Effectiveness and tolerability of different therapies in preventive treatment of MOG-IgG-associated disorder: A network meta-analysis

BackgroundImmunotherapy has been shown to reduce relapses in patients with myelin oligodendrocyte glycoprotein antibody-associated disorder (MOG-AD); however, the superiority of specific treatments remains unclear.AimTo identify the efficacy and tolerability of different treatments for MOG-AD.MethodsSystematic search in Pubmed, Embase, Web of Science, and Cochrane Library databases from inception to March 1, 2021, were performed. Published articles including patients with MOG-AD and reporting the efficacy or tolerability of two or more types of treatment in preventing relapses were included. Reported outcomes including incidence of relapse, annualized relapse rate (ARR), and side effects were extracted. Network meta-analysis with a random-effect model within a Bayesian framework was conducted. Between group comparisons were estimated using Odds ratio (OR) or mean difference (MD) with 95% credible intervals (CrI).ResultsTwelve studies that compared the efficacy of 10 different treatments in preventing MOG-AD relapse, including 735 patients, were analyzed. In terms of incidence of relapse, intravenous immunoglobulins (IVIG), oral corticosteroids (OC), mycophenolate mofetil (MMF), azathioprine (AZA), and rituximab (RTX) were all significantly more effective than no treatment (ORs ranged from 0.075 to 0.34). On the contrary, disease-modifying therapy (DMT) (OR=1.3, 95% CrI: 0.31 to 5.0) and tacrolimus (TAC) (OR=5.9, 95% CrI: 0.19 to 310) would increase the incidence of relapse. Compared with DMT, IVIG significantly reduced the ARR (MD=−0.85, 95% CrI: −1.7 to −0.098). AZA, MMF, OC and RTX showed a trend to decrease ARR, but those results did not reach significant differences. The combined results for relapse rate and adverse events, as well as ARR and adverse events showed that IVIG and OC were the most effective and tolerable therapies.ConclusionsWhilst DMT should be avoided, IVIG and OC may be suited as first-line therapies for patients with MOG-AD. RTX, MMF, and AZA present suitable alternatives

Cerebrospinal fluid oligoclonal bands in Chinese patients with multiple sclerosis: the prevalence and its association with clinical features

BackgroundCerebrospinal fluid oligoclonal band (CSF-OCB) is an established biomarker in diagnosing multiple sclerosis (MS), however, there are no nationwide data on CSF-OCB prevalence and its diagnostic performance in Chinese MS patients, especially in the virtue of common standard operation procedure (SOP).MethodsWith a consensus SOP and the same isoelectric focusing system, we conducted a nationwide multi-center study on OCB status in consecutively, and recruited 483 MS patients and 880 non-MS patients, including neuro-inflammatory diseases (NID, n = 595) and non-inflammatory neurological diseases (NIND, n=285). Using a standardized case report form (CRF) to collect the clinical, radiological, immunological, and CSF data, we explored the association of CSF-OCB positivity with patient characters and the diagnostic performance of CSF-OCB in Chinese MS patients. Prospective source data collection, and retrospective data acquisition and statistical data analysis were used.Findings369 (76.4%) MS patients were OCB-positive, while 109 NID patients (18.3%) and 6 NIND patients (2.1%) were OCB-positive, respectively. Time from symptom onset to diagnosis was significantly shorter in OCB-positive than that in OCB-negative MS patients (13.2 vs 23.7 months, P=0.020). The prevalence of CSF-OCB in Chinese MS patients was significantly higher in high-latitude regions (41°-50°N)(P=0.016), and at high altitudes (>1000m)(P=0.025). The diagnostic performance of CSF-OCB differentiating MS from non-MS patients yielded a sensitivity of 76%, a specificity of 87%.InterpretationThe nationwide prevalence of CSF-OCB was 76.4% in Chinese MS patients, and demonstrated a good diagnostic performance in differentiating MS from other CNS diseases. The CSF-OCB prevalence showed a correlation with high latitude and altitude in Chinese MS patients

