Time to response with ravulizumab, a long-acting terminal complement inhibitor, in adults with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.

BACKGROUND AND PURPOSE: The efficacy and safety of ravulizumab, a terminal complement C5 inhibitor, in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG) were demonstrated in the CHAMPION MG study (NCT03920293). This analysis aimed to characterize the latency to onset of a clinically meaningful therapeutic effect for ravulizumab. METHODS: Post hoc analysis of data collected for up to 60 weeks from CHAMPION MG was performed to assess the timing of response to ravulizumab. Response was analyzed based on reductions of ≥2 and ≥3 points (minimal clinically important differences [MCIDs]) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores, respectively, and on more rigorous reductions of ≥3 and ≥5 points, respectively. Time to first response was assessed using the Kaplan-Meier product-limit method. RESULTS: The median (95% confidence interval) time to first response was 2.1 (2.1-2.6) and 4.1 (2.3-10.0) weeks for reductions of ≥2 and ≥3 points in MG-ADL total score, respectively (n = 139), and 4.1 (2.1-10.0) and 18.3 (11.0-33.4) weeks for reductions of ≥3 and ≥5 points in QMG total score, respectively (n = 134). Cumulative response rates at Week 60 (data cut-off) were 88% and 82% for ≥2- and ≥3-point MG-ADL score reductions, respectively, and 86% and 59% for ≥3- and ≥5-point QMG score reductions, respectively. CONCLUSIONS: The median times to MCID with ravulizumab treatment in patients with AChR Ab+ gMG were ~2 weeks and ~4 weeks based on MCID MG-ADL and QMG total score reductions, respectively.

Piezoelectric GaGeX2 (X = N, P, and As) semiconductors with Raman activity and high carrier mobility for multifunctional applications: a first-principles simulation.

In the present work, we propose GaGeX2 (X = N, P, As) monolayers and explore their structural, vibrational, piezoelectric, electronic, and transport characteristics for multifunctional applications based on first-principles simulations. Our analyses of cohesive energy, phonon dispersion spectra, and ab initio molecular dynamics simulations indicate that the three proposed structures have good energetic, dynamic, and thermodynamic stabilities. The GaGeX2 are found as piezoelectric materials with high piezoelectric coefficient d 11 of -1.23 pm V-1 for the GaGeAs2 monolayer. Furthermore, the results from electronic band structures show that the GaGeX2 have semiconductor behaviours with moderate bandgap energies. At the Heyd-Scuseria-Ernzerhof level, the GaGeP2 and GaGeAs2 exhibit optimal bandgaps for photovoltaic applications of 1.75 and 1.15 eV, respectively. Moreover, to examine the transport features of the GaGeX2 monolayers, we calculate their carrier mobility. All three investigated GaGeX2 systems have anisotropic carrier mobility in the two in-plane directions for both electrons and holes. Among them, the GaGeAs2 monolayer shows the highest electron mobilities of 2270.17 and 1788.59 cm2 V-1 s-1 in the x and y directions, respectively. With high electron mobility, large piezoelectric coefficient, and moderate bandgap energy, the GaGeAs2 material holds potential applicability for electronic, optoelectronic, piezoelectric, and photovoltaic applications. Thus, our findings not only predict stable GaGeX2 structures but also provide promising materials to apply for multifunctional devices.

Monolayers Sn2Te2X4 (X = P, As) as promising materials for photocatalytic water splitting and flexible devices: a DFT study.

First principles calculation was performed to study the Sn2Te2X4 (X = P, As) monolayers. Structural investigation confirms the stability of the two monolayers with Young's modulus in the range of 30.34-33.65 N m-1 and a Poisson's ratio of 0.18-0.21. The two monolayers are semiconductors with a direct band gap of 1.52-1.66 eV. The light absorption rate of the two monolayers is rather high 104-105 cm-1. Both monolayers have high charge carrier mobility and suitable VBM and CBM positions for the redox reaction. The η STH efficiency of both materials (15.76-17.12%) is close to the theoretical limit of 18%. Moreover, moderate strains can improve the light absorption rate, while the suitable VBM and CBM positions are preserved. These characteristics suggest that Sn2Te2X4 (X = P, As) monolayers are good candidates for being applied in flexible devices and for the conversion of solar energy to other types of energy.

