scholarly journals AB0994 NEW ALTERNATIVE IN THE TREATMENT OF PATIENT WITH MUTATION OF GEN LACC1

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1790.2-1790
Author(s):  
R. M. Alcobendas ◽  
C. Quintana ◽  
J. Arostegui ◽  
C. Udaondo ◽  
S. Murias Loza ◽  
...  
Keyword(s):  
Chart Review ◽  
Loss Of Function ◽  
Acute Phase Reactants ◽  
Reactive Protein ◽  
Inflammatory Parameters ◽  
Whole Exome ◽  
Multiple Treatments ◽  
Clinical Chart ◽  
Clinical Worsening

Background:Few patients have been described in the literature with mutations in the Lacasa Domain containing one (LACC1) gene. Its clinical presentation usually associates sustained systemic inflammation associated with chronic polyarticular erosive arthritis. Until now, there have been multiple treatments described to try to control the disease, however, they are generally unsuccessful in the long term.Objectives:Describe the clinical course of a patient as well as the different treatments usedMethods:Clinical chart reviewResults:Female 18-year-old born from a consanguineous Moroccan couple. Mother, brother and sister with similar conditions. She started at 3 years with fever, anemia, intense elevation of acute phase reactants and symmetric polyarthritis (knees, elbows, carps, shoulders, hands and ankles). Subsequent whole exome sequencing identified c.128_129delGT mutation in the LACC1/FAMIN gene. During the course of her illness, she has received treatment with oral, intravenous and infiltrated corticosteroid, methotrexate and etanercept, without getting adequate control of the disease. In 2016, she started treatment with tocilizumab (8 mg / kg every two weeks), obtaining an acceptable control of the disease (requiring periodic infiltrations every 2-3 months due to persistent arthritis). Nonetheless, in April 2019, she consulted for clinical worsening of the arthritis and laboratory test (C reactive protein 99.7 mg / L, erythrosedimentation rate 53 mm / h, leukocytes 13,500/µL and neutrophils 10,930/µL). At that time, she discontinued therapy with tocilizumab and started tofacitinib 5 mg every 12 hours with good evolution. Since its introduction, it has not required joint infiltration again and the inflammatory parameters (persistently elevated previously) have normalized.Conclusion:The jak kinasa inhibitors may be a treatment option in those patients with bad response to conventional therapy.References:[1]Rabionet R, Remesal A, Mensa-Vilaró A, Murías S, Alcobendas R, González-Roca E, Ruiz-Ortiz E, Antón J, Iglesias E, Modesto C, Comas D, Puig A, Drechsel O, Ossowski S, Yagüe J, Merino R, Estivill X, Arostegui JI. Biallelic loss-of-function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis. Sci Rep. 2019 Mar 14;9(1):4579Disclosure of Interests:None declared

scholarly journals Patients With a History of Idiopathic Deep Venous Thrombosis Have Long-Term Increased Levels of Inflammatory Markers and Markers of Endothelial Damage

2016 ◽  
Vol 23 (2) ◽  
pp. 124-131 ◽  
Author(s):  
Mateja Kaja Jezovnik ◽  
Jawed Fareed ◽  
Pavel Poredos
Keyword(s):  
Inflammatory Markers ◽  
High Sensitivity ◽  
Endothelial Damage ◽  
Control Group ◽  
Necrosis Factor Alpha ◽  
Reactive Protein ◽  
Inflammatory Parameters ◽  
History Of ◽  
Hemostatic Markers

Introduction: Although the role of inflammation in DVT has been investigated in different studies, there is no definite answer as to whether increased systemic inflammation is the cause or the consequence of DVT. Aim: To follow inflammatory parameters in a cohort of patients with idiopathic DVT. Methods: Out of 49 patients with an acute idiopathic DVT, which were investigated four months after an acute episode (DEVTA 1), 43 patients were included in the follow-up study investigating inflammatory markers and hemostatic markers of endothelial damage five years after an acute DVT (DEVTA 2). A control group consisted of 43 sex and age matched healthy subjects (CONTROLS). Results: The levels of inflammatory markers were significantly higher in DEVTA 2 in comparison to CONTROLS: tumor necrosis factor alpha 2.0 pg/mL (1.1-2.3) vs 1.3 pg/mL (0.8-1.9), p < .001, high sensitivity C-reactive protein 3.2 mg/L (1.5-5.2) vs 1.7 mg/L (0.9-3.0), p = .008, interleukin-6 (IL-6) 2.7 pg/mL (2.0-3.5) vs 2.1 pg/mL (1.5-2.6), p = .025, IL-8 5.0 pg/mL (3.6-7.3) vs 2.4 pg/mL (1.8-2.8), p < .001. IL-10 was significantly decreased (0.9 pg/mL (0.7-1.8) vs 1.8 (1.5-2.2), p < .001. Most of the proinflammatory markers remained elevated in the DEVTA 2 in comparison to DEVTA 1. Markers of endothelial damage were higher in DEVTA 2 in comparison to CONTROLS and higher than in DEVTA 1. Conclusion: Patients with idiopathic DVT have long-term increased inflammatory markers and markers of endothelial damage. These findings favor the hypothesis that inflammation is a cause and not merely a consequence of acute DVT.

