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Introduction: This study used network meta-analysis (NMA) to inform and compare the number needed to treat (NNT), number needed to harm (NNH), and cost per improved outcome (CPIO) associated with more recently approved treatments for anti-acetylcholine receptor antibody-positive (anti-AChR Ab+) generalized myasthenia gravis (gMG)., Methods: Clinical trials of neonatal Fc receptor (FcRn) inhibitors, efgartigimod intravenous (IV) and rozanolixizumab, and complement inhibitors, ravulizumab and zilucoplan, versus placebo (with background conventional treatment) were included in the primary NMA to compare efficacy and safety outcomes. The outputs from the NMAs were used to estimate NNT and NNH of each treatment versus placebo. CPIO (2024 USD) was estimated for a ≥ 3- or ≥ 5-point reduction from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores. Sensitivity analyses were performed adding efgartigimod PH20 subcutaneous (SC) and eculizumab to the NMA., Results: Efgartigimod IV had the lowest NNT versus placebo for achieving a ≥ 3- and ≥ 5-point reduction in QMG, as well as a ≥ 5-point reduction in MG-ADL, whereas rozanolixizumab had the lowest NNT for a ≥ 3-point reduction in MG-ADL. The NNH versus placebo was similar across comparator treatments. Efgartigimod IV had the lowest CPIO among all treatments for all assessed efficacy outcomes. Sensitivity analyses yielded results consistent with primary analysis and indicated that efgartigimod PH20 SC had comparable NNT and CPIO values to efgartigimod IV, whereas eculizumab had comparable NNT and higher CPIO values compared to other complement inhibitors., Conclusions: FcRn inhibitors and complement inhibitors assessed in this study all demonstrated clinical benefit in terms of NNT as well as an acceptable safety profile in terms of NNH. Within the limitations of this meta-analysis, efgartigimod was associated with a favorable benefit-risk profile as well as a better economic value compared to ravulizumab, rozanolixizumab, and zilucoplan as treatments for anti-AChR Ab+ gMG., (© 2024. The Author(s).)

Purpose: This retrospective cohort study describes the characteristics of patients with myasthenia gravis (MG) who developed exacerbations (MG-E) and compares their healthcare utilization (HRU) to patients who did not experience exacerbations (MG-O)., Method: De-identified data from patients who had ≥2 MG-related diagnostic code submissions were extracted from the National Veterans Affairs Health Care Network electronic health records between 1999 and 2022. Descriptive statistics, Kaplan-Meier analysis, and per-patient per-year (PPPY) HRU were used to compare the two patient groups., Results: About 34 % (3603/10,718) of patients with MG developed exacerbations over a median follow-up of 6.8 years. Approximately 52 % of the MG-E cohort had 3 or more exacerbations over the study period, averaging 1.34 (SD 2.50) exacerbations per year. The MG-E cohort had a higher incidence of early-onset MG (7.72 % vs. 4.05 %; p < 0.0001) and higher mean Charlson Comorbidity Index scores before a diagnosis of MG (0.86 vs. 0.59; p < 0.0001). Relative to patients of other racial groups with MG-E, Hispanic and African Americans had higher cumulative incidence of exacerbations over time (p < 0.0001). Additionally, MG-E patients were five times more likely to be intubated compared to MG-O patients (p < 0.0001). Increased PPPY HRU was observed in patients with MG-E compared to patients with MG-O (outpatient visit: 25.05 vs. 14.08; inpatient admission: 0.47 vs. 0.14; ED visit: 0.69 vs. 0.26; ICU stay: 0.08 vs. 0.02, respectively; p < 0.001)., Conclusion: Approximately one-third of patients diagnosed with MG experienced exacerbations, with higher incidences seen among Hispanic and African Americans. MG-E was associated with higher HRU and a higher intubation risk., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This post-hoc analysis evaluates the long-term efficacy of efgartigimod versus placebo in adult patients with generalized myasthenia gravis (gMG) with acetylcholine-receptor autoantibodies (AChR-Ab+), based on data from the ADAPT RCT and its open-label extension ADAPT+., Methods: Changes from baseline in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores were assessed by treatment group over the ADAPT (up to 20 weeks) and ADAPT+ time horizon (extended to 64 weeks for efgartigimod group patients). Response to treatment was defined as 5-point reduction in QMG or 3-point reduction in MG-ADL vs. baseline values., Results: AChR-Ab+ patients treated with efgartigimod spent a substantially greater percentage of time in response in ADAPT based on at least a 5-point change in QMG compared to the placebo group (44 % versus 13 % respectively, p = 0.0034). Analyses based on a 3-point change in MG-ADL in ADAPT showed the percentage of time in response was nearly double for efgartigimod versus placebo (59 % versus 30 % respectively, p = 0.010). These trends were also maintained using different response definitions, as well as in patients with and without prior immune therapy exposure and by time from diagnosis (<7 years versus ≥7 years)., Conclusions: The clinical benefit of efgartigimod was sustained over repeat treatment cycles and maintained over the long term. Response to treatment was consistent regardless of response definition and was repeated in different patient subgroups. Overall, the results of this analysis indicate that efgartigimod is an effective therapeutic option, demonstrating a robust benefit among AChR-Ab+ patients with gMG., Competing Interests: Declaration of competing interest CQ, GP, EB and DG are employees of argenx. SD and AG are employed by Services in Health Economics (SHE). SHE received fees from argenx in relation to this study. James F Howard Jr.: Research funding (paid to his institution) from Ad Scientiam, Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, Centers for Disease Control and Prevention, MGFA, Muscular Dystrophy Association, NIH, PCORI, and UCB Pharma; honoraria/consulting fees from AcademicCME, Alexion, AstraZeneca Rare Disease, argenx, Biologix Pharma, CheckRare CME, F. Hoffmann-LaRoche Ltd., Horizon Therapeutics plc (now Amgen), Medscape CME, Merck EMB Serono, NMD Pharma, Novartis Pharma, PeerView CME, Physicians' Education Resource (PER) CME, PlatformQ CME, Regeneron Pharmaceuticals, Sanofi US, UCB Pharma, and Zai Labs; non-financial support from Alexion AstraZeneca Rare Disease, argenx, Cartesian Therapeutics, Toleranzia AB, UCB Pharma and Zai Labs.RM received funding for Travel, Meeting attendance or Advisory Board participation from Alexion, argenx, Biomarin, Catalyst, SANOFI, Regeneron and UCB., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Glucocorticoids (GCs) are associated with multiple toxicities that have substantial impact on patients. We conducted qualitative interviews with patients to identify the toxicities that are most relevant from their perspective, with the goal of creating a patient-reported companion measure to the Glucocorticoid Toxicity Index (GTI), a clinician-facing instrument., Methods: Thirty-one patients with recent or current GC use participated in concept elicitation interviews. Participants received GC treatment for myasthenia gravis, chronic inflammatory demyelinating polyradiculoneuropathy, vasculitis, or systemic lupus erythematosus. Transcripts were coded following a thematic analysis approach., Results: Participants reported more than 100 toxicities they believed to be associated with their GC medications. Common toxicities included weight gain (87%), increased appetite (84%), insomnia/sleep problems (77%), cognitive impairment/brain fog (71%), easy bruising (68%), anxiety (65%), irritability/short temper (65%), and osteoporosis (39%). These toxicities often centered on self-esteem, neuropsychiatric effects, skin toxicities, and musculoskeletal function. They can be categorized into domains such emphasizing neuropsychiatric, metabolic/endocrine, musculoskeletal, and dermatological effects, highlighting aspects of GC toxicity that patients are uniquely positioned to appreciate and report., Conclusion: Our results confirm that the toxicities associated with GCs are pervasive and diverse, with substantial impact on patients' lives. These data will be used to inform the development of a patient-reported outcome measure assessing GC toxicity. This patient-reported instrument will be designed to complement the clinician-reported GTI, facilitating a more detailed understanding of the nuances of change in GC toxicity., Competing Interests: Declaration of competing interest TAH and LSM are employed by Evidera, a company that received funding from argenx for time spent conducting this research. MNS