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Genetic kidney disease is well established as an important cause of pediatric kidney failure, and genetic testing might increase diagnostic accuracy, but evidence is limited. This study was conducted to determine the diagnostic yield and clinical impact of genetic testing for children with kidney failure.
Patients who were diagnosed with kidney failure before 19 years of age at Children's Hospital of Fudan University from 2009 to 2018 and received next-generation sequencing (NGS) were enrolled. The results for likely pathogenic variants in genes known to cause chronic kidney disease (CKD) were analyzed.
A molecular diagnosis was identified in 39.9% (75/188) of children with kidney failure. Specific subtype of clinical category was discerned in 54 (72.0%) patients, kidney disease was reclassified in 7 (9.3%) patients, the unknown etiology of 5 (6.7%) patients was molecularly diagnosed, and the clinical diagnoses of the other 9 (12.0%) patients were confirmed. In addition, genetic diagnosis was considered to have contributed to clinical management, including negating the need for kidney biopsy (26/75, 34.7%), avoiding immunosuppressive therapy (24/75, 32.0%), changing surveillance (48/75, 64.0%), guiding specific treatment (21/75, 28.0%), and guiding peri-transplant management and options for kidney transplantation (12/75, 16.0%). Furthermore, cascade testing was subsequently offered to 34.7% (26/75) of families.
Genetic testing identified a molecular diagnosis in nearly 40% of children with kidney failure. Our results confirm that in children with kidney failure, genetic testing can not only establish a specific molecular diagnosis, but has a significant impact on clinical management.
Genetic testing identified a molecular diagnosis in nearly 40% of children with kidney failure. Our results confirm that in children with kidney failure, genetic testing can not only establish a specific molecular diagnosis, but has a significant impact on clinical management.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with an unclear etiology causing severe inflammation, joint pain, and destruction that increases the chance of disability over time. Dysregulation of various immune signaling cascades regulates the formation of synovial hyperplasia and pannus formation. Imbalance in cytokine levels, predominantly proinflammatory cytokines like TNF-α, IL-1, IL-6, IL-17, and IL-12p70 profoundly influences the disease's pathogenesis. Even though various strategies are adopted to treat arthritis, their side effects and cost limit their usage. This review discusses the multiple pathways involved in the pathogenesis of rheumatoid arthritis, provides a systematic analysis of various phytochemicals, and discusses their potential molecular targets in RA treatment.
The literature mining was done from scientific databases such as PubMed, Europe PMC, Web of Science, Scopus, etc. The terminologies used for literature mining were Rheumatoid arthritis, phytochemicalseumatoid arthritis, phytochemicals, cell signaling pathways, molecular mechanism, etc. RESULTS NF-κB, MAPKs, and JAK-STAT are the key pathways potentially targeted for RA treatment. However, specific susceptible pathways and potential targets remain unexplored. SRT1720 mouse Besides, the phytochemicals remain an immense source to be exploited for the effective treatment of RA, overcoming the demerits of the conventional strategies. Various in vitro and in vivo findings suggest that polyphenols and flavonoids effectively treat RA conditions overcoming the demerits, such as limitations in usage and toxicity. The phytochemicals should be explored in par with the pathological mechanisms with all the available targets to determine their therapeutic efficacy. Through the established therapeutic efficacy, phytochemicals can help developing therapeutics that are safe and efficacious for RA treatment.Myeloma-associated bone disease (MBD) develops in about 80-90% of patients and severely affects their quality of life, as it accounts for the majority of mortality and morbidity. Imaging in multiple myeloma (MM) and MBD is of utmost importance in order to detect bone and bone marrow lesions as well as extraosseous soft-tissue masses and complications before the initiation of treatment. It is required for determination of the stage of disease and aids in the assessment of treatment response. Whole-body low-dose computed tomography (WBLDCT) is the key modality to establish the initial diagnosis of MM and is now recommended as reference standard procedure for the detection of lytic destruction in MBD. In contrast, whole-body magnetic resonance imaging (WBMRI) has higher sensitivity for the detection of focal and diffuse plasma cell infiltration patterns of the bone marrow and identifies them prior to osteolytic destruction. It is recommended for the evaluation of spinal and vertebral lesions, while functional, diffusion-weighted MRI (DWI-MRI) is a promising tool for the assessment of treatment response. This review addresses the current improvements and limitations of WBCT and WBMRI for diagnosis and staging in MM, underlining the fact that both modalities offer complementary information. It further summarizes the corresponding radiological findings and novel technological aspects of both modalities.
The Woven EndoBridge (WEB) can be used to treat wide-necked aneurysms without antiplatelet medications, suggesting it may have advantages in the setting of aneurysmal subarachnoid hemorrhage (aSAH). The goal was assessment of safety and efficacy of WEB in aSAH given the delayed nature of aneurysmal thrombosis.
An international retrospective analysis of patients with aSAH treated with WEB was conducted at 7 tertiary centers from 2016 to 2020. Outcomes included rates of rebleeding, retreatment, complications, and complete occlusion. Furthermore, a systematic review and meta-analysis was conducted from 2011 to 2020 assessing the same outcomes. All pooled event rates were calculated using a random effect model.
Consecutive patients with aSAH harbored 25 aneurysms that were treated with 29 WEB devices. The mean age was 53years, and 65% were female. Zero experienced rebleeding, 2 were retreated, 2 experienced complications, 16 were completely occluded at 3months, and 21 were completed occluded at 9-12months. Meta-analysis of 309 WEB treatments for aSAH from 7 case series revealed 2.
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