scholarly journals Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Anurag Markanday
Keyword(s):  
Acute Phase ◽  
English Language ◽  
Biological Marker ◽  
Acute Phase Reactants ◽  
Medline Search ◽  
Reactive Protein ◽  
Guidance Strategies ◽  
Published Evidence ◽  
Meta Analyses

Abstract Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein have traditionally been used as markers for inflammation and as a measure of “sickness index” in infectious and noninfectious conditions. In the last decade, more data have become available on the wider and more specific role for these markers in the management of complex infections. This includes the potential role in early diagnosis, in differentiating infectious from noninfectious causes, as a prognostic marker, and in antibiotic guidance strategies. A better defined role for biological markers as a supplement to clinical assessment may lead to more judicious antibiotic prescriptions, and it has the potential for a long-term favorable impact on antimicrobial stewardship and antibiotic resistance. Procalcitonin as a biological marker has been of particular interest in this regard. This review examines the current published evidence and summarizes the role of various acute-phase markers in infections. A MEDLINE search of English-language articles on acute-phase reactants and infections published between 1986 and March 2015 was conducted. Additional articles were also identified through a search of references from the retrieved articles, published guidelines, systematic reviews, and meta-analyses.

scholarly journals Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer—What Can We Learn from the Hematological Experience?

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1966 ◽  
Author(s):  
Øystein Bruserud ◽  
Helene Hersvik Aarstad ◽  
Tor Henrik Anderson Tvedt
Keyword(s):  
Acute Phase ◽  
Hematological Malignancies ◽  
Phase Reaction ◽  
C Reactive Protein ◽  
Acute Phase Reactants ◽  
Reactive Protein ◽  
Inflammatory Parameters ◽  
Cell Counts ◽  
Blood Cell Counts ◽  
White Blood Cell Counts

The acute phase reaction is a systemic response to acute or chronic inflammation. The serum level of C-reactive protein (CRP) is the only acute phase biomarker widely used in routine clinical practice, including its uses for prognostics and therapy monitoring in cancer patients. Although Interleukin 6 (IL6) is a main trigger of the acute phase reactions, a series of acute phase reactants can contribute (e.g., other members in IL6 family or IL1 subfamily, and tumor necrosis factor α). However, the experience from patients receiving intensive chemotherapy for hematological malignancies has shown that, besides CRP, other biomarkers (e.g., cytokines, soluble cytokine receptors, soluble adhesion molecules) also have altered systemic levels as a part of the acute phase reaction in these immunocompromised patients. Furthermore, CRP and white blood cell counts can serve as a dual prognostic predictor in solid tumors and hematological malignancies. Recent studies also suggest that biomarker profiles as well as alternative inflammatory mediators should be further developed to optimize the predictive utility in cancer patients. Finally, the experience from allogeneic stem cell transplantation suggests that selected acute phase reactants together with specific markers of organ damages are useful for predicting or diagnosing graft versus host disease. Acute phase proteins may also be useful to identify patients (at risk of) developing severe immune-mediated toxicity after anticancer immunotherapy. To conclude, future studies of acute phase predictors in human malignancies should not only investigate the conventional inflammatory mediators (e.g., CRP, white blood cell counts) but also combinations of novel inflammatory parameters with specific markers of organ damages.

Postoperative wound infections of the spine

2003 ◽  
Vol 15 (3) ◽  
pp. 1-5 ◽  
Author(s):  
John M. Beiner ◽  
Jonathan Grauer ◽  
Brian K. Kwon ◽  
Alexander R. Vaccaro
Keyword(s):  
Nutritional Status ◽  
Clinical Symptoms ◽  
Signs And Symptoms ◽  
Wound Infections ◽  
Lumbar Surgery ◽  
Loss Of Function ◽  
C Reactive Protein ◽  
Superficial Infection ◽  
Reactive Protein

Postoperative spinal wound infections occur in 1 to 12% of patients. The rate of infection is related to the type and duration of the procedure, comorbidities, nutritional status, and various other risk factors. Antibiotic prophylactic therapy has been clearly shown to decrease the rate of infection dramatically after lumbar surgery. These infections typically manifest with signs and symptoms of wound swelling, erythema, and drainage. Laboratory-detected values such as the erythrocyte sedimentation rate and C-reactive protein can be elevated beyond what is normal for the uncomplicated postoperative course following lumbar surgery, and combined with the clinical symptoms should alert the physician to the possibility of infection. When detected, these infections should be managed aggressively with operative debridment and irrigation, including the deep subfascial layer in all cases except those with clearly demarcated superficial infection. The choice of one versus multiple debridments can be made based on the appearance of the wound, patient factors, and nutritional status. Hardware and incorporated bone graft can be left in place in the majority of cases, adding to stability. Outcomes following aggressive treatment of this complication can be excellent, with no long-term loss of function and complete eradication of the infection.

