Comparison of Characteristics and Laboratory Tests of COVID 19-Hematological Patients from France and Brazil: Identification of Prognostic Driven Profiles

Abstract Background: The COVID-19 disease has spread throughout the world in an unprecedented way. France and Brazil confirmed the first cases in the European and South American regions with high incidence rates at the peak of the first wave of contamination along the year 2020. Patients with hematological disorders, especially malignancies, may be more vulnerable to SARS-CoV-2 infection because of the underlying disease and treatment. Since COVID-19 presentation is heterogeneous, from asymptomatic up to severe life-threatening forms and the patients with malignancies and COVID-19 admitted to the hospital show a wide range of clinical manifestations and laboratory abnormalities, it is still unclear for clinicians which patients, blood tests at admission and disease factors are associated with worse outcomes. Getting further insights into patients with specific diseases is of particular interest. We aimed to identify profiles of hematologic patients hospitalized with COVID-19 that would be associated with survival, and to assess the differences between cohorts. Methods: A binational cohort including all consecutive hematological patients aged 18 years or more with moderate or severe COVID-19, requiring hospitalization until December 2020 at two tertiary centers, from Paris, France and São Paulo, Brazil, was studied. Patients with a hospital stay of less than 24 hours were excluded. All patients were followed until the end of hospitalization; then, after discharge, survival data was recovered on medical charts or outpatient consultations, if data were available. Patient profiles were based on age, comorbidities, blood tests at admission, COVID-19 symptoms, and hematological disease characteristics. A semi-supervised learning method was first used to obtain the prognostic driven profiles; then, a classifier was identified to allow the classification of patients using only admission (baseline) data. Results: A total of 263 patients (135 from Brazil and 128 from France) were enrolled. Male patients (58.2%), elderly (≥ 65 years, 46%), with high comorbidities prevalence were frequent. Non-Hodgkin Lymphoma (29.3%), multiple myeloma (19.4%) and chronic myeloid disorders (12.9%) were the most frequent underlying hematological malignancies and 13.3% of patients had benign diseases. Most of the patients (59.7%) had undergone chemotherapy in the last six months before COVID-19 admission. The clinical presentation of COVID-19 was similar in the two countries. Fever (68.4%), dyspnea (60.1%) and cough (55.9%) were the main symptoms at admission. The ICU admission (56% versus 25%) and invasive ventilation (42% versus 19%) rates were notably higher among Brazilian patients due to scarce ICU beds during the peak of transmission in France. The overall in-hospital mortality rate was 115/263 (43.7% [95%CI 37.6-49.9]) and the median follow-up after admission was 63 days (IQR 40-98). There was no evidence of survival difference between countries after adjusting on age, comorbidities, and diagnosis. Two clusters were identified, segregating young patients with few comorbidities, low CRP, D-dimers, LDH and creatinine levels, with a 30-day survival of 77.1%, versus 46.7% in remainders. The profiles (clusters) were strongly associated with survival (p<0.001), even after adjusting on age (p<0.001) (Figure 1). We identified a set of rules to classify patients into the two profiles, using only information available at hospital admission, with a high accuracy rate (97.7% on the training set and 84.9% on the validation set). The baseline predictors consecutively selected by the model were the number of comorbidities, creatinine, CRP, a continuous regimen of chemotherapy, platelets and lymphocytes counts, a symptom of ageusia, dyspnea, hematological malignancy, high blood pressure, and symptom of myalgia. Conclusions: This analysis allowed to identify two profiles of hospitalized hematological patients with COVID-19 that have a different outcome when infected with SARS-CoV-2. The results showed the importance of CRP, LHD, and creatinine in COVID-19 presentation and prognosis, whatever the geographic origin of the patients. The identification of patterns and clinical manifestations experienced by hematological patients during moderate or severe SARS-CoV-2 infection might be helpful to medical staff in the care management and in the allocation of scarce resources. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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MANAGEMENT OF YOUNG PATIENTS WITH MARFAN SYNDROME

Российский педиатрический журнал ◽

10.18821/1560-9561-2019-22-6-395-400 ◽

2019 ◽

Vol 22 (6) ◽

pp. 395-400

Author(s):

Ekaterina B. Luneva ◽

E. G. Malev

Keyword(s):

Marfan Syndrome ◽

Beta Blockers ◽

Angiotensin Receptor Blockers ◽

Relevant Literature ◽

Age Groups ◽

Young Patients ◽

Clinical Manifestations ◽

Wide Range ◽

Receptor Blockers ◽

Musculoskeletal Systems

Marfan syndrome is a hereditary, autosomal disease with a relatively high prevalence in the general population. Numerous manifestations of Marfan syndrome are expressed in a wide range of disorders involving cardiovascular, ocular and musculoskeletal systems. The article describes the principles of management of the syndrome in children and adolescents. Clinical manifestations of the disease are evaluated in young patients of different age groups. There are presented data on the main medicines used in the therapy of Marfan syndrome, such as beta-blockers, angiotensin receptor blockers, statins. Relevant literature was searched using the databases PubMed, MedLine, Scopus, Web of Science. The article will be interesting to a wide range of specialists: pediatricians, cardiologists, general practitioners and other specialties