is the CEO of Steritas, LLC, which holds the licensing rights to the Glucocorticoid Toxicity Index, and reports owning stock in Steritas (the intellectual property of the GTI is owned by the Massachusetts General Hospital). MNS is a co-founder of Steritas. JHS reports consulting fees from ChemoCentryx, Amgen, Roche/Genentech, Sanofi, Bristol-Myers Squib, AbbVie, InflaRx, Kyverna, Novartis, Q32Bio, Steritas, Zenas, Horizon, argenx, Spruce, PPD; owning stock in Steritas; commercial research grants from Roche/Genentech, Sanofi, Bristol-Myers Squib; royalties from UpToDate; non-commercial research grants from NIH/NIAID. JHS is a co-founder of Steritas and serves as the unpaid chair of the Scientific Advisory Board. He has no fiduciary responsibility at the company. GAP, VR, and DG are employees of argenx, who sponsored the study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

There are substantial disease and health-related quality-of-life (HRQoL) burdens for many patients with myasthenia gravis (MG), especially for those whose disease symptoms are not well controlled. HRQoL measures such as the Myasthenia Gravis Quality of Life 15-item revised (MG-QOL15r) and EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) are vital for evaluating the clinical benefit of therapeutic interventions in patients with MG, as they assess the burden of disease and the effectiveness of treatment, as perceived by patients. The phase 3 ADAPT study (NCT03669588) demonstrated that efgartigimod-a novel neonatal Fc receptor inhibitor-was well tolerated and that acetylcholine receptor antibody-positive (AChR-Ab+) participants who received efgartigimod had statistically significant improvements in MG-specific clinical scale scores. The ancillary data reported here, which cover an additional treatment cycle, show that these participants had similar significant improvements in HRQoL measures, the MG-QOL15r and EQ-5D-5L utility and visual analog scales, and that these improvements were maintained in the second treatment cycle. Positive effects on HRQoL were rapid, seen as early as the first week of treatment in both treatment cycles, and maintained for up to 4 weeks in the follow-up-only portion of treatment cycles. The pattern of improvements in HRQoL paralleled changes in immunoglobulin G level, and correlational analyses show that improvements were consistent across HRQoL measures and with clinical efficacy measures in the ADAPT study. The substantial and durable improvements in HRQoL end points in this study demonstrate the broader benefit of treatment with efgartigimod beyond relief of immediate signs and symptoms of gMG., (© 2023. The Author(s).)

Introduction: AIMS Myasthenia Gravis (MG) is an autoimmune neuromuscular disease in which patients suffer from recurrent exacerbation. There are insufficient data measuring the effects of the resources employed before and during acute exacerbation on subsequent disease outcomes. This study aims to identify factors which lead to lengthened hospital stay., Methods: This is a retrospective chart review of acute MG exacerbations requiring hospitalization. Exacerbations were identified using ICD-9/ICD-10 codes and considered the following variables: age and Myasthenia Gravis Foundation of America (MGFA) class at initial MG diagnosis, age and MGFA class at exacerbation, sex, thymectomy, cause of exacerbation, treatment regimen at time of exacerbation, inpatient treatment regimen, length of hospital stay (LOS), intubation, use of noninvasive ventilation, complications, and disposition., Results: Seventy patients with 141 hospitalizations were identified. Crisis management characterized by intubation and plasmapheresis positively correlated with LOS (both p < .001). Almost 1/5 hospitalizations required intubation. Previous thymectomy negatively correlated with LOS (p < .05). In contrast, male sex correlated with longer LOS (p < .05). One-third of hospital stays were followed by discharge to a post-acute care facility, 7% home with home health, and 1 hospitalization resulted in death., Discussion: Plasmapheresis, intubation, and male sex were associated with increased LOS in acute MG exacerbation. Intubation appears to be the strongest predictor of LOS. Those with previous thymectomy had shorter hospital stays. The role of thymectomy in the acute setting merits further analysis., (© 2023. The Author(s).)