No relation between biomarkers at age 47–49 and aortic diameter after 14–19 years of follow-up – a population-based study

VASA ◽  
2017 ◽  
Vol 46 (4) ◽  
pp. 291-295 ◽  
Author(s):  
Soumia Taimour ◽  
Moncef Zarrouk ◽  
Jan Holst ◽  
Olle Melander ◽  
Gunar Engström ◽  
...  
Keyword(s):  
Population Based ◽  
Aortic Diameter ◽  
Aortic Dilatation ◽  
Population Based Study ◽  
Reactive Protein ◽  
Abdominal Aortic ◽  
Long Term Follow Up ◽  
Old Men

Abstract. Background: Biomarkers reflecting diverse pathophysiological pathways may play an important role in the pathogenesis of abdominal aortic aneurysm (aortic diameter ≥30 mm, AAA), levels of many biomarkers are elevated and correlated to aortic diameter among 65-year-old men undergoing ultrasound (US) screening for AAA. Probands and methods: To evaluate potential relationships between biomarkers and aortic dilatation after long-term follow-up, levels of C-reactive protein (CRP), proneurotensin (PNT), copeptin (CPT), lipoprotein-associated phospholipase 2 (Lp-PLA2), cystatin C (Cyst C), midregional proatrial natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM) were measured in 117 subjects (114 [97 %] men) aged 47–49 in a prospective population-based cohort study, and related to aortic diameter at US examination of the aorta after 14–19 years of follow-up. Results: Biomarker levels at baseline did not correlate with aortic diameter after 14–19 years of follow up (CRP [r = 0.153], PNT [r = 0.070], CPT [r = –.156], Lp-PLA2 [r = .024], Cyst C [r = –.015], MR-proANP [r = 0.014], MR-proADM [r = –.117]). Adjusting for age and smoking at baseline in a linear regression model did not reveal any significant correlations. Conclusions: Tested biomarker levels at age 47–49 were not associated with aortic diameter at ultrasound examination after 14–19 years of follow-up. If there are relationships between these biomarkers and aortic dilatation, they are not relevant until closer to AAA diagnosis.

Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia

2020 ◽  
Author(s):  
Yousef Binamer ◽  
Muzamil A. Chisti
Keyword(s):  
Autosomal Recessive ◽  
Common Mechanism ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Skin Atrophy ◽  
Whole Exome ◽  
Infancy And Childhood ◽  
Genetics And Genomics ◽  
New Feature ◽  
Generation Sequencing

AbstractKindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of FERMT1 in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

Autosomal Recessive Non-syndromic Keratoconus: Homozygous Frameshift Variant in the Candidate Novel Gene GALNT14

2019 ◽  
Vol 19 (9) ◽  
pp. 683-687 ◽  
Author(s):  
Tawfiq Froukh ◽  
Ammar Hawwari
Keyword(s):  
Strong Evidence ◽  
Autosomal Recessive ◽  
Eye Diseases ◽  
Initial Reaction ◽  
Genetic Contribution ◽  
Loss Of Function ◽  
Consanguineous Family ◽  
Truncated Protein ◽  
Threonine Residue ◽  
Whole Exome

Background: Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases. Methods: In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene. Result: GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins. Conclusion: As alterations of mucin’s glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.

Identification of WDFY3 Neoantigens as Prognostic Markers in Longterm Survivors of Extrahepatic Cholangiocarcinoma

2020 ◽  
Vol 20 (11) ◽  
pp. 875-886
Author(s):  
Yingyi Wang ◽  
Bao Jin ◽  
Na Zhou ◽  
Zhao Sun ◽  
Jiayi Li ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Prognostic Markers ◽  
Immune Cell ◽  
Neutrophil Infiltration ◽  
Computational Biophysics ◽  
Extrahepatic Cholangiocarcinoma ◽  
Whole Exome ◽  
Mutation Burden ◽  
Long Term Survivors

Background:: Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined. Objective: The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival. Methods: We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry. Results: : Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration. Conclusion:: We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.

scholarly journals Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe fucosidosis: A case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Xinwen Zhang ◽  
Shaozhi Zhao ◽  
Hongwei Liu ◽  
Xiaoyan Wang ◽  
Xiaolei Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Signs And Symptoms ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Exon 1

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

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