Early arthritis and digestive diseases. A rheumatologist’s view

Peripheral arthritis is one of the most common manifestations of articular syndrome, not always associated with rheumatic diseases. Determination of its nosological affiliation and rational therapy at an early stage (early arthritis) present a complex clinical and diagnostic problem requiring an interdisciplinary approach. The review presents the differential diagnosis of early arthritis in diseases of the gastrointestinal tract such as inflammatory bowel disease, celiac disease, PPP syndrome (Pancreatitis, panniculitis and polyarthritis (PPP-) syndrome), etc., manifested by similar clinical symptoms with rheumatic diseases such as early rheumatoid arthritis and spondylitis. Most of the immuno-inflammatory diseases presented in the review are multisystemic and heterogeneous in clinical symptoms, course and outcomes. Therefore, the diagnostic process, especially in case of early arthritis with typical multisystem involvement, is comprehensive and cognitive in nature and requires the synthesis of many data that are usually not taken into account in a simple algorithm based on a set of classification criteria.

Download Full-text

«Possibilities of a unified approach to the treatment of IgE-associated respiratory diseases. Clinical Experience exchange».

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja1456 ◽

2021 ◽

Vol 18 (2) ◽

pp. 138-148

Author(s):

Olga P. Ukhanova ◽

Dmitrii V. Karamishev ◽

Kseniya A. Ryabova ◽

Fatimat Hanova

Keyword(s):

Allergic Rhinitis ◽

Respiratory Diseases ◽

Nasal Polyposis ◽

Clinical Symptoms ◽

Inflammatory Diseases ◽

Therapeutic Option ◽

Interdisciplinary Approach ◽

Systemic Corticosteroids ◽

Proven Efficacy ◽

Control Loss

Inflammatory diseases of the upper and lower respiratory airways, such as allergic rhinitis, nasal polyposis, bronchial asthma have common proinflammatory mechanisms, mediated by IgE-dependent cascade of inflammation. Concurrent existence of asthma and allergic rhinitis and/or nasal polyposis increases clinical symptoms severity, disease course aggravation and eventually disease control loss for the patient. Anti-IgE-therapy is pathogenetically justified effective and safe therapeutic option for various patient groups. Today principles of interdisciplinary approach are in practice to target upper and lower respiratory diseases management, which determines the success of biological therapy. ENT, pulmonology and allergy specialists define patient management tactics in close collaboration taking into consideration diseases manifestation. The proven efficacy and safety of оmalizumab makes this drug a universal tool to achieve IgE-associated diseases control and an alternative solution for surgical intervention and therapy with systemic corticosteroids.

Download Full-text

420. Diagnostic Utility of Chest CT scan for COVID-19, in the Early Stage of the Pandemic in Brooklyn, New York

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.614 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S277-S277

Author(s):

Rachel Gibbs ◽

Lung H Fu ◽

Michael Silver ◽

Zachary S Lockerman ◽

Monica Ghitan ◽

...

Keyword(s):

New York ◽

Ct Scan ◽

Clinical Symptoms ◽

Early Stage ◽

Medical Center ◽

Chest Ct ◽

Diagnostic Process ◽

Rt Pcr ◽

Laboratory Findings ◽

Chest Ct Scan

Abstract Background Diagnosis of coronavirus disease 2019 (COVID-19) in the early weeks of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in New York City posed unique challenges. Due to inadequate testing availability and long turnaround times, decisions on which patients to isolate were problematic. With sensitivity comparable to reverse transcription polymerase chain reaction (RT-PCR), the absence of ground glass opacities (GGOs) on chest CT scan was useful to rule out COVID-19. We evaluated the specificity of chest CT scan findings for COVID-19 along with other clinical and laboratory findings. Methods A retrospective chart review was done of 182 adult patients who were tested for SARS-CoV-2 by RT-PCR and underwent a chest CT scan while admitted to Maimonides Medical Center between March 1 to 23, 2020. Cases were defined as those with a positive RT-PCR result or who were treated for COVID-19. Negative cases were defined as those with negative RT-PCR and an alternative diagnosis confirmed by an ID physician. Beyond March 23, almost all newly admitted patients were isolated. Results There were 111 COVID-19 positive and 71 COVID-19 negative patients. Of the COVID-19 patients, 61% were male and 39% female, 56% white, 20% Hispanic, 14% black, 9% Asian, 36% Jewish, 35% had diabetes mellitus (DM), 50% had hypertension and 42% had cardiovascular disease. Clinical symptoms, signs, and laboratory values for COVID-19 positive and negative groups were not significantly different. COVID-19 patients had significantly higher BMI (p = 0.001). On chest CT scan, bilateral or unilateral, peripheral distribution and lower lobar GGOs were over 80% specific for COVID-19. The frequency of GGOs was significantly higher when chest CT scans were done during the second week of illness compared to the first week (p = 0.0195). Jewish patients were associated with higher rates of death (p = 0.0475) and underlying DM was associated with higher rates of ARDS, AKI, intubation, ICU admission and death (p < 0.05) compared to other demographic and comorbid groups. Conclusion Chest CT scan is an important component in the diagnostic process for patients with suspected COVID-19 infection, especially during the second week of symptoms. The findings may aid clinical decisions in the setting of a second surge of SARS-CoV-2. Disclosures All Authors: No reported disclosures