Objective: To evaluate real-world utilization patterns of intravenous immunoglobulin (IVIg) among patients with generalized myasthenia gravis (gMG) over 3 years post-IVIg initiation., Methods: Patients with gMG who initiated IVIg treatment were identified from a United States claims database (Symphony Health's Integrated Dataverse [IDV]®, January 1, 2014 - December 31, 2019). The frequency of subsequent IVIg treatment and associated cost during the year post-IVIg initiation were analyzed. Usage patterns of IVIg and concomitant gMG treatments during the year preceding and 3 years post-IVIg initiation were compared., Results: Among 1225 patients with gMG who initiated IVIg treatment, 706 patients (57.6%) received 1 to 5 IVIg treatment courses (intermittent IVIg users), and 519 patients (42.4%) received ≥6 IVIg treatment courses (chronic IVIg users) within the subsequent year. Mean annual medical cost per patient was nearly 2.5-fold higher for chronic vs. intermittent IVIg users ($161,478 vs. $64,888, p < 0.001). The proportion of patients using corticosteroids and nonsteroidal immunosuppressive treatments (NSISTs) was not reduced over the 3-year follow-up period following IVIg initiation, even for patients who continued annual chronic IVIg for 3 consecutive years post-initiation., Conclusions: Nearly half of patients with gMG received chronic and multiple IVIg treatment courses within the first year once initiating IVIg treatment, indicating higher usage than expected. For all IVIg initiators, the proportion of patients using corticosteroids and NSISTs did not decrease over 3 years despite IVIg initiation., (Copyright © 2022. Published by Elsevier B.V.)

Antagonism of the neonatal Fc receptor (FcRn) by efgartigimod has been studied in several autoimmune diseases mediated by immunoglobulin G (IgG) as a therapeutic approach to remove pathogenic IgGs. Whereas reduction of pathogenic titres has demonstrated efficacy in multiple autoimmune diseases, reducing total IgG could potentially increase infection risk in patients receiving FcRn antagonists. The objective of this study was to analyse the effect of FcRn antagonism with efgartigimod on existing protective antibody titres and the ability to mount an immune response after vaccine challenge. Serum levels of total IgG and protective antibodies against tetanus toxoid (TT), varicella zoster virus (VZV), and pneumococcal capsular polysaccharide (PCP) were measured in all patients enrolled in an open-label trial of efgartigimod for the treatment of pemphigus. Vaccine specific-responses were assessed by measuring changes in IgG titres in patients with generalised myasthenia gravis (gMG) who were treated with efgartigimod and who received influenza, pneumococcal, or coronavirus disease 2019 (COVID-19) vaccines during participation in the double-blind trial ADAPT or open-label extension, ADAPT+ ( n  = 17). FcRn antagonism reduced levels of protective anti-TT, anti-VZV, and anti-PCP antibodies and total IgG to a similar extent; anti-TT and anti-VZV titres remained above minimally protective thresholds for the majority of patients, (10/12) 83% and (14/15) 93% respectively. Protective antibodies returned to baseline values upon treatment cessation. Antigen-specific IgG responses to influenza, pneumococcal, and COVID-19 immunisation were detected in patients with gMG who received these vaccines while undergoing therapy with efgartigimod. In conclusion, FcRn antagonism with efgartigimod did not hamper generation of IgG responses but did transiently reduce IgG titres of all specificities.