Unveiling Versatile Electronic Properties and Contact Features of Metal-Semiconductor Graphene/γ-Ge2SSe van der Waals Heterostructures.

Recently, searching for a metal-semiconductor junction (MSJ) that exhibits low-contact resistance has received tremendous consideration, as they are essential components in next-generation field-effect transistors. In this work, we design a MSJ by integrating two-dimensional (2D) graphene as the metallic electrode and 2D Janus γ-Ge2SSe as the semiconducting channel using first-principles simulations. All the graphene/γ-Ge2SSe MSJs are predicted to be energetically, mechanically, and thermodynamically stable, characterized by the weak van der Waals (vdW) interactions. The graphene/γ-SGe2Se MSJ-vdWH form the n-type Schottky contact (SC), while the graphene/γ-SeGe2S MSJ-vdWH form the p-type one, suggesting that the switching between p-type and n-type SC in the graphene/γ-Ge2SSe MSJ-vdWHs can occur spontaneously by simply altering the stacking patterns, without requiring any external conditions. Notably, the contact features, including contact types and barriers of the graphene/γ-Ge2SSe MSJs are significant in versatility and can be altered by applying electric gating and adjusting interlayer spacing. Both the applied electric gating and strain engineering induce switchability between p- and n-type and SC to OC in the graphene/γ-Ge2SSE MSJs. This versatility underscores the potential of the graphene/γ-Ge2SSe MSJ for next-generation applications that require low-contact resistance and high performance.

Efficacy and safety of rozanolixizumab in patients with muscle-specific tyrosine kinase autoantibody-positive generalised myasthenia gravis: a subgroup analysis of the randomised, double-blind, placebo-controlled, adaptive phase III MycarinG study.

Background: Muscle-specific tyrosine kinase (MuSK) autoantibody-positive (Ab+) generalised myasthenia gravis (gMG) is a rare and frequently severe subtype of gMG. Objectives: To assess the efficacy and safety of rozanolixizumab in the subgroup of patients with MuSK Ab+ gMG in the MycarinG study. Design: A randomised, double-blind, placebo-controlled phase III study. Methods: Patients with acetylcholine receptor (AChR) Ab+ or MuSK Ab+ gMG (aged ⩾18 years, Myasthenia Gravis Foundation of America Disease Class II-IVa, Myasthenia Gravis Activities of Daily Living [MG-|ADL] score ⩾3.0 [non-ocular symptoms], Quantitative Myasthenia Gravis score ⩾11.0) were randomly assigned (1:1:1) to receive once-weekly subcutaneous infusions of rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg or placebo for 6 weeks, followed by an 8-week observation period. Randomisation was stratified by AChR and MuSK autoantibody status. The primary study endpoint was change from baseline to Day 43 in MG-ADL score. Treatment-emergent adverse events (TEAEs) were also assessed. Results: Overall, 200 patients were randomised, of whom 21 had MuSK Ab+ gMG and received rozanolixizumab 7 mg/kg (n = 5), 10 mg/kg (n = 8) or placebo (n = 8). In patients with MuSK Ab+ gMG, reductions from baseline to Day 43 in MG-ADL scores were observed: rozanolixizumab 7 mg/kg least squares mean (LSM) change (standard error), -7.28 (1.94); 10 mg/kg, -4.16 (1.78); and placebo, 2.28 (1.95). Rozanolixizumab 7 mg/kg LSM difference from placebo was -9.56 (97.5% confidence interval: -15.25, -3.87); 10 mg/kg, -6.45 (-11.03, -1.86). TEAEs were experienced by four (80.0%), five (62.5%) and three (37.5%) patients with MuSK Ab+ gMG receiving rozanolixizumab 7 mg/kg, 10 mg/kg and placebo, respectively. No patients experienced serious TEAEs. No deaths occurred. Conclusion: This subgroup analysis of adult patients with MuSK Ab+ gMG enrolled in the MycarinG study supports the use of rozanolixizumab as an effective treatment option for patients with gMG who have MuSK autoantibodies. Trial registration: ClinicalTrials.gov: NCT03971422 (https://clinicaltrials.gov/study/NCT03971422); EU Clinical Trials Register: EudraCT 2019-000968-18 (https://www.clinicaltrials|register.eu/ctr-search/trial/2019-000968-18/GB).