Download Full-text

The Increasing Impact of Translational Research in the Molecular Diagnostics of Neuromuscular Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22084274 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4274

Author(s):

Dèlia Yubero ◽

Daniel Natera-de Benito ◽

Jordi Pijuan ◽

Judith Armstrong ◽

Loreto Martorell ◽

...

Keyword(s):

Molecular Diagnosis ◽

Clinical Symptoms ◽

Neuromuscular Diseases ◽

Genomic Analysis ◽

Molecular Diagnostic ◽

Diagnostic Process ◽

Targeted Analysis ◽

Whole Exome ◽

Referral Hospitals ◽

Uncertain Significance

The diagnosis of neuromuscular diseases (NMDs) has been progressively evolving from the grouping of clinical symptoms and signs towards the molecular definition. Optimal clinical, biochemical, electrophysiological, electrophysiological, and histopathological characterization is very helpful to achieve molecular diagnosis, which is essential for establishing prognosis, treatment and genetic counselling. Currently, the genetic approach includes both the gene-targeted analysis in specific clinically recognizable diseases, as well as genomic analysis based on next-generation sequencing, analyzing either the clinical exome/genome or the whole exome or genome. However, as of today, there are still many patients in whom the causative genetic variant cannot be definitely established and variants of uncertain significance are often found. In this review, we address these drawbacks by incorporating two additional biological omics approaches into the molecular diagnostic process of NMDs. First, functional genomics by introducing experimental cell and molecular biology to analyze and validate the variant for its biological effect in an in-house translational diagnostic program, and second, incorporating a multi-omics approach including RNA-seq, metabolomics, and proteomics in the molecular diagnosis of neuromuscular disease. Both translational diagnostics programs and omics are being implemented as part of the diagnostic process in academic centers and referral hospitals and, therefore, an increase in the proportion of neuromuscular patients with a molecular diagnosis is expected. This improvement in the process and diagnostic performance of patients will allow solving aspects of their health problems in a precise way and will allow them and their families to take a step forward in their lives.

Download Full-text

FGF23, a novel muscle biomarker detected in the early stages of ALS

Scientific Reports ◽

10.1038/s41598-021-91496-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ying Si ◽

Mohamed Kazamel ◽

Michael Benatar ◽

Joanne Wuu ◽

Yuri Kwon ◽

...

Keyword(s):

Biomarker Discovery ◽

Clinical Symptoms ◽

Early Stage ◽

Fold Increase ◽

Progressive Increase ◽

Molecular Signature ◽

Muscle Membrane ◽

Sequencing Project ◽

Progressive Muscle Weakness ◽

End Stage

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.

Download Full-text

Whole brain atlas-based diffusion kurtosis imaging parameters for evaluation of minimal hepatic encephalopathy

The Neuroradiology Journal ◽

10.1177/19714009211026924 ◽

2021 ◽

pp. 197140092110269

Author(s):

Prateek Gupta ◽

Sameer Vyas ◽

Teddy Salan ◽

Chirag Jain ◽

Sunil Taneja ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Clinical Symptoms ◽

Early Stage ◽

Imaging Techniques ◽

Clinical Stage ◽

Minimal Hepatic Encephalopathy ◽

Brain Atlas ◽

Diffusion Kurtosis Imaging ◽

Whole Brain ◽

Diffusion Kurtosis

Background and purposes Minimal hepatic encephalopathy (MHE) has no recognizable clinical symptoms, but patients have cognitive and psychomotor deficits. Hyperammonemia along with neuroinflammation lead to microstructural changes in cerebral parenchyma. Changes at conventional imaging are detected usually at the overt clinical stage, but microstructural alterations by advanced magnetic resonance imaging techniques can be detected at an early stage. Materials and methods Whole brain diffusion kurtosis imaging (DKI) data acquired at 3T was analyzed to investigate microstructural parenchymal changes in 15 patients with MHE and compared with 15 age- and sex-matched controls. DKI parametric maps, namely kurtosis fractional anisotropy (kFA), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK), were evaluated at 64 white matter (WM) and gray matter (GM) regions of interest (ROIs) in the whole brain and correlated with the psychometric hepatic encephalopathy score (PHES). Results The MHE group showed a decrease in kFA and AK across the whole brain, whereas MK and RK decreased in WM ROIs but increased in several cortical and deep GM ROIs. These alterations were consistent with brain regions involved in cognitive function. Significant moderate to strong correlations (–0.52 to –0.66; 0.56) between RK, MK and kFA kurtosis metrics and PHES were observed. Conclusion DKI parameters show extensive microstructural brain abnormalities in MHE with minor correlation between the severity of tissue damage and psychometric scores.