Background/objectives: While the clinical manifestations of myasthenia gravis (MG) are well understood, its humanistic impact is not. The objective of this systematic literature review (SLR) was to provide a comprehensive understanding of the humanistic burden of MG with regards to psychological symptoms and health-related quality of life (HRQoL) according to patients and caregivers., Methods: A systematic search was conducted on December 27, 2019, in MEDLINE and Embase to identify English-language studies that were published from January 1, 2009-December 27, 2019 and presented relevant information on the humanistic burden among adults with MG and their caregivers. Title/abstract and full-text screening was performed by two investigators, with any discrepancies resolved by a third investigator., Results: Sixty-seven publications were included in the SLR. Compared with the general population, patients with MG experienced worse HRQoL. Studies reporting on psychological symptoms of MG, including depression, anxiety, fatigue, and sleep, were heterogeneous in terms of the scales and instruments used to assess patients, as well as the patient populations themselves. However, in general those with more severe symptoms and hospitalization days had worse depression and anxiety, and fatigue and sleep improved with disease remission and/or improvement. Scores were worse for females compared with males and where evaluated, HRQoL scores generally improved following treatment., Conclusion: While the literature demonstrates that symptoms associated with MG get better with disease improvement and remission, additional options in efficacious therapy that adequately address the disease-related symptoms and also improve HRQoL may contribute to beneficial outcomes in a greater number of patients with MG., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Serum albumin (SA), the most abundant soluble protein in the body, maintains plasma oncotic pressure and regulates the distribution of vascular fluid and has a range of other important functions. The goals of this review are to expand clinical knowledge regarding the functions of SA, elucidate effects of dysregulated SA concentration, and discuss the clinical relevance of hypoalbuminemia resulting from various diseases. We discuss potential repercussions of SA dysregulation on cholesterol levels, liver function, and other processes that rely on its homeostasis, as decreased SA concentration has been shown to be associated with increased risk for cardiovascular disease, hyperlipidemia, and mortality. We describe the anti-inflammatory and antioxidant properties of SA, as well as its ability to bind and transport a plethora of endogenous and exogenous molecules. SA is the primary serum protein involved in binding and transport of drugs and as such has the potential to affect, or be affected by, certain medications. Of current relevance are antibody-based inhibitors of the neonatal Fc receptor (FcRn), several of which are under clinical development to treat immunoglobulin G (IgG)-mediated autoimmune disorders; some have been shown to decrease SA concentration. FcRn acts as a homeostatic regulator of SA by rescuing it, as well as IgG, from intracellular degradation via a common cellular recycling mechanism. Greater clinical understanding of the multifunctional nature of SA and the potential clinical impact of decreased SA are needed; in particular, the potential for certain treatments to reduce SA concentration, which may affect efficacy and toxicity of medications and disease progression., Competing Interests: DG, EL, and JVS are employees of argenx, the manufacturer of efgartigimod (FDA approved in gMG and under investigation in primary immune thrombocytopenia, pemphigus vulgaris and foliaceus, chronic inflammatory demyelinating polyneuropathy, bullous pemphigoid, and idiopathic inflammatory myopathy [myositis]). JTA has received funding from Syntimmune and argenx as part of fee-for-service agreements. ED is a postdoctoral research fellow of the Research Foundation – Flanders (grant number 12X9420N). JEK has participated on the Medical Advisory Committee of Sanofi Genzyme and Plasma Advisory Committee of Haemonetics. DR is the founder of Staten Biotechnology. NS is a member of the scientific advisory board and a speaker for argenx. IS, is supported by the Clinical Research Fund of the University Hospitals Leuven. ESW may receive royalties from patents owned by the UK Medical Research Council, UT Southwestern Medical Center, and Texas A&M University, and has financial interests in argenx, Astero BioPharma LLC, Astero Erado Inc., and Astero Technologies LLC. GV is a paid consultant for argenx. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The development (medical writing and editorial support) of this manuscript received funding from argenx. Authors who are not affiliated with argenx were not paid for their contributions to this work. The funder was involved in conception of design, interpretation of data, writing of this article, and decision to submit it for publication., (Copyright © 2022 Ward, Gelinas, Dreesen, Van Santbergen, Andersen, Silvestri, Kiss, Sleep, Rader, Kastelein, Louagie, Vidarsson and Spriet.)

