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Biomedicines May 2024TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and...
TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those of typical iMCD, as they include a more aggressive clinical course and high mortality. However, an optimal treatment strategy for TAFRO syndrome has not yet been established, owing to a poor understanding of its pathogenesis. The limited cases we encountered suggest that tacrolimus treatment in combination with glucocorticoids may potentially be effective and well tolerated as an initial treatment, and hold promise as a glucocorticoid-sparing agent. Herein, we report an additional case and review the sparse literature available regarding TAFRO syndrome treated via tacrolimus.
PubMed: 38791031
DOI: 10.3390/biomedicines12051070 -
European Review For Medical and... Jul 2023Acute spinal cord injury (SCI) is a devastating disease that causes immense physical and mental harm to the patient and the family, and society and requires a... (Review)
Review
Acute spinal cord injury (SCI) is a devastating disease that causes immense physical and mental harm to the patient and the family, and society and requires a multidisciplinary approach to treatment. The study of acute SCI has a long history but is still emerging. As the mechanism and pathophysiology of acute SCI are continuously being studied and explored, the treatment of SCI has developed significantly. Steroids are thought to provide neuroprotection in patients with acute SCI by improving perfusion, reducing edema, modulating inflammatory cells, and inhibiting lipid peroxidation, leading to their widespread application in clinical medicine. The use of steroids for SCI is controversial because of limited clinical evidence. With the accumulation of evidence on the effectiveness of steroid treatment in improving neurological function and the evidence of severe side effects, a gradual change in the treatment of SCI with steroids has become inevitable. Most scholars have focused on the routine use of steroids because of the indefinite improvement in neurological function and the occurrence of severe adverse events. Therefore, this review aims to provide an overview of the mechanism, progress, and related controversies to comprehensively understand the value and future direction of steroid application in acute SCI.
Topics: Humans; Spinal Cord Injuries; Steroids; Edema; Spinal Cord
PubMed: 37458661
DOI: 10.26355/eurrev_202307_32966 -
Blood Advances Jun 2023Gain-of-function mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by...
Gain-of-function mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by high reticulocyte count, a tendency to macrocytosis, and mild jaundice, as well as by other variably penetrant clinical features, such as perinatal edema, severe thromboembolic complications after splenectomy, and hepatic iron overload. PIEZO1 mutations in DHS lead to slowed inactivation kinetics of the ion channel and/or facilitation of channel opening in response to physiological stimuli. To characterize the alterations of red blood cell proteome in patients with mutated PIEZO1, we used a differential approach to compare the proteome of patients with DHS (16 patients from 13 unrelated ancestries) vs healthy individuals. We identified new components in the regulation of the complex landscape of erythrocytes ion and volume balance mediated by PIEZO1. Specifically, the main impaired processes in patients with DHS were ion homeostasis, transmembrane transport, regulation of vesicle-mediated transport, and the proteasomal catabolic process. Functional assays demonstrated coexpression of PIEZO1 and band 3 when PIEZO1 was activated. Moreover, the alteration of the vesicle-mediated transport was functionally demonstrated by an increased vesiculation rate in patients with DHS compared with healthy controls. This finding also provides an explanation of the pathogenetic mechanism underlying the increased thrombotic rate observed in these patients. Finally, the newly identified proteins, involved in the intracellular signaling pathways altered by PIEZO1 mutations, could be used in the future as potential druggable targets in DHS.
Topics: Pregnancy; Female; Humans; Gain of Function Mutation; Anemia, Hemolytic, Congenital; Proteome; Hydrops Fetalis; Erythrocytes; Mutation; Ion Channels
PubMed: 36595486
DOI: 10.1182/bloodadvances.2022008673 -
International Journal of Hematology Sep 2023TAFRO syndrome is a rare systemic inflammatory disease. Its pathogenesis mainly involves excessive cytokine secretion and autoimmune dysfunction. Although its etiology...
TAFRO syndrome is a rare systemic inflammatory disease. Its pathogenesis mainly involves excessive cytokine secretion and autoimmune dysfunction. Although its etiology is unclear, some viral infections have been reported to cause it. Here, we report a case of severe systemic inflammation mimicking TAFRO syndrome that arose after COVID-19. A 61-years-old woman suffered from a continuous fever, ascites, and edema after contracting COVID-19. She developed progressive thrombocytopenia, renal failure, and elevated C-reactive protein levels. She was tentatively diagnosed with multisystem inflammatory syndrome in adults (MIS-A) and received steroid pulse therapy. However, she exhibited worsening fluid retention and progressive renal failure, which are not typical of MIS-A. A bone marrow examination showed reticulin myelofibrosis and an increased number of megakaryocytes. Although a definitive diagnosis of TAFRO syndrome was not made according to current diagnostic criteria, we determined that her symptoms were clinically consistent with those of TAFRO syndrome. Combination therapy, including steroid pulse therapy, plasma exchange, rituximab, and cyclosporine, improved her symptoms. There are pathological similarities between hyperinflammation that arises after COVID-19 and TAFRO syndrome in terms of the associated cytokine storms. COVID-19 may have triggered the development of systemic inflammation mimicking TAFRO syndrome in this case.