Download Full-text

Sustained Systemic Levels of IL-6 Impinge Early Muscle Growth and Induce Muscle Atrophy and Wasting in Adulthood

Cells ◽

10.3390/cells10071816 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1816

Author(s):

Laura Pelosi ◽

Maria Grazia Berardinelli ◽

Laura Forcina ◽

Francesca Ascenzi ◽

Emanuele Rizzuto ◽

...

Keyword(s):

Plasma Levels ◽

Muscle Wasting ◽

Inflammatory Diseases ◽

Early Stage ◽

Muscle Growth ◽

Postnatal Life ◽

Stunted Growth ◽

Skeletal Muscle Wasting ◽

Potential Biomarker ◽

Muscle Homeostasis

IL-6 is a pleiotropic cytokine that can exert different and opposite effects. The muscle-induced and transient expression of IL-6 can act in an autocrine or paracrine manner, stimulating anabolic pathways associated with muscle growth, myogenesis, and with regulation of energy metabolism. In contrast, under pathologic conditions, including muscular dystrophy, cancer associated cachexia, aging, chronic inflammatory diseases, and other pathologies, the plasma levels of IL-6 significantly increase, promoting muscle wasting. Nevertheless, the specific physio-pathological role exerted by IL-6 in the maintenance of differentiated phenotype remains to be addressed. The purpose of this study was to define the role of increased plasma levels of IL-6 on muscle homeostasis and the mechanisms contributing to muscle loss. Here, we reported that increased plasma levels of IL-6 promote alteration in muscle growth at early stage of postnatal life and induce muscle wasting by triggering a shift of the slow-twitch fibers toward a more sensitive fast fiber phenotype. These findings unveil a role for IL-6 as a potential biomarker of stunted growth and skeletal muscle wasting.

Download Full-text

Abdominal irradiation increases inflammatory cytokine expression and activates NF-κB in rat ileal muscularis layer

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00094.2003 ◽

2003 ◽

Vol 285 (3) ◽

pp. G556-G565 ◽

Cited By ~ 56

Author(s):

C. Linard ◽

A. Ropenga ◽

M. C. Vozenin-Brotons ◽

A. Chapel ◽

D. Mathe

Keyword(s):

Inflammatory Cytokine ◽

Intestinal Inflammation ◽

Clinical Symptoms ◽

Early Stage ◽

Cytokine Expression ◽

Mrna Levels ◽

Activator Protein 1 ◽

Γ Irradiation ◽

Control Tissue ◽

Anti Inflammatory

The small bowel is an important dose-limiting organ in abdominal radiotherapy because irradiation can cause acute enteritis that, in turn, leads to progressively reduced motility and finally, in a later phase, to fibrosis. Because these clinical symptoms may be caused by the early stage of an inflammatory process, we characterized the radiation-induced intestinal inflammation in rats. Abdominal γ-irradiation (10-Gy) induced a cascade of inflammatory events characterized by an early (6 h after exposure) increase in IL-1β, TNF-α, and IL-6 mRNA levels in the rat ileal muscularis layer. IL-8 [a cytokine-induced neutrophil chemoattractant (CINC)] mRNA appeared later (at 3 days). The expression of TGF-β (a profibrotic cytokine) was higher in irradiated than control tissue at day 1, whereas IL-10 (an anti-inflammatory cytokine) expression vanished completely. Despite strong IL-1ra expression, the IL-1ra/IL-1β ratio, which is an indicator of inflammatory balance, was -41% at day 1 in irradiated compared with control tissue. The nuclear transcription factors NF-κB and activator protein-1 (AP-1) govern transcription of these genes, directly or indirectly. Although expression of the subunits of NF-κB (p65, p50) and AP-1 (c- fos, c- jun) did not increase, irradiation caused a rapid and persistent translocation of p65 and p50. An imbalance between proinflammatory and anti-inflammatory mediators may contribute to perpetuating intestinal inflammation, thus making it chronic.