Introduction: Limited evidence exists for healthcare resource utilization (HCRU) and costs associated with generalized myasthenia gravis (gMG), a rare autoimmune disorder, for adults in the United States., Methods: Adults with ≥1 diagnostic claim for MG between 2014 and 2019 were identified using Symphony Health's Integrated Dataverse®. Using a novel algorithm, HCRU and costs over 12 months following index dates were evaluated for patients with gMG including those with exacerbation events. For patients who experienced crisis events, HCRU and costs were analyzed during the 36 months preceding, during, and 12 months following the events., Results: Mean HCRU and costs were higher for newly diagnosed patients compared with previously diagnosed patients (hospitalizations: 0.46 vs. 0.34; all-cause costs: $26,419.20 vs. $24,941.47; direct costs for gMG treatments: $9,890.37 vs. $9,186.47) and further increased for patients with exacerbation events (hospitalizations: 0.72; all-cause costs: $43,734.15; direct costs for gMG treatments: $21,550.02). For patients who experienced crisis events, HCRU and costs markedly increased during the 12 months immediately before the crisis event (hospitalizations: 1.35; all-cause costs: $49,236.68) compared with the 2 preceding years and increased further during the 12 months following the crisis index date (hospitalizations: 2.78; all-cause costs: $173,956.99). Cost increases were, in large part, attributed to treatments received., Discussion: New diagnosis, exacerbation, and crisis events were drivers of HCRU and cost for patients with gMG. Particularly, high costs of gMG-specific medications associated with intervention for exacerbation and crisis events contributed to increased all-cause costs., Competing Interests: GP, DG, and EB are employees of argenx US Inc., Boston, MA, United States. YL is a paid consultant for and receives grant support from argenx US Inc., Boston, MA, United States. CA, AG, AW, and SB are employees of ZS Associates New York, NY, United States; Princeton, NJ, United States; Bangalore, India and serve as paid consultants for argenx US Inc., Boston, MA, United States., (Copyright © 2022 Phillips, Abreu, Goyal, Li, Whangbo, Gelinas, Brauer and Bhattacharya.)

Since the death of Chief Opechankanough >350 years ago, the myasthenia gravis (MG) community has gained extensive knowledge about MG and how to treat it. This review highlights key milestones in the history of treatment and discusses the current "golden age" of clinical trials. Although originally thought by many clinicians to be a disorder of hysteria and fluctuating weakness without observable cause, MG is one the most understood autoimmune neurologic disorders. However, studying it in clinical trials has been challenging due to the fluctuating nature of the medical condition which impacts MG clinical outcomes. Clinical trials must also account for the possibility of a placebo effect. Because MG is a rare incurable autoimmune disorder, it limits the number of potential patients available to participate in clinical trials. In the last 15 years, however, significant progress has been made with MG randomized clinical trials, resulting in a new drug (eculizumab) for physicians' treatment repertoire and an old technique (thymectomy) confirmed effective for MG. Some of the therapies (eg, thymectomy, corticosteroids, plasma exchange, and intravenous immunoglobulin [IVIg]) have survived the test of time. Others (eg, eculizumab and neonatal Fc receptor inhibitor) are novel and hold promise., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

To evaluate how neurologists make decisions regarding chronic inflammatory demyelinating polyneuropathy (CIDP), we conducted a cross-sectional quantitative survey of 100 community neurologists in the United States. Only 13% cited using the European Federation of Neurological Societies/Peripheral Nerve Society guideline. In addition, variability in treatment approaches existed regarding the dose of IVIg used, the length of IVIg therapy before determining response, the outcome measures used to determine IVIg response, and the protocol for weaning off therapy. Forty-three percent reported giving doses that were lower than the recommended IVIg loading dose for CIDP. Many reported giving nonspecific patient education about the rationale of IVIg use and treatment duration. The finding that approximately half of community neurologists endorsed electrodiagnostic criteria that do not support CIDP diagnosis indicated difficulties relying heavily upon neurophysiologic studies in diagnostic guidelines. More education on CIDP diagnosis and treatment and a clear, actionable, clinically focused guideline would enhance best practices, particularly in the midst of high information flow and multiple guidelines., (Published by Elsevier B.V.)