Rozanolixizumab improved symptoms in people with anti-muscle-specific tyrosine kinase antibody-positive generalised myasthenia gravis in the MycarinG clinical study Myasthenia gravis is a rare, chronic autoimmune disease affecting the communication between nerves and muscles. People with the disease experience fluctuating muscle weakness and fatigue, leading to problems with mobility, speaking, swallowing and breathing. The disease is called generalised when muscles other than those that move the eyes and eyelids are affected. It is caused by antibodies that attack a person's own cells. Most people with the disease have antibodies against acetylcholine receptors (AChRs). However, some have antibodies against the muscle-specific tyrosine kinase (MuSK) protein and can experience more severe symptoms compared with people who have anti-AChR antibodies. Standard treatments for myasthenia gravis do not always work for people with anti-MuSK antibodies. The MycarinG study looked at whether rozanolixizumab was better than a placebo at treating the symptoms of adults with generalised myasthenia gravis and anti-AChR or anti-MuSK antibodies. Assessments measured disease severity and myasthenia gravis symptoms, such as physical fatigue, and how they affected daily activities. The study also looked at whether people receiving rozanolixizumab had any side effects. Here, we look at the group of people with anti-MuSK antibodies who took part in the MycarinG study. In total, 21 of the 200 people in the study had anti-MuSK antibodies. The symptoms of myasthenia gravis improved more in people with anti-MuSK antibodies who received rozanolixizumab than in those who received placebo. Common side effects with rozanolixizumab included headache, diarrhoea and feeling sick. No serious side effects were seen, and no patients died. The results show that rozanolixizumab is an effective treatment for people with generalised myasthenia gravis who have anti-MuSK antibodies. The results in this group of people are consistent with those seen in all people who took part in the study (with either antibody type).

Air pollution, traffic noise, mental health, and cognitive development: A multi-exposure longitudinal study of London adolescents in the SCAMP cohort.

BACKGROUND: There is increasing evidence that air pollution and noise may have detrimental psychological impacts, but there are few studies evaluating adolescents, ground-level ozone exposure, multi-exposure models, or metrics beyond outdoor residential exposure. This study aimed to address these gaps. METHODS: Annual air pollution and traffic noise exposure at home and school were modelled for adolescents in the Greater London SCAMP cohort (N=7555). Indoor, outdoor and hybrid environments were modelled for air pollution. Cognitive and mental health measures were self-completed at two timepoints (baseline aged 11-12 and follow-up aged 13-15). Associations were modelled using multi-level multivariate linear or ordinal logistic regression. RESULTS: This is the first study to investigate ground-level ozone exposure in relation to adolescent executive functioning, finding that a 1 interquartile range increase in outdoor ozone corresponded to -0.06 (p < 0.001) z-score between baseline and follow-up, 38 % less improvement than average (median development + 0.16). Exposure to nitrogen dioxide (NO2), 24-hour traffic noise, and particulate matter < 10 µg/m3 (PM10) were also significantly associated with slower executive functioning development when adjusting for ozone. In two-pollutant models, particulate matter and ozone were associated with increased externalising problems. Daytime and evening noise were associated with higher anxiety symptoms, and 24-hour noise with worse speech-in-noise perception (auditory processing). Adjusting for air pollutants, 24-hour noise was also associated with higher anxiety symptoms and slower fluid intelligence development. CONCLUSIONS: Ozone's potentially detrimental effects on adolescent cognition have been overlooked in the literature. Our findings also suggest harmful impacts of other air pollutants and noise on mental health. Further research should attempt to replicate these findings and use mechanistic enquiry to enhance causal inference. Policy makers should carefully consider how to manage the public health impacts of ozone, as efforts to reduce other air pollutants such as NO2 can increase ozone levels, as will the progression of climate change.

