Discontinuing monoclonal antibodies targeting CGRP pathway after one-year treatment: an observational longitudinal cohort study

BackgroundMonoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.MethodsThis observational longitudinal cohort study was conducted at 10 Italian headache centres. Consecutive adult patients were followed-up for three months (F-UP1–3) after discontinuation of a one-year erenumab/galcanezumab treatment. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly acute medication intake (MAMI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rate, relapse rate to CM, and recurrence of Medication Overuse (MO).ResultsWe enrolled 154 patients (72.1% female, 48.2 ± 11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MAMI, NRS, and HIT-6 progressively increased but were still lower at F-UP3 than baseline (Friedman’s analysis of rank, p < .001). In the F-UP1–3 visits, ≥50% response rate frequency did not differ significantly between CM and HFEM patients. However, the median reduction in response rate at F-UP3 was higher in HFEM (− 47.7% [25th, − 79.5; 75th,-17.0]) than in CM patients (− 25.5% [25th, − 47.1; 75th, − 3.3]; Mann-Whitney U test; p = .032). Of the 84 baseline CM patients who had reverted to episodic migraine, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7%) at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline patients suffering of medication overuse headache ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MAMI, NRS, and HIT-6 and higher response rate in the last month of therapy characterized patients with ≥50% response rate at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p < .01).ConclusionMigraine frequency and disability gradually increased after mAbs anti-CGRP interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.     

Microbial fuel cells for in-field water quality monitoring

The need for water security pushes for the development of sensing technologies that allow online and real-time assessments and are capable of autonomous and stable long-term operation in the field. In this context, Microbial Fuel Cell (MFC) based biosensors have shown great potential due to cost-effectiveness, simplicity of operation, robustness and the possibility of self-powered applications. This review focuses on the progress of the technology in real scenarios and in-field applications and discusses the technological bottlenecks that must be overcome for its success. An overview of the most relevant findings and challenges of MFC sensors for practical implementation is provided. First, performance indicators for in-field applications, which may diverge from lab-based only studies, are defined. Progress on MFC designs for off-grid monitoring of water quality is then presented with a focus on solutions that enhance robustness and long-term stability. Finally, calibration methods and detection algorithms for applications in real scenarios are discussed.

Overview of challenges and opportunities in microbial fuel cells for in-field operation.     

Surgery of spinal nerve schwannoma. Risk of neurological deficit after resection of involved root

When surgically removing a spinal nerve schwannoma, preservation of the involved root is attempted and may be feasible. However, in large tumors, sacrifice of the nerve root is often required to achieve total removal of the tumor, and the resection does not always result in postoperative neurological deficit. The present study was designed to determine the incidence and extent of neurological deficit as correlated with resection of the root, performed between 1976 and 1987 in 86 cases at the time of total removal of spinal schwannoma. Thirty-one patients underwent sacrifice of a root critical for the function of the upper (C5-T1, 14 cases) or the lower extremities (L3-S1, 17 cases). This report is limited to these 31 cases. Only seven patients (23%) developed detachable motor or sensory deficits postoperatively. All deficits were no more than partial loss of strength or sensation. Fifteen of the 31 patients had large tumors with extradural components, which necessitated sacrifice of the entire motor and sensory radix; however, 11 (76%) of these 15 did not develop any deficits referrable to the involved myotome or dermatome. Six cases showed histological characteristics of "neurofibroma," with axons intermingled in the tumor, and none developed a postoperative deficit. Preoperative electromyography was performed in 23 cases. Of 13 patients with findings of denervation, five developed deficits after surgery; the other 10 patients showed no evidence of denervation, and none had deficits after surgery. These results indicate that the spinal roots giving origin to schwannoma are frequently nonfunctional at the time of surgery, and risks of causing disabling neurological deficit after sacrificing these roots are small.     

Long-term pain relief produced by intrathecal morphine infusion in 53 patients.