Topics: Humans; Adult; Female; Middle Aged; COVID-19; Systemic Inflammatory Response Syndrome; Castleman Disease; Renal Insufficiency; Edema; Steroids
PubMed: 37000328
DOI: 10.1007/s12185-023-03589-9 -
Neuro-oncology Oct 2023Brain edema is a common complication of brain metastases (BM) and associated treatment. The extent to which cytotoxic edema, the first step in the sequence that leads to...
BACKGROUND
Brain edema is a common complication of brain metastases (BM) and associated treatment. The extent to which cytotoxic edema, the first step in the sequence that leads to ionic edema, vasogenic edema, and brain swelling, contributes to radiation-induced brain edema during BM remains unknown. This study aimed to determine whether radiation-associated treatment of BM induces cytotoxic edema and the consequences of blocking the edema in preclinical models of breast-cancer brain metastases (BCBM).
METHODS
Using in vitro and in vivo models, we measured astrocytic swelling, trans-electric resistance (TEER), and aquaporin 4 (AQP4) expression following radiation. Genetic and pharmacological inhibition of AQP4 in astrocytes and cancer cells was used to assess the role of AQP4 in astrocytic swelling and brain water intake. An anti-epileptic drug that blocks AQP4 function (topiramate) was used to prevent cytotoxic edema in models of BM.
RESULTS
Radiation-induced astrocytic swelling and transient upregulation of AQP4 occurred within the first 24 hours following radiation. Topiramate decreased radiation-induced astrocytic swelling and loss of TEER in astrocytes in vitro, and acute short-term treatment (but not continuous administration), prevented radiation-induced increase in brain water content without pro-tumorigenic effects in multiple preclinical models of BCBM. AQP4 was expressed in clinical BM and breast-cancer cell lines, but AQP4 targeting had limited direct pro-tumorigenic or radioprotective effects in cancer cells that could impact its clinical translation.
CONCLUSIONS
Patients with BM could find additional benefits from acute and temporary preventive treatment of radiation-induced cytotoxic edema using anti-epileptic drugs able to block AQP4 function.
Topics: Humans; Female; Brain Edema; Topiramate; Edema; Brain; Brain Neoplasms; Aquaporin 4; Astrocytes; Breast Neoplasms
PubMed: 37053041
DOI: 10.1093/neuonc/noad070 -
Journal of Veterinary Internal Medicine 2023The prevalence and clinical characteristics of different etiologies of peripheral edema in dogs are unknown.
BACKGROUND
The prevalence and clinical characteristics of different etiologies of peripheral edema in dogs are unknown.
HYPOTHESIS/OBJECTIVES
To determine the prevalence of different etiologies of peripheral edema, describe clinical characteristics that vary among etiologies, and report survival times.
ANIMALS
Five hundred twenty-seven dogs with peripheral edema.
METHODS
Retrospective medical record review. Differences in clinical variables among etiology groups were assessed by Kruskal-Wallis testing with post hoc pairwise Dunn's testing and Chi-square testing with Monte Carlo simulation.
RESULTS
The most common etiologies of peripheral edema in dogs were vasculitis (n = 193, 37%), lymphatic/venous obstruction (LVO; 114, 22%), and hypoalbuminemia (94, 18%). Right-sided congestive heart failure (R-CHF) was uncommon (25, 5%). Edema was localized in 377 (72%) dogs and generalized in 142 (27%) dogs, and hypoalbuminemia was more likely to cause generalized edema compared to LVO or vasculitis (P < .0001). Concurrent abdominal effusion (155, 29%) was more common than pleural (77, 15%) or pericardial (12, 2%) effusion. Abdominal and pleural effusion occurred more commonly in dogs with hypoalbuminemia or R-CHF compared to LVO or vasculitis (P < .0001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Distribution of edema, concurrent cavitary effusions, and clinicopathological data can help predict the underlying etiology of peripheral edema in dogs.
Topics: Dogs; Animals; Hypoalbuminemia; Retrospective Studies; Edema; Pleural Effusion; Heart Failure; Vasculitis; Dog Diseases
PubMed: 37452610
DOI: 10.1111/jvim.16815 -
Indian Journal of Ophthalmology Oct 2023
Topics: Humans; Macular Edema; Macula Lutea; Edema
PubMed: 37787222
DOI: 10.4103/IJO.IJO_2951_22 -
Cells Jan 2024Besides visceral heterotaxia, null mouse embryos exhibit general edema and perinatal lethality. In humans, congenital chylothorax (CCT) is a frequent cause of fetal...