Assessment of physicochemical properties and radioactivity in groundwater at households living in bac Lieu province, vietnam.

This paper presents findings on groundwater physiochemical composition and radioactivity levels in households in Bac Lieu province, Vietnam. Through discriminant analysis, it was observed that groundwater quality exhibits spatial variations corresponding to saline intrusion zones. The paired-samples T-tests revealed significantly different ratios of Ra-224, Ra-226, and Ra-228 isotopes between Na-Cl and Ca-Na-HCO3 water types. All three water types had a ratio of Ra-226/Ra-228 of approximately one, indicating the presence of groundwater aquifers beneath the crust and fluvial marine sediment. Furthermore, strong associations between sulfate and calcium suggest that CO2 enrichment in groundwater aquifers indicates anoxic aquatic environments. Twenty-five of the thirty-three evaluated samples exceeded the national technical regulations for domestic water quality with parameters such as chloride, sulfate, sodium, gross alpha, or total dissolved solids. Fifteen samples exceeded gross alpha's allowable contamination threshold of 0.1 Bq/L. The combination of Ra-226 and Ra-228 did not surpass the U.S. Environmental Protection Agency's recommended limit of 0.185 Bq/L. However, nineteen samples exhibited annual committed effective doses of radium isotopes for infants that exceeded the WHO recommendation of 0.1 mSv/year.

Subcutaneous efgartigimod PH20 in generalized myasthenia gravis: A phase 3 randomized noninferiority study (ADAPT-SC) and interim analyses of a long-term open-label extension study (ADAPT-SC+).

ADAPT-SC (NCT04735432) was designed to evaluate noninferiority of subcutaneous (SC) efgartigimod PH20 to intravenous (IV) efgartigimod in participants with generalized myasthenia gravis (gMG). ADAPT-SC+ (NCT04818671) is an open-label extension study designed to assess long-term safety, tolerability, and efficacy of efgartigimod PH20 SC. Adult participants in ADAPT-SC were randomly assigned to receive a treatment cycle of 4 once-weekly administrations of efgartigimod PH20 SC 1000 â€‹mg or efgartigimod IV 10 â€‹mg/kg, followed by 7 weeks of follow-up. Primary endpoint was percentage change from baseline in total immunoglobulin G (IgG) level at week 4 (1 week after the fourth administration). Secondary efficacy endpoints assessed number and percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) responders and mean change from baseline in total score for each measure. The primary endpoint was met, demonstrating noninferiority in total IgG reduction between efgartigimod PH20 SC 1000 â€‹mg and efgartigimod IV 10 â€‹mg/kg. Clinically meaningful improvements were seen as early as 1 week following the first administration in both treatment arms, with maximal improvements at week 4. Continued treatment cycles of efgartigimod PH20 SC in ADAPT-SC+ have demonstrated long-term safety and consistent improvements in MG-ADL total score. Findings from ADAPT-SC and ADAPT-SC+ demonstrate similar safety and efficacy as observed in the placebo-controlled ADAPT study. Collectively, these findings support noninferiority between efgartigimod PH20 SC 1000 â€‹mg and efgartigimod IV 10 â€‹mg/kg, as well as long-term safety, tolerability, and efficacy of efgartigimod PH20 SC for treatment of a broad population of patients with gMG.

Large piezoelectric responses and ultra-high carrier mobility in Janus HfGeZ3H (Z = N, P, As) monolayers: a first-principles study.