The present report details the characteristics of the analgesic effects of morphine administered chronically by infusion pumps implanted in 53 patients suffering from terminal metastatic disease. The median postimplant survival time in these patients was 4 months. Patients (mean age 58 years) were characterized according to the duration of pain before pump implantation (mean 16 months), prior consumption of systemic opioids (mean one to six daily analgesic equivalents of morphine), and their response to a trial intrathecal dose of morphine (1 to 2 mg). The median infusion dose at 2 weeks was 3.8 mg/day. The analgesic index, calculated as (quality of pain relief x duration of pain relief in hours)/morphine dose in mg, that was observed after the trial dose of morphine was determined for each patient. A close correlation was observed between the acute (2-week) infusion dose necessary to produce pain relief and the analgesic index such that the infusion dose = -8.0 x log (analgesic index) + 17.1. By 16 weeks, the mean spinal morphine dose for the group had increased by a factor of about 2.5; however, significant variation in the dose incrementation was documented. The maximum increase was observed in patients with a low analgesic index, and this rapid incrementation was usually correlated with an unsatisfactory overall outcome. Evidence that long-term infusion continues to yield analgesia was evidenced in six cases where there was an unanticipated loss of drug infusion and a corresponding increase in parenteral narcotic consumption. These data indicate the long-term efficacy and safety of spinal opioid infusion in patients with terminal cancer, and emphasize the advantage of assessing the sensitivity of the patient to spinal opioids by a standardized trial injection prior to pump placement as a prognostic indication of outcome.     

The Epworth Sleepiness Scale: Conventional Self vs Physician Administration

BackgroundThe Epworth Sleepiness Scale (ESS) is a simple, self-administered questionnaire that provides a measurement of the subject's level of daytime sleepiness, and is widely used for patients with obstructive sleep apnea (OSA). Some works undermined its accuracy. The aim of this study was to compare self-administered ESS scores to physician-administered scores in a sample of patients with suspicion of OSA.MethodsPatients were randomly divided into two groups: group 1, or the self-administered group (n = 113); and group 2, or the physician-administered group (n = 112). Patients in group 1 were asked to complete the ESS in the traditional way; in group 2, the ESS was administered by a sleep-medicine physician. Subjects in both groups underwent diagnostic in-laboratory portable monitoring (PM) within 1 week's time.ResultsThe percentage of questionnaires properly completed was significantly different between groups: 77% (87 of 113) in the group 1 vs 100% (112 of 112) in the group 2 (P = .00). Scores obtained when a physician administered the questionnaire (ESSp) were higher than those when the ESS was self administered (ESSs) (ESSp:12.09 ± 4.1 vs ESSs:10.37 ± 5.49; P = .01). The ESSp was more highly correlated with apnea-hypopnea index and oxygen desaturation index than the ESSs.ConclusionsOur results lead us to consider the physician-administered ESS to be more accurate than the traditional ESS; thus, our suggestion is to validate this new method of administration.     

Stem Cell Therapies to Treat Muscular Dystrophy

Muscular dystrophies are heritable, heterogeneous neuromuscular disorders and include Duchenne and Becker muscular dystrophies (DMD and BMD, respectively). DMD patients exhibit progressive muscle weakness and atrophy followed by exhaustion of muscular regenerative capacity, fibrosis, and eventually disruption of the muscle tissue architecture. In-frame mutations in the dystrophin gene lead to expression of a partially functional protein, resulting in the milder BMD. No effective therapies are available at present. Cell-based therapies have been attempted in an effort to promote muscle regeneration, with the hope that the host cells would repopulate the muscle and improve muscle function and pathology. Injection of adult myoblasts has led to the development of new muscle fibers, but several limitations have been identified, such as poor cell survival and limited migratory ability. As an alternative to myoblasts, stem cells were considered preferable for therapeutic applications because of their capacity for self-renewal and differentiation potential. In recent years, encouraging results have been obtained with adult stem cells to treat human diseases such as leukemia, Parkinson's disease, stroke, and muscular dystrophies. Embryonic stem cells (ESCs) can be derived from mammalian embryos in the blastocyst stage, and because they can differentiate into a wide range of specialized cells, they hold potential for use in treating almost all human diseases. Several ongoing studies focus on this possibility, evaluating differentiation of specific cell lines from human ESCs (hESCs) as well as the potential tumorigenicity of hESCs. The most important limitation with using hESCs is that it requires destruction of human blastocysts or embryos. Conversely, adult stem cells have been identified in various tissues, where they serve to maintain, generate, and replace terminally differentiated cells within their specific tissue as the need arises for cell turnover or from tissue injury. Moreover, these cells can participate in regeneration of more than just their specific tissue type. Here we describe multiple types of muscle- and fetal-derived myogenic stem cells, their characterization, and their possible use in treating muscular dystrophies such as DMD and BMD. We also emphasize that the most promising possibility for the management and therapy of DMD and BMD is a combination of different approaches, such as gene and stem cell therapy.