Endotrophin and C6Ma3, serological biomarkers of type VI collagen remodelling, reflect endoscopic and clinical disease activity in IBD

AbstractIn inflammatory bowel disease (IBD), the chronic inflammation deeply affects the intestinal extracellular matrix. The aim of this study was to investigate if remodeling of the intestinal basement membrane type VI collagen was associated with pathophysiological changes in Crohn’s disease (CD) and ulcerative colitis (UC). Serum from IBD patients (CD: n = 65; UC: n = 107; irritable bowel syndrome: n = 18; healthy subjects: n = 20) was investigated in this study. The serological biomarkers C6Ma3 (a matrix metalloproteinase (MMP) generated fragment of the type VI collagen α3 chain) and PRO-C6, also called endotrophin (the C-terminus of the released C5 domain of the type VI collagen α3 chain) were measured by ELISAs. Serum C6Ma3 was increased in CD patients with moderate to severe and mild endoscopically active disease compared to endoscopic remission (p = 0.002, p = 0.0048), respectively, and could distinguish endoscopically active disease from remission with an AUC of 1.0 (sensitivity: 100%, specificity: 100%) (p < 0.0001), which was superior to CRP. C6Ma3 was increased in CD patients with moderate to severe clinical disease compared to mild and remission (p = 0.04; p = 0.009). Serum PRO-C6, endotrophin, was increased in CD patients in clinically remission compared to mild disease (p = 0.04) and moderate to severe disease (p = 0.065). In UC, fecal calprotectin was the only marker that alone could distinguish both clinical and endoscopic active and inactive disease. Type VI collagen degradation of the α3 chain mediated by MMPs was increased in CD patients with endoscopically active disease, measured by the serological biomarker C6Ma3, which was able to distinguish endoscopically active from inactive CD.

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FECAL CALPROTECTIN: levels for the ethiological diagnosis in Brazilian patients with gastrointestinal symptoms

Arquivos de Gastroenterologia ◽

10.1590/s0004-28032015000100011 ◽

2015 ◽

Vol 52 (1) ◽

pp. 50-54 ◽

Cited By ~ 8

Author(s):

Lorete Maria da Silva KOTZE ◽

Renato Mitsunori NISIHARA ◽

Sandra Beatriz MARION ◽

Murilo Franco CAVASSANI ◽

Paulo Gustavo KOTZE

Keyword(s):

Ulcerative Colitis ◽

Irritable Bowel Syndrome ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Inflammatory Bowel Diseases ◽

Fecal Calprotectin ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Irritable Bowel ◽

Active Disease

Background Determination of fecal calprotectin can provide an important guidance for the physician, also in primary care, in the differential diagnosis of gastrointestinal disorders, meanly between inflammatory bowel diseases and irritable bowel syndrome. Objectives The aims of the present study were to prospectively investigate, in Brazilian adults with gastrointestinal complaints, the value of fecal calprotectin as a biomarker for the differential diagnosis between functional and organic disorders and to correlate the concentrations with the activity of inflammatory bowel diseases. Methods The study included consecutive patients who had gastrointestinal complaints in which the measurement levels of fecal calprotectin were recommended. Fecal calprotectin was measured using a Bühlmann (Basel, Switzerland) ELISA kit Results A total of 279 patients were included in the study, with median age of 39 years (range, 18 to 78 years). After clinical and laboratorial evaluation and considering the final diagnosis, patients were allocated into the following groups: a) Irritable Bowel Syndrome: 154 patients (102 female and 52 male subjects). b) Inflammatory Bowel Diseases group: 112 patients; 73 with Crohn’s disease; 38 female and 35 male patients; 52.1% (38/73) presented active disease, and 47.9% (35/73) had disease in remission and 39 patients with ulcerative colitis;19 female and 20 male patients; 48.7% (19/39) classified with active disease and 49.3% (20/39) with disease in remission. A significant difference (P<0.001) was observed between the median value of fecal calprotectin in Irritable Bowel Syndrome group that was 50.5 µg/g (IQR=16 - 294 µg/g); 405 µg/g (IQR=29 - 1980 µg/g) in Crohn’s disease patients and 457 µg/g (IQR=25 - 1430 µg/g) in ulcerative colitis patients. No difference was observed between the values found in the patients with Crohn’s disease and ulcerative colitis. Levels of fecal calprotectin were significantly lower in patients with inflammatory bowel diseases in remission when compared with active disease (P<0.001). Conclusions The present study showed that the determination of fecal calprotectin assists to differentiate between active and inactive inflammatory bowel diseases and between inflammatory bowel diseases and irritable bowel syndrome.