Breaking structural symmetry in two-dimensional layered Janus materials can result in enhanced new phenomena and create additional degrees of piezoelectric responses. In this study, we theoretically design a series of Janus monolayers HfGeZ3H (Z = N, P, As) and investigate their structural characteristics, crystal stability, piezoelectric responses, electronic features, and carrier mobility using first-principles calculations. Phonon dispersion analysis confirms that HfGeZ3H monolayers are dynamically stable and their mechanical stability is also confirmed through the Born-Huang criteria. It is demonstrated that while HfGeN3H is a semiconductor with a large bandgap of 3.50 eV, HfGeP3H and HfGeAs3H monolayers have narrower bandgaps being 1.07 and 0.92 eV, respectively. When the spin-orbit coupling is included, large spin-splitting energy is found in the electronic bands of HfGeZ3H. Janus HfGeZ3H monolayers can be treated as piezoelectric semiconductors with the coexistence of both in-plane and out-of-plane piezoelectric responses. In particular, HfGeZ3H monolayers exhibit ultra-high electron mobilities up to 6.40 × 103 cm2 V-1 s-1 (HfGeAs3H), indicating that they have potential for various applications in nanoelectronics.

Risk factors of postoperative complications and their effect on survival after laparoscopic gastrectomy for gastric cancer.

Background: The association between postoperative complications and long-term survival after laparoscopic gastrectomy (LG) for gastric cancer (GC) remains uncertain. This study aimed to determine the incidence and risk factors of postoperative complications and evaluate their impact on survival outcomes in patients undergoing LG. Methods: A retrospective study was conducted on 621 patients who underwent LG for gastric adenocarcinoma between March 2015 and December 2021. Postoperative complications were classified according to the Clavien-Dindo classification, with major complications defined as Grade III or higher. Logistic regression models with stepwise backward procedure were used to identify risk factors for complications. To assess the impact of postoperative complications on survival, uni- and multi-variable Cox proportional hazard models were used for overall survival (OS) and disease-free survival (DFS). Results: Overall rate of postoperative complications was 17.6% (109 patients); 33 patients (5.3%) had major complications. Independent risk factors for major complications were Charlson comorbidities index (OR [95% CI], 1.87 [1.09-3.12], p-value = 0.018 for each one score increase), and type of anastomosis (OR [95% CI], 0.28 [0.09-0.91], p-value = 0.029 when comparing Billroth II with Billroth I). Multivariable analysis identified major complications as an independent prognostic factor to reduce OS (HR [95% CI], 2.32 [1.02-5.30], p-value = 0.045) and DFS (HR [95% CI], 2.63 [1.37-5.06], p-value = 0.004). Other prognostic factors for decreased survival outcomes were tumor size, presence of invasive lymph nodes, and T4a stage. Conclusions: Major complications rate of LG for GC was approximately 5.3%. Charlson comorbidities index and type of anastomosis were identified as risk factors for major postoperative complications. Major complications were demonstrated to pose adverse impact on survival outcomes.

Pembrolizumab-induced vasculitis demonstrated by FDG-PET/CT.

A 76-year-old man with a history of malignant pleural mesothelioma treated with pembrolizumab underwent FDG-PET/CT for restaging. The images demonstrated FDG uptake overlying the right hepatic and splenic artery, which were new from the previous FDG-PET/CT 2.5 years prior before the patient started pembrolizumab, suspicious for vasculitis. A follow-up MRI supported the diagnosis with evidence of celiac, splenic, common hepatic, and right hepatic artery involvement. Pembrolizumab was discontinued and the patient received a short course of oral glucocorticoids. Subsequent FDG-PET/CT performed 14 months after initiation of treatment for vasculitis demonstrated resolution of vasculitis. Immune checkpoint inhibitors can cause vasculitis, which can be recognized on FDG-PET/CT and lead to appropriate treatment.