Turbulent Dust-trapping Rings as Efficient Sites for Planetesimal Formation

International audienceRecent observations of protoplanetary disks (PPDs) at submillimeter wavelengths have revealed the ubiquity of annular substructures that are indicative of pebble-sized dust particles trapped in turbulent ringlike gas pressure bumps. This major paradigm shift also challenges the leading theory of planetesimal formation from such pebbles by means of the streaming instability, which operates in a pressure gradient and can be suppressed by turbulence. Here, we conduct 3D local shearing box nonideal magnetohydrodynamic simulations of dust trapping in enforced gas pressure bumps, including dust backreaction. Under a moderate level of turbulence generated by the magnetorotational instability with ambipolar diffusion, which is suitable for outer disk conditions, we achieve quasi-steady states of dust trapping balanced by turbulent diffusion. We find strong dust clumping in all simulations near the gas pressure maxima, reaching a maximum density well above the threshold for triggering gravitational collapse to form planetesimals. A strong pressure bump concentrates dust particles toward the bump's center. With a weak pressure bump, dust can also concentrate in secondary filaments off the bump's center, due to dust backreaction, but strong clumping still occurs mainly in the primary ring around the bump's center. Our results reveal dust-trapping rings to be robust locations for planetesimal formation in outer PPDs, while they may possess diverse observational properties

Effects of local thermal non-equilibrium on hydraulic stimulation efficiency of enhanced geothermal systems

Abstract Motivated by hydraulic stimulation of enhanced geothermal systems, the present paper investigates the coupled thermo-hydro-mechanical response of a geothermal well imbedded in a thermoporoelastic medium, subjected to a non-isothermal fluid flux and convective cooling on the borehole surface. Our focus centers on the effect of local thermal non-equilibrium (LTNE) on the temporal-spatial evolution of temperatures, pore pressure, and stresses, where the solid and fluid phases have two distinct temperatures and local heat transfer between the two phases is addressed. We employ integral transform and load decomposition techniques to derive analytical solutions in the Laplace domain. This methodology allows us to disentangle and separate the individual contributions to changes in pore pressure and stresses from fluid injection and convective heat transfer. The results reveal that compared to the classical local thermal equilibrium model, the thermally induced pore pressure is slightly lower under LTNE conditions. The LTNE has a significant influence on the temporal evolution of thermally induced stresses, especially in the vicinity of the wellbore

Saltmarsh Carbon Stock Changes under Combined Effects of Vegetation Succession and Reclamation

Blue carbon ecosystems have been widely recognized for their carbon sequestration function to mitigate climate changes. However, both natural processes (e.g., interspecific competition) and human activities could alter the ability of blue carbon storage. To clarify the impacts of vegetation succession and reclamation on carbon stock changes, field investigation and laboratory analysis were conducted in a saltmarsh within Hangzhou Bay. Remote sensing data indicated a zonation pattern: the exotic species Spartina alterniflora encroached into the native species Scirpus mariqueter at a rate of 3.51 km2 a−1, but S. mariqueter expanded to the front bare mudflat at a rate of 2.51 km2 a−1. The carbon stock (1 m in depth) was found to be 85.37 Mg C ha−1 for the exotic species, 56.52 Mg C ha−1 for the native species, and 39.78 Mg C ha−1 for the bare mudflat. The carbon burial rate varied among 3 habitats, from 0.63 Mg C ha−1 a−1 in the bare mudflat to 1.39 to 1.59 Mg C ha−1 a−1 in the vegetation sites. Within the study area, vegetation succession contributed an additional 4,858 Mg of organic carbon between 2017 and 2020 to the carbon pool. The organic carbon content of the reclamation site showed a considerable reduction, from 8.51 g kg−1 to 3.34 g kg−1 after 2 years of reclamation, resulting in an emission of 21.61 Mg C ha−1. Overall, the vegetation succession increased the carbon stock of the region while reclamation caused a net carbon loss in the saltmarshes. These findings can enrich the cognition to promote blue carbon management in coastal zones

Protective role of nitric oxide donors on endothelium in ischemia-reperfusion injury: a meta-analysis of randomized controlled trials