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Clinical influence of maternal serum homocysteine, folate and vitamin B12 in the development of pre-eclampsia

Pteridines ◽

10.1515/pteridines-2019-0006 ◽

2019 ◽

Vol 30 (1) ◽

pp. 48-53 ◽

Cited By ~ 1

Author(s):

Hongyan Zhao ◽

Xu Zeng

Keyword(s):

Vitamin B12 ◽

Gestational Hypertension ◽

Severe Disease ◽

Serum Levels ◽

Maternal Serum ◽

Control Group ◽

Mild Disease ◽

Serum Homocysteine ◽

Folate And Vitamin B12 ◽

Serological Biomarkers

Abstract Background: The aim of this study was to investigate the correlation between maternal serum homocysteine (Hcy), folate, vitamin B12 (VitB12) and the development of pre-eclampsia (PE). Methods: Seventy-eight normal pregnant women (without hypertension and proteinuria during their pregnancy (control group)), 66 cases of gestational hypertension (GH group) and 82 cases of pre-eclampsia (PE group, with 56 cases of mild disease and 26 cases of severe disease) were include in this study. The maternal serum Hcy, folate and VitB12 level of the included cases were examined between 11 to 13 weeks gestation and compared between each group. Results: The serum levels of VitB12 were significantly different between the control, GH and PE groups (p<0.05). The serum levels of Hcy in the PE group were significantly higher than those of the control group (p<0.05). However, the serum levels of folate in the PE group were significantly lower than those of control group (p<0.05). Significant statistical differences in the maternal serum Hcy and folate were found between mild and severe PE patient groups (p<0.05). A significant correlation was found between maternal serum Hcy and VitB12 (r=-0.34, p=0.001). Conclusion: Hcy, folate and VitB12 may play an important role in the development of PE and could be potential serological biomarkers for early PE diagnosis.

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Follow-up of COVID-19 recovered patients with mild disease

Scientific Reports ◽

10.1038/s41598-021-92717-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alina Kashif ◽

Manahil Chaudhry ◽

Tehreem Fayyaz ◽

Mohammad Abdullah ◽

Ayesha Malik ◽

...

Keyword(s):

Severe Disease ◽

Female Gender ◽

Sample Population ◽

Mild Disease ◽

Fatigue Syndrome ◽

Active Disease

AbstractCOVID-19 may manifest as mild, moderate or severe disease with each grade of severity having its own features and post-viral implications. With the rising burden of the pandemic, it is vital to identify not only active disease but any post-recovery complications as well. This study was conducted with the aim of identifying the presence of post-viral symptomatology in patients recovered from mild COVID-19 disease. Presence or absence of 11 post-viral symptoms was recorded and we found that 8 of the 11 studied symptoms were notably more prevalent amongst the female sample population. Our results validate the presence of prolonged symptoms months after recovery from mild COVID-19 disease, particularly in association with the female gender. Hence, proving the post-COVID syndrome is a recognizable diagnosis in the bigger context of the post-viral fatigue syndrome.

