the management of EDS was not demonstrated. Pitolisant was generally well tolerated in clinical trials. Consistent with its mechanism of action, the most common treatment-emergent adverse events included headache, insomnia and anxiety. With minimal abuse potential and offering the convenience of oral, once-daily administration, pitolisant extends the range of approved treatment options available to adult patients with narcolepsy with or without cataplexy.

In adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal instrumented fusion (PSIF), we aimed to answer these questions: (1) is there a difference in postoperative urinary retention (UR) rates among patients who had removal of their Foley catheters before vs. after discontinuation of epidural analgesia (EA)? (2) Can the timing of Foley catheter removal be an independent risk factor for postoperative UR requiring recatheterization? (3) Is there an incurred cost related to treating UR?

Intra-abdominal infection is the second most common cause of sepsis, and the mortality rate from abdominal sepsis remains high. High molecular weight (HMW) hyaluronic acid (HA) has been studied in sterile injury models as an anti-inflammatory and anti-permeability agent. This study evaluated the therapeutic effects of intraperitoneal HMW HA administration in mice with peritonitis-induced sepsis. Sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP), followed 4 h later by an intraperitoneal injection of HMW HA (20 mg/kg) solution or phosphate buffered saline (PBS). Survival, physiological data, organ injury, bacterial burden, and inflammatory cytokine levels were assessed in the CLP mice. To assess the effect of HA on macrophage phagocytosis activity, RAW264.7 cells, primed with lipopolysaccharide, were exposed with either PBS or HMW HA (500 μg/ml) prior to exposure to 10 CFU of E.coli bacteria. HMW HA instillation significantly improved blood oxygenation, lung histology, and survival in CLP mice. Inflammatory cytokine levels in the plasma and bacterial burdens in the lung and spleen were significantly decreased by HA administration at 24 h after CLP. At 6 h after CLP, HA significantly decreased bacterial burden in the peritoneal lavage fluid. HMW HA administration significantly increased E.coli bacterial phagocytosis by RAW264.7 cells in part through increased phosphorylation of ezrin/radixin/moesin, a known downstream target of CD44 (a HA receptor); ezrin inhibition abolished the enhanced phagocytosis by RAW264.7 cells induced by HA. Intraperitoneal administration of HMW HA had therapeutic effects against CLP-induced sepsis in terms of suppressing inflammation and increasing antimicrobial activity.

To determine the effects of diaphragm-strengthening training on the stability limits of the trunk and inspiratory function in patients with low back pain.

: Retrospective analysis evaluating and comparing the feasibility, effectiveness and safety of intranasal fentanyl (INF) and subcutaneous fentanyl (SCF) for pain management of patients with acute severe pain in a rural/suburban Emergency Medical Services (EMS) system. : Pre- and post-pain management data of all patients (aged ≥14 years) who were transported to the emergency department (January 2015-August 2017) were extracted from EMS and online medical control center records, and compared for groups receiving INF or SCF. Kaplan-Meier analysis and the log-rank test were used to describe and compare the percentage of patients in both groups who experienced relief according to their clinically significant pain relief score. Subgroup analysis was performed by patient age (<70 years, ≥70 years). : 94.6% (SCF = 94.8%; INF = 94.4%) of patients successfully received fentanyl and 82.7% (SCF = 81.2%; INF = 84.0%) had complete data and were included in the analysis. No difference was observed in time to administration or in the effectiveness of INF and SCF, and neither route of administration resulted in major adverse events that required intervention by paramedics. Upon subgroup analysis, INF patients ≥70 years were more likely to experience relief compared to those <70 years. : This retrospective analysis of prehospital patients in the Chaudière-Appalaches EMS system demonstrates that both IN and SC are feasible, effective and safe routes for administering fentanyl. The observed effects of INF were found to be greater among patients ≥70 years. Further research is required to compare these routes with more conventional methods of pain management.

Perioperative pain management in an obese patient is challenging. The incidence of respiratory depression is higher in obese patients and is exaggerated with opioids. We evaluated the efficacy of opioid-free anesthesia with propofol, dexmedetomidine, lignocaine, and ketamine in obese patients undergoing urological laparoscopic procedures with reference to postoperative analgesic consumption, hemodynamic stability, and respiratory depression.

In the therapeutic arsenal to treat moderate to severe psoriasis, the new agents are secukinumab and ustekinumab, which are fully human monoclonal antibodies, directed against IL-17A and IL-12/23, respectively, which have been shown to be effective and safe in several studies. Their side effects are rare, and the most frequently reported side effects were infection, especially nasopharyngitis, headache, pruritus, high blood pressure, and low back pain. Unlike the side effects, the paradoxical reaction can be defined by the appearance or exacerbation of a pathological condition that usually responds to a certain class of drug. The appearance of this reaction in patients using anti-interleukins is poorly described; however, as they are new drugs, they may be more common than the literature reports. We describe a case of a paradoxical reaction, with the appearance of atopic dermatitis, after using secukinumab to treat psoriasis.

Chemotherapy-induced peripheral neuropathy (CIPN) pain significantly worsens cancer survivors' quality of life. Expectancy may play an important role in acupuncture response. We sought to explore whether expectancy predicts pain outcome in real acupuncture (RA) and sham acupuncture (SA) in cancer survivors.