Abstract Background Decreased bioavailability of nitric oxide (NO) under hypoxic conditions can lead to endothelial dysfunction. NO supplementation may protect endothelial function in ischemia-reperfusion (IR) injury. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to verify the protective effect of NO donors on endothelium in IR injury. Methods Medline, Embase, Cochrane Library, and Web of Science databases were searched from inception to April 1, 2023. The specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing NO donors with placebo control groups; and (3) trials reporting the effects of these interventions on vascular endothelial functional outcomes in IR injury. Random-effects models were used to assess pooled effect sizes, which were expressed as standardized mean differences (SMD). Results Seven studies satisfied the inclusion criteria and consisted of a total of 149 participants. NO donors were protective of endothelial function in IR injury (SMD: − 1.60; 95% confidence interval [CI]: − 2.33, − 0.88, P < 0.0001; heterogeneity [I2 = 66%, P = 0.001]). Results of the subgroup analysis showed the following: absence of protective effect of NO donor use following ischemia on endothelial function in IR injury − 1.78 (95% CI: − 2.50, − 1.07) and loss of protective effect on endothelial function after prolonged NO donor use − 0.89 (95% CI: − 2.06, 0.28). Conclusion The short-period use of NO donors before the onset of ischemia can protect endothelial function in IR injury

A comprehensive analysis of immune features and construction of an immune gene diagnostic model for sepsis

Abstract Sepsis is a life-threatening syndrome resulting from immune system dysfunction that is caused by infection. It is of great importance to analyze the immune characteristics of sepsis, identify the key immune system related genes, and construct diagnostic models for sepsis. In this study, the sepsis transcriptome and expression profiling data were merged into an integrated dataset containing 277 sepsis samples and 117 non-sepsis control samples. Single-sample gene set enrichment analysis (ssGSEA) was used to assess the immune cell infiltration. Two sepsis immune subtypes were identified based on the 22 differential immune cells between the sepsis and the healthy control groups. Weighted gene co-expression network analysis (WCGNA) was used to identify the key module genes. Then, 36 differentially expressed immune-related genes were identified, based on which a robust diagnostic model was constructed with 11 diagnostic genes. The expression of 11 diagnostic genes was finally assessed in the training and validation datasets respectively. In this study, we provide comprehensive insight into the immune features of sepsis and establish a robust diagnostic model for sepsis. These findings may provide new strategies for the early diagnosis of sepsis in the future

PD-1 blockade immunotherapy as a successful rescue treatment for disseminated adenovirus infection after allogeneic hematopoietic stem cell transplantation

Abstract Disseminated adenovirus infection is a complication with a relatively high mortality rate among patients undergoing hematopoietic stem cell transplantation. The low efficacy and poor availability of current treatment options are of major concern. Programmed cell death 1 (PD-1) blockade has been used to treat several chronic viral infections. Herein, we report a case of disseminated adenovirus infection in the early posttransplant period. The patient was diagnosed with diffuse large B-cell lymphoma at first and underwent 8 cycles of chemotherapy, including rituximab. She was subsequently diagnosed with acute myeloid leukemia and received haploidentical transplantation. She was diagnosed with Epstein‒Barr virus (EBV)-positive posttransplant lymphoproliferative disorder (PTLD) 2 months after the transplant, and 3 doses of rituximab were administered. The patient was diagnosed with disseminated adenovirus infection with upper respiratory tract, gastrointestinal tract and blood involved at 3 months after transplantation. She was first treated with a reduction in immunosuppression, cidofovir and ribavirin. Then, the patient received salvage treatment with the PD-1 inhibitor sintilimab (200 mg) after achieving no response to conventional therapy. The adenovirus was cleared 3 weeks later, and concomitant EBV was also cleared. Although the patient developed graft-versus-host disease of the liver after the administration of the PD-1 inhibitor, she was cured with steroid-free therapy. Therefore, PD-1 blockade immunotherapy can be considered a promising treatment option for patients with disseminated adenovirus infection after transplantation, with fully weighing the hazards of infection and the side effects of this therapy