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THU0349 THE RELATIONSHIP BETWEEN DISEASE ACTIVITY AND SEVERITY IN SYSTEMIC SCLEROSIS: A PROSPECTIVE ANALYSIS OF 278 PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6129 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 406.2-406

Author(s):

Y. Yalçinkaya ◽

N. Aliyeva ◽

S. Amikishiyev ◽

Y. Cagatay ◽

B. Artim-Esen ◽

...

Keyword(s):

Systemic Sclerosis ◽

Disease Activity ◽

Severe Disease ◽

Inactive Disease ◽

Prospective Analysis ◽

Peripheral Vascular ◽

Cutaneous Involvement ◽

Severity Scores ◽

The Relationship ◽

Active Disease

Background:Evaluating disease activity and severity in systemic sclerosis (SSc) is crucial to define the patients who are candidate for treatment options.Objectives:We aimed to investigate the relationship between disease activity and severity in SSc in a large cohort.Methods:This is a cross-sectional prospective analysis of 278 (253 females) patients fulfilling ACR/EULAR (2013) classification criteria for SSc. Disease activity and severity were calculated seperately for cutaneous subsets (EscSG and Medsger). The patients were grouped as inactive if EscSG score=0, mildly active if EscSG score>0<3, active if EscSG score≥3.Results:The mean age, duration of Raynaud’s and non-Raynaud features were 48.5±13.1, 12.1±9.8 and 8.3±7.5 years respectively. Characteristics of the SSc patients were summarized in table-1.Ninety-three (34%) and 151(54%) patients were evaluated as having active and mildly active disease. Only 34(12%) patients had inactive disease. The patients with diffuse cutaneous involvement (dcSSc) who were active had higher modified Rodnan Skin score(mRSS) and severity scores of general, skin and joint-tendon involvements; the patients who had mildly active disease also had higher scores of mRSS and severity scores of skin compared to those with inactive disease (table-2).The patients with limited cutaneous involvement (lcSSc) who were assessed as having active disease had higher mRSS and higher severity scores of general, skin, peripheral vascular, lung, joint-tendon and gastrointestinal involvements; the patients who had mildly active disease also had higher scores of mRSS and severity scores of skin, lung, joint-tendon and gastrointestinal involvements compared to those with inactive disease (table-2).Conclusion:One third of our cohort was found to have active disease despite treatment and only 12% had inactive disease. Skin involvement and severity of different organs were shown to be higher in patients with active disease in both cutaneous subsets, together with severity of lung, peripheral vascular and gastrointestinal involvements in active lcSSc. LcSSc and dcSSc patients who had mildly active disease also had severe disease similar to those with active patients. Disease activity and severity should be assessed as separate measurements to highlight the course of the disease and may guide to the management of patients with SSc.Disclosure of Interests:None declared

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Follow-up of COVID-19 Recovered Patients with Mild Disease

10.21203/rs.3.rs-120819/v1 ◽

2021 ◽

Author(s):

Alina Kashif ◽

Manahil Chaudhry ◽

Tehreem Fayyaz ◽

Mohammad Abdullah ◽

Ayesha Malik ◽

...

Keyword(s):

Severe Disease ◽

Female Gender ◽

Sample Population ◽

Mild Disease ◽

Fatigue Syndrome ◽

Active Disease

Abstract COVID-19 may manifest as mild, moderate or severe disease with each grade of severity having its own features and post-viral implications. With the rising burden of the pandemic, it is vital to identify not only active disease but any post-recovery complications as well.This study was conducted with the aim of identifying the presence of post-viral symptomatology in patients recovered from mild COVID-19 disease. Presence or absence of eleven post viral symptoms was recorded and we found that eight of the eleven studied symptoms were notably more prevalent amongst the female sample population. Our results validate the presence of prolonged symptoms months after recovery from mild COVID-19 disease, particularly in association with the female gender. Hence, proving the post-COVID syndrome is a recognizable diagnosis in the bigger context of the post-viral fatigue syndrome.