A first-principles prediction of novel Janus ZrGeZ3H (Z = N, P, and As) monolayers: Raman active modes, piezoelectric responses, electronic properties, and carrier mobility.

In this article, an attempt is made to explore new materials for applications in piezoelectric and electronic devices. Based on density functional theory calculation, we construct three Janus ZrGeZ3H (Z = N, P, and As) monolayers and study their stability, piezoelectricity, Raman response, and carrier mobility. The results from phonon dispersion spectra, ab initio molecular dynamics simulation, and elastic coefficients confirm the structural, thermal, and mechanical stability of these proposed structures. The ZrGeZ3H monolayers are indirect band gap semiconductors with favourable band gap energy of 1.15 and 1.00 eV for the ZrGeP3H and ZrGeAs3H, respectively, from Heyd-Scuseria-Ernzerhof functional method. It is found that the Janus ZrGeZ3H monolayers possess both in-plane and out-of-plane piezoelectric coefficients, revealing that they are potential piezoelectric candidates. In addition, the carrier mobilities of electrons and holes along transport directions are anisotropic. Notably, the ZrGeP3H and ZrGeAs3H monolayers have high electron mobility of 3639.20 and 3408.37 cm2 V-1 s-1, respectively. Our findings suggest the potential application of the Janus ZrGeZ3H monolayers in the piezoelectric and electronic fields.

Perception of having children through surrogacy in individuals with MRKH in Vietnam: a qualitative study.

Introduction: Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is rare condition that has a negative impact on quality of life because affected women lack a uterus and vagina, and are therefore unable to engage in sexual intercourse and experience natural pregnancy. This study evaluated perceptions of surrogacy in Vietnamese women with MRKH who have started families. Method: Women with MRKH who had undergone successful vaginal reconstruction, were married, and had started families participated in a semi-structured, in-depth, one-on-one online video interview with an experienced female psychologist. Open-ended questions were used to encourage participants to express their perceptions of surrogacy; prominent themes were discussed, compared, and combined. Results: Twenty women (mean age 31 years) agreed to participate. Key themes identified from interviews were the importance of having genetic offspring, consideration of surrogacy as a preferred solution to infertility, the barriers to surrogacy in Vietnam, lack of reproductive information and counselling, individuals concealing their health condition, the impact of religion on the possibility of surrogacy, the economic cost of surrogacy, and the difficulty in finding a surrogate under the restrictions imposed by Vietnamese law. Discussion: Based on the perceptions of women from MRKH from Vietnam, there is an opportunity to improve how infertility is managed in these people, including information about surrogacy. These data show that individuals with MRKH should be provided with information about the possibility of surrogacy, encouraged to be open and seek support, and be managed by a multidisciplinary team that includes psychological support; the provision of economic support for fertility treatments in women with MRKH should also be considered.

Propyne: Determination of Physical Properties and Unit Cell Parameters under Titan-Relevant Conditions.

With its large size, dense atmosphere, methane-based hydrological-like cycle, and diverse surface features, the Saturnian moon Titan is one of the most unique of the outer Solar System satellites. Study of the photochemically produced molecules in Titan's atmosphere is critical in order to understand the mechanics of the atmosphere and, by extension, the interactions between atmosphere, surface, and subsurface water ocean. One example is propyne vapor, a photochemically produced species in Titan's upper atmosphere expected to condense in Titan's stratosphere at lower altitudes. Propyne may also be a trace species in Titan's stratospheric co-condensed ice clouds detected by the Cassini Composite InfraRed Spectrometer. Bulk structural characterization of propyne ice is currently incomplete and is lacking in published laboratory Raman spectra and X-ray diffraction data. Here, we present a laboratory characterization of propyne ice, including the first published X-ray diffraction and Raman spectroscopy results for propyne ice.

Long-term safety and efficacy of zilucoplan in patients with generalized myasthenia gravis: interim analysis of the RAISE-XT open-label extension study.