Multiple quantitative trait loci for blood pressure (BP) are localized in humans and rodent models. Model studies have not only produced human quantitative trait loci homologues but also provided unforeseen mechanistic insights into the function modality of quantitative trait loci actions. Presently, congenic knockins, gene-specific knockout, and in vitro and in vivo function studies were used in a rat model of polygenic hypertension, DSS (Dahl salt sensitive) rats. One gene previously unknown in regulating BP was detected with 1 structural mutation(s) for each of 2 quantitative trait loci classified into 2 separate epistatic modules 1 and 3. C17QTL1 in epistatic module 2 was identified to be the gene Chrm3 encoding the M3R (muscarinic cholinergic 3 receptor), since a single function-enhancing M3R T556M conversion correlated with elevated BP. To definitively prove that the enhanced M3R function is responsible for BP changes by the DSS alleles of C17QTL1, we generated a Chrm3 gene-specific rat knockout. We observed a reduction in BP without tachycardia in both sexes, regardless of the amount of dietary salt, and an improvement in diastolic and kidney dysfunctions. All occurred in spite of a significant reduction in M3R-dependent vasodilation. The previously seen sexual dimorphism for C17QTL1 on BP disappeared in the absence of M3R. A Chrm3-coding variation increased M3R signaling, correlating with higher BP. Removing the M3R signaling led to a decrease in BP and improvements in cardiac and renal malfunctions. A novel pathogenic pathway accounted for a portion of polygenic hypertension and has implications in applying new diagnostic and therapeutic uses against hypertension and diastolic dysfunction.

Introduction: We explored adherence to the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines for the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) by reviewing data from a specialty pharmacy database., Materials and Methods: Clinical and electrophysiologic data were reviewed for 65 consecutive patients treated with intravenous immunoglobulin (IVIG) for CIDP. Three neuromuscular neurologists independently classified cases according to EFNS/PNS criteria as (1) fulfilling CIDP criteria; (2) non-CIDP (neither clinical nor electrophysiologic criteria met); or (3) unknown (insufficient information)., Results: Patients were treated by 31 different community neurologists in 14 states. Only seven patients (11%) met clinical and electrodiagnostic CIDP criteria. The remainder (89%) did not have CIDP (49%) or were unknown (40%). IVIG mean induction dose was 1.25 g/kg, mean maintenance dose 0.79 g/kg, and mean interval between infusions was 23 days., Conclusions: Adherence to EFNS/PNS CIDP diagnostic and treatment guidelines in the general neurologic community was poor. Improved education and awareness of widely available CIDP guidelines are recommended.

Purpose: We reviewed the literature on chronic inflammatory demyelinating polyneuropathy (CIDP) in diabetes mellitus (DM) and explored real-world data on the prevalence and treatment of CIDP within DM., Methods: A literature search of Scopus was performed for the terms chronic inflammatory demyelinating polyradiculoneuropathy, chronic inflammatory demyelinating polyneuropathy, CIDP, and prevalence, incidence, epidemiology, or diabetes; peripheral neuropathy and prevalence or diabetes. We also searched through the reference lists of the resulting publications for additional findings that may have been missed. Additional publications on guidelines for the diagnosis of CIDP and diabetic neuropathy were also included. A descriptive analysis of the 2009-2013 PharMetrics Plus™ Database was performed to estimate the prevalence and treatment of CIDP within the DM population., Results: There is an increasing body of literature suggesting that the prevalence of CIDP tends to be higher in diabetic patients, especially in those of older age. Our real-world data seem to support published findings from the literature. For the total cohort (N=101,321,694), the percent prevalence of CIDP (n=8,173) was 0.008%; DM (n=4,026,740) was 4%. The percent prevalence of CIDP without DM (n=5,986) was 0.006%; CIDP with DM (n=2,187) was 9-fold higher at 0.054%. For patients >50years old, there was a significantly higher percentage of CIDP with DM than CIDP without DM. Approximately 50% of CIDP patients were treated with IVIg, 23%-24% with steroids, 1%-2% with PE, and 20%-23% received no treatment., Conclusions: In addition to the growing evidence of higher prevalence of CIDP in DM, our findings reinforce the need for heightened awareness of the association of CIDP and DM., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)