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K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia

10.1101/2020.08.07.242073 ◽

2020 ◽

Cited By ~ 3

Author(s):

Jian Zheng ◽

Lok-Yin Roy Wong ◽

Kun Li ◽

Abhishek K. Verma ◽

Miguel Ortiz ◽

...

Keyword(s):

Severe Disease ◽

Severe Pneumonia ◽

Clinical Disease ◽

Morbidity And Mortality ◽

Therapeutic Interventions ◽

Mild Disease ◽

Common Presentation ◽

Experimental Infections ◽

The Brain ◽

Substantial Morbidity

ABSTRACTThe ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.

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SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.801 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1227.3-1228

Author(s):

M. E. Tezcan ◽

N. Şen ◽

M. Yilmaz ◽

Ö. Volkan ◽

E. Tükel ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Scoring System ◽

Disease Duration ◽

Severe Disease ◽

Smoking History ◽

Disease Group ◽

Severity Scoring ◽

Mild Disease ◽

Co Morbidity ◽

Mediterranean Fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

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A Case Series of SARS-CoV-2 RT-PCR-Positive Hospitalized Infants 60 Days of Age or Younger From 2 New York City Pediatric Emergency Departments

Clinical Pediatrics ◽

10.1177/00099228211006688 ◽

2021 ◽

Vol 60 (4-5) ◽

pp. 247-251

Author(s):

Ameer Hassoun ◽

Nessy Dahan ◽

Christopher Kelly

Keyword(s):

New York ◽

Case Reports ◽

Severe Disease ◽

Case Series ◽

Pediatric Emergency ◽

Rt Pcr ◽

Vulnerable Group ◽

Mild Disease ◽

Young Infants ◽

Novel Coronavirus

The emergence of novel coronavirus disease-2019 poses an unprecedented challenge to pediatricians. While the majority of children experience mild disease, initial case reports on young infants are conflicting. We present a case series of 8 hospitalized infants 60 days of age or younger with coronavirus disease-2019. A quarter of these patients had coinfections (viral or bacterial). None of these infants had severe disease. Continued vigilance in testing this vulnerable group of infants is warranted.

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SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

Journal of Personalized Medicine ◽

10.3390/jpm11050431 ◽

2021 ◽

Vol 11 (5) ◽

pp. 431

Author(s):

Sabine Hofer ◽

Norbert Hofstätter ◽

Albert Duschl ◽

Martin Himly

Keyword(s):

Risk Factor ◽

Particle Deposition ◽

Early Stage ◽

Severe Disease ◽

Ambient Air ◽

Aerosol Deposition ◽

Pulmonary Involvement ◽

Mild Disease ◽

Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

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Outpatient Management of COVID-19 Disease: A Holistic Patient-Centered Proposal Based on the Greek Experience

Journal of Personalized Medicine ◽

10.3390/jpm11080709 ◽

2021 ◽

Vol 11 (8) ◽

pp. 709

Author(s):

Adamantia Liapikou ◽

Eleni Tzortzaki ◽

Georgios Hillas ◽

Miltiadis Markatos ◽

Ilias C. Papanikolaou ◽

...

Keyword(s):

Preventive Measures ◽

Severe Disease ◽

Hospital Setting ◽

Guidance Document ◽

Outpatient Management ◽

Patient Centered ◽

Mild Disease ◽

Novel Coronavirus ◽

Second Wave ◽

Close Contacts

Novel coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic and affected more than 227 countries or territories, resulting in more than 179 million cases with over 3.890.00 deaths, as of June 25, 2021. The Hellenic Thoracic Society (HTS) during the second wave of COVID-19 pandemic released a guidance document for the management of patients with COVID-19 in the community and in hospital setting. In this review, with guidance the HTS document, we are discussing the outpatient management of COVID-19 patients, including the preventive measures, the patients’ isolation and quarantine criteria of close contacts, the severity and risk stratification, including the decisions for advanced hospitalization, and the disease management at home in patients with mild disease and after hospital discharge for those with more severe disease.

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