Background: Generalized myasthenia gravis (gMG) is a chronic, unpredictable disease associated with high treatment and disease burdens, with a need for more effective and well-tolerated treatments. Objectives: To evaluate the long-term safety, tolerability, and efficacy of zilucoplan in a mild-to-severe, acetylcholine receptor autoantibody-positive (AChR+) gMG population. Design: Ongoing, multicenter, phase III open-label extension (OLE) study. Methods: Eligible patients had completed a qualifying randomized, placebo-controlled phase II or phase III zilucoplan study and received daily, self-administered subcutaneous 0.3 mg/kg zilucoplan. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score. Results: In total, 200 patients enrolled. At the cut-off date (8 September 2022), median (range) exposure to zilucoplan in RAISE-XT was 1.2 (0.11-4.45) years. Mean age at OLE baseline was 53.3 years. A total of 188 (94%) patients experienced a TEAE, with the most common being MG worsening (n = 52, 26%) and COVID-19 (n = 49, 25%). In patients who received zilucoplan 0.3 mg/kg in the parent study, further improvements in MG-ADL score continued through to Week 24 (least squares mean change [95% confidence interval] from double-blind baseline -6.06 [-7.09, -5.03]) and were sustained through to Week 60 (-6.04 [-7.21, -4.87]). In patients who switched from placebo in the parent study, rapid improvements in MG-ADL score were observed at the first week after switching to zilucoplan; further improvements were observed at Week 24, 12 weeks after switching (-6.46 [-8.19, -4.72]), and were sustained through to Week 60 (-6.51 [-8.37, -4.65]). Consistent results were observed in other efficacy endpoints. Conclusion: Zilucoplan demonstrated a favorable long-term safety profile, good tolerability, and sustained efficacy through to Week 60 with consistent benefits in a broad AChR+ gMG population. Additional long-term data will be available in future analyses. Trial registration: ClinicalTrials.gov identifier: NCT04225871 (https://clinicaltrials.gov/ct2/show/NCT04225871).

The effects of free trade agreements on the stock market: Evidence from Vietnam.

This study examines the effects of news events related to the European Union-Vietnam Free Trade Agreement (EVFTA) on the Vietnam stock market from 2010 to 2020. We calculate sectoral abnormal returns prior to, during, and after announcements and find that the Vietnamese stock market is susceptible to these events. We discovered that the announcement had a negative impact on the market, which might diminish the effectiveness of the Agreement. The findings show that more than half of Vietnam's sectors had an immediate reaction to EVFTA announcements, with fourteen reacting negatively and six responding positively. Two of the ten events did not have any immediate impact on these industries but all events resulted in either early or delayed reactions. We also find market scepticism and major changes in the deal led to the emergence of a diamond risk structure. We run multiple robustness tests to account for market integration and other factors that may affect stock returns. In addition, we explore potential sectoral systematic risk changes following these occurrences using different ARCH-type models. These additional tests confirm the robustness of our findings.

Efficacy of ravulizumab in patients with generalized myasthenia gravis by time from diagnosis: A post hoc subgroup analysis of the CHAMPION MG study.

INTRODUCTION/AIMS: The CHAMPION MG study demonstrated that ravulizumab significantly improved Myasthenia Gravis-Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) total scores versus placebo in adults with acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR+ gMG). This post hoc analysis aimed to assess these outcomes by time from MG diagnosis. METHODS: Changes from baseline to week 26 in MG-ADL and QMG total scores were analyzed by time from MG diagnosis to study entry (≤2 vs. >2 years). Within each subgroup, least-squares (LS) mean changes for ravulizumab and placebo were compared using mixed models for repeated measures. RESULTS: In ravulizumab-treated patients, differences in LS mean (standard error of the mean) changes from baseline to week 26 were not statistically significant in the ≤2-years subgroup versus the >2-years subgroup for MG-ADL (-4.3 [0.70] vs. -2.9 [0.37]; p = .0511) or QMG (-4.3 [0.94] vs. -2.5 [0.50]; p = .0822) scores. No clear trends were observed in the placebo group. LS mean changes from baseline were significantly greater for ravulizumab versus placebo in both the ≤2 and >2 years from diagnosis subgroups for MG-ADL and QMG scores (all p < .05). The difference in treatment effect between the ≤2-years and >2-years subgroups was not statistically significant. No clinically meaningful between-subgroup differences in treatment-emergent adverse events were observed in ravulizumab-treated patients. DISCUSSION: Ravulizumab treatment improved clinical outcomes for patients with AChR+ gMG regardless of time from diagnosis. A numerical trend was observed favoring greater treatment effect with earlier versus later treatment after diagnosis. Further studies are required for confirmation.