Download Full-text

Analysis of Separability of COVID-19 and Pneumonia in Chest X-ray Images by Means of Convolutional Neural Networks

Proceedings ◽

10.3390/proceedings2020054031 ◽

2020 ◽

Vol 54 (1) ◽

pp. 31

Author(s):

Joaquim de Moura ◽

Lucía Ramos ◽

Plácido L. Vidal ◽

Jorge Novo ◽

Marcos Ortega

Keyword(s):

Neural Networks ◽

Convolutional Neural Networks ◽

Clinical Symptoms ◽

Early Stage ◽

World Health ◽

Complete Analysis ◽

Screening Process ◽

X Ray ◽

Chest X Ray ◽

Health Organization

The new coronavirus (COVID-19) is a disease that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On 11 March 2020, the coronavirus outbreak has been labelled a global pandemic by the World Health Organization. In this context, chest X-ray imaging has become a remarkably powerful tool for the identification of patients with COVID-19 infections at an early stage when clinical symptoms may be unspecific or sparse. In this work, we propose a complete analysis of separability of COVID-19 and pneumonia in chest X-ray images by means of Convolutional Neural Networks. Satisfactory results were obtained that demonstrated the suitability of the proposed system, improving the efficiency of the medical screening process in the healthcare systems.

Download Full-text

Abnormalities of EEG Microstates In Drug-Naïve, First-Episode Schizophrenia

10.21203/rs.3.rs-1042706/v1 ◽

2021 ◽

Author(s):

Qiaoling Sun ◽

Linlin Zhao ◽

Liwen Tan

Keyword(s):

Clinical Symptoms ◽

Early Stage ◽

First Episode ◽

Healthy Controls ◽

Brain Functions ◽

Class D ◽

Syndrome Scale ◽

Drug Naïve ◽

Microstate Analysis ◽

First Episode Schizophrenia

Abstract Objective: Microstate analysis is a powerful tool to probe the brain functions, and changes in microstates under electroencephalography (EEG) have been repeatedly reported in patients with schizophrenia. This study aimed to investigate the dynamics of EEG microstates in drug-naïve, first-episode schizophrenia (FE-SCH) and to test the relationship between EEG microstates and clinical symptoms.Methods: Resting-state EEG were recorded for 23 patients with FE-SCH and 23 healthy controls using a 64-channel cap. Three parameters, i.e., contribution, duration, and occurrence, of the four microstate classes were calculated. Group differences in EEG microstates and their clinical symptoms (assessed using the Positive and Negative Syndrome Scale) were analyzed.Results: Compared with healthy controls, patients with FE-SCH showed increased duration, occurrence and contribution of microstate class C and decreased contribution and occurrence of microstate class D. In addition, the score of positive symptoms in PANSS was negatively correlated with the occurrence of microstate D.Conclusions: Our findings showed abnormal patterns of EEG microstates in drug-naïve, first-episode schizophrenia, which might help distinguish individuals with schizophrenia in the early stage and develop early intervention strategies.

Download Full-text

New workflow for classification of genetic variants’ pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID)

Journal of Medical Genetics ◽

10.1136/jmedgenet-2017-105216 ◽

2018 ◽

Vol 55 (8) ◽

pp. 530-537 ◽

Cited By ~ 50

Author(s):

Marielle E Van Gijn ◽

Isabella Ceccherini ◽

Yael Shinar ◽

Ellen C Carbo ◽

Mariska Slofstra ◽

...

Keyword(s):

Clinical Significance ◽

Clinical Symptoms ◽

Inflammatory Diseases ◽

International Study ◽

Biological Drugs ◽

Link Type ◽

Expert Opinions ◽

Mutational Hotspots ◽

Almost All

BackgroundHereditary recurrent fevers (HRFs) are rare inflammatory diseases sharing similar clinical symptoms and effectively treated with anti-inflammatory biological drugs. Accurate diagnosis of HRF relies heavily on genetic testing.ObjectivesThis study aimed to obtain an experts’ consensus on the clinical significance of gene variants in four well-known HRF genes: MEFV, TNFRSF1A, NLRP3 and MVK.MethodsWe configured a MOLGENIS web platform to share and analyse pathogenicity classifications of the variants and to manage a consensus-based classification process. Four experts in HRF genetics submitted independent classifications of 858 variants. Classifications were driven to consensus by recruiting four more expert opinions and by targeting discordant classifications in five iterative rounds.ResultsConsensus classification was reached for 804/858 variants (94%). None of the unsolved variants (6%) remained with opposite classifications (eg, pathogenic vs benign). New mutational hotspots were found in all genes. We noted a lower pathogenic variant load and a higher fraction of variants with unknown or unsolved clinical significance in the MEFV gene.ConclusionApplying a consensus-driven process on the pathogenicity assessment of experts yielded rapid classification of almost all variants of four HRF genes. The high-throughput database will profoundly assist clinicians and geneticists in the diagnosis of HRFs. The configured MOLGENIS platform and consensus evolution protocol are usable for assembly of other variant pathogenicity databases. The MOLGENIS software is available for reuse at http://github.com/molgenis/molgenis; the specific HRF configuration is available at http://molgenis.org/said/. The HRF pathogenicity classifications will be published on the INFEVERS database at https://fmf.igh.cnrs.fr/ISSAID/infevers/.

Download Full-text