Besides visceral heterotaxia, null mouse embryos exhibit general edema and perinatal lethality. In humans, congenital chylothorax (CCT) is a frequent cause of fetal hydrops. In 2021, Correa and colleagues reported ultrarare compound heterozygous variants in exhibiting in two consecutive fetuses with severe hydrops, implicating a direct role of in fetal hydrops formation. Here, we performed an exome survey and identified ultrarare compound heterozygous variants in in two of the five case-parent trios with CCT. In one family, the affected carried the ultrarare missense variants c.1543G>A(p.Gly515Arg) and c.3845T>A(p.Val1282Glu). In the other family, the affected carried the ultrarare loss-of-function variant (LoF) c.863delA(p.Asn288Thrfs*3) and the ultrarare missense variant c.6549G>T(p.Gln2183His). Investigation of the variants' impact on PKD1L1 protein localization suggests the missense variants cause protein dysfunction and the LoF variant causes protein mislocalization. Further analysis of mutant mouse embryos revealed about 20% of embryos display general edema and pleural effusion at 14.5 dpc. Immunofluorescence staining at 14.5 dpc in embryos displayed both normal and massively altered lymphatic vessel morphologies. Together, our studies suggest the implication of in congenital lymphatic anomalies, including CCTs.
Topics: Animals; Female; Humans; Mice; Pregnancy; Chylothorax; Fetus; Genetic Diseases, X-Linked; Hydrops Fetalis; Membrane Proteins; Mice, Knockout
PubMed: 38247840
DOI: 10.3390/cells13020149 -
Diagnostic and Interventional Imaging Sep 2023The purpose of this study was to identify possible association between noncontrast computed tomography (NCCT)-based radiomics features of perihematomal edema (PHE) and...
PURPOSE
The purpose of this study was to identify possible association between noncontrast computed tomography (NCCT)-based radiomics features of perihematomal edema (PHE) and poor functional outcome at 90 days after intracerebral hemorrhage (ICH) and to develop a NCCT-based radiomics-clinical nomogram to predict 90-day functional outcomes in patients with ICH.
MATERIALS AND METHODS
In this multicenter retrospective study, 107 radiomics features were extracted from 1098 NCCT examinations obtained in 1098 patients with ICH. There were 652 men and 446 women with a mean age of 60 ± 12 (SD) years (range: 23-95 years). After harmonized and univariable and multivariable screening, seven of these radiomics features were closely associated with the 90-day functional outcome of patients with ICH. The radiomics score (Rad-score) was calculated based on the seven radiomics features. A clinical-radiomics nomogram was developed and validated in three cohorts. The model performance was evaluated using area under the curve analysis and decision and calibration curves.
RESULTS
Of the 1098 patients with ICH, 395 had a good outcome at 90 days. Hematoma hypodensity sign and intraventricular and subarachnoid hemorrhages were identified as risk factors for poor outcomes (P < 0.001). Age, Glasgow coma scale score, and Rad-score were independently associated with outcome. The clinical-radiomics nomogram showed good predictive performance with AUCs of 0.882 (95% CI: 0.859-0.905), 0.834 (95% CI: 0.776-0.891) and 0.905 (95% CI: 0.839-0.970) in the three cohorts and clinical applicability.
CONCLUSION
NCCT-based radiomics features from PHE are highly correlated with outcome. When combined with Rad-score, radiomics features from PHE can improve the predictive performance for 90-day poor outcome in patients with ICH.
Topics: Male; Humans; Female; Middle Aged; Aged; Retrospective Studies; Cerebral Hemorrhage; Tomography, X-Ray Computed; Hematoma; Edema
PubMed: 37179244
DOI: 10.1016/j.diii.2023.04.008 -
JNMA; Journal of the Nepal Medical... Oct 2023Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in...
UNLABELLED
Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in the background, eventually leading to multiorgan dysfunction and death. The incidence of primary amyloidosis is estimated at 5.1-12.8 cases per million, with a poor prognosis. We report a case of a 69-year male with lower back pain, shortness of breath, and anasarca diagnosed as primary systemic amyloidosis by serum-free light chain assay and kidney needle biopsy. He was started on intravenous bortezomib and dexamethasone. Though he adhered to his medications, with time he developed renal insufficiency marked by azotemia following which hemodialysis was performed. Primary systemic amyloidosis is a rare clinical condition with a very poor prognosis. Further studies are needed to understand the proper pathophysiology and treatment of the disease.
KEYWORDS
cardiomyopathies; case reports; primary amyloidosis.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Bortezomib; Renal Insufficiency; Prognosis
PubMed: 38289775
DOI: 10.31729/jnma.8297