Stomach-partitioning versus conventional gastrojejunostomy for unresectable gastric cancer with gastric outlet obstruction: A propensity score matched cohort study.

BACKGROUND: Stomach partitioning gastrojejunostomy (SPGJ) was introduced to deal with delayed gastric emptying (DGE). This study aimed to compare the short- and long-term outcomes of SPGJ versus conventional gastrojejunostomy (CGJ). METHOD: This cohort study analyzed 108 patients who underwent gastrojejunostomy for unresectable gastric cancer: 70 patients underwent SPGJ, and 38 patients underwent CGJ between 2018 and 2022. Propensity score-matched (PSM) analysis was used to balance the baseline characteristics. RESULTS: After PSM, there were 26 patients in each group. SPGJ group had significantly lower incidence of DGE (3.8% vs. 34.6%), vomiting (3.8% vs. 42.3%), and prokinetics requirement (11.5% vs. 46.2%). SPGJ group had significantly shorter time to solid diet tolerance (4.1 days vs. 5.7 days) and postoperative hospital stay (7.7 days vs. 9.3 days). There was no significant difference in relapse reinterventions, gastric outlet obstruction (GOO) recurrence, conversion surgery, and survival outcomes. CONCLUSIONS: SGPJ was associated with lower rate of DGE, prokinetics requirement, and shorter time of solid diet tolerance compared to CGJ in the treatment of unresectable gastric cancer patients with GOO.

Effect of efgartigimod on muscle group subdomains in participants with generalized myasthenia gravis: post hoc analyses of the phase 3 pivotal ADAPT study.

BACKGROUND AND PURPOSE: Generalized myasthenia gravis (gMG) is a rare, chronic, neuromuscular autoimmune disease mediated by pathogenic immunoglobulin G (IgG) autoantibodies. Patients with gMG experience debilitating muscle weakness, resulting in impaired mobility, speech, swallowing, vision and respiratory function. Efgartigimod is a human IgG1 antibody Fc fragment engineered for increased binding affinity to neonatal Fc receptor. The neonatal Fc receptor blockade by efgartigimod competitively inhibits endogenous IgG binding, leading to decreased IgG recycling and increased degradation resulting in lower IgG concentration. METHODS: The safety and efficacy of efgartigimod were evaluated in the ADAPT study. Key efficacy outcome measures included Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. Efgartigimod demonstrated significant improvement in both the MG-ADL and QMG scores. This post hoc analysis aimed to determine whether all subdomains of MG-ADL and QMG improved with efgartigimod treatment. Individual items of MG-ADL and QMG were grouped into four subdomains: bulbar, ocular, limb/gross motor and respiratory. Change from baseline over 10 weeks in each subdomain was calculated for each group. RESULTS: Greater improvements from baseline were seen across MG-ADL subdomains in participants treated with efgartigimod compared with placebo. These improvements were typically observed 1 to 2 weeks after the first infusion and correlated with reductions in IgG. Similar results were observed across most QMG subdomains. CONCLUSIONS: These post hoc analyses of MG-ADL and QMG subdomain data from ADAPT suggest that efgartigimod is beneficial in improving muscle function and strength across all muscle groups, leading to the observed efficacy in participants with gMG.