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General Overview of Nontuberculous Mycobacteria Opportunistic Pathogens: Mycobacterium avium and Mycobacterium abscessus

Journal of Clinical Medicine ◽

10.3390/jcm9082541 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2541 ◽

Cited By ~ 1

Author(s):

Kimberly To ◽

Ruoqiong Cao ◽

Aram Yegiazaryan ◽

James Owens ◽

Vishwanath Venketaraman

Keyword(s):

Pulmonary Disease ◽

Mycobacterium Avium ◽

Nontuberculous Mycobacteria ◽

Clinical Manifestations ◽

Developed Countries ◽

Incidence Rates ◽

Mycobacterium Abscessus ◽

Human Pathogens ◽

General Overview ◽

Wide Range

Nontuberculous mycobacteria (NTM) are emerging human pathogens, causing a wide range of clinical diseases affecting individuals who are immunocompromised and who have underlying health conditions. NTM are ubiquitous in the environment, with certain species causing opportunistic infection in humans, including Mycobacterium avium and Mycobacterium abscessus. The incidence and prevalence of NTM infections are rising globally, especially in developed countries with declining incidence rates of M. tuberculosis infection. Mycobacterium avium, a slow-growing mycobacterium, is associated with Mycobacterium avium complex (MAC) infections that can cause chronic pulmonary disease, disseminated disease, as well as lymphadenitis. M. abscessus infections are considered one of the most antibiotic-resistant mycobacteria and are associated with pulmonary disease, especially cystic fibrosis, as well as contaminated traumatic skin wounds, postsurgical soft tissue infections, and healthcare-associated infections (HAI). Clinical manifestations of diseases depend on the interaction of the host’s immune response and the specific mycobacterial species. This review will give a general overview of the general characteristics, vulnerable populations most at risk, pathogenesis, treatment, and prevention for infections caused by Mycobacterium avium, in the context of MAC, and M. abscessus.

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Phenotype-Genotype Spectrum of Stomatocytic Disorders Encountered in India Using Next Generation Sequencing

Blood ◽

10.1182/blood-2018-99-114554 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2326-2326

Author(s):

Reena Das ◽

Manu Jamwal ◽

Anu Aggarwal ◽

Prashant Sharma ◽

Arindam Maitra ◽

...

Keyword(s):

G6pd Deficiency ◽

Sanger Sequencing ◽

Conflicts Of Interest ◽

Clinical Manifestations ◽

In Silico Analysis ◽

Autosomal Recessive Inheritance ◽

Pathogenic Mutation ◽

Phenotypic Correlation ◽

Red Cell Membrane ◽

Wide Range

Abstract Introduction Stomatocytes in peripheral blood are pathognomonic findings in multiple conditions along with hemolysis and reticulocytosis, often suggestive of erythrocyte membrane transport defects. These uncommon disorders are usually difficult to diagnose due to a wide range of overlapping phenotypes and a perception of stomatocytes being artefacts. Genes involved in these disorders are multiple (RHAG,SLC4A1, ABCG5, ABCG8, PIEZO1,KCNN4, ABCB6, SLC2A1 etc) rendering Sanger sequencing costly and labor intensive. Phenotypes vary from transfusion-dependent anemia to compensated hemolysis. Methods Seventeen patients were encountered in 12 families and enrolled in this study. Majority of the cases showed the presence of significant numbers of red blood cells showing stomatocytes with or without thrombocytopenia. Various hematological, biochemical and molecular tests were used to exclude thalassemia syndromes and hemoglobinopathies, glucose-6-phosphate dehydrogenase (G6PD) deficiency, autoimmune hemolytic anemia, hereditary spherocytosis (HS) and pyruvate kinase deficiency. Genomic DNA was extracted by the QIAamp DNA Blood Midi Kit and quantified on NanoDrop 2000 spectrophotometer and QubitFluorometer. DNA libraries were prepared using Illumina's custom panels (TruSight One Sequencing Panel and TruSeq Custom Amplicon v1.5) and sequenced on a MiSeq Sequencing System. MiSeq Reporter and VariantStudio were used for analysis, classification, and reporting of variants. Variants which were predicted pathogenic by in silico analysis using PolyPhen-2, SIFT, PROVEAN (http://provean.jcvi.org/), Mutpred (http://mutpred.mutdb.org/) and Human Splicing Finder as indicated, were subjected to Sanger sequencing in the patient and family members (where available). Results Of these 17 patients, 10 patients in 6 families were diagnosed to have Mediterranean stomatocytosis/ macrothrombocytopenia. All had the presence of stomatocytes along with macrothrombocytopenia, short stature, continuous abdominal discomfort and marked pleiotropic effects in different cases. This is a syndromic form of stomatocytosis and defects in ABCG5/ABCG8 genes were found and showed an autosomal recessive inheritance pattern. One case did not show any mutation. This number of cases suggests that this disorder is not rare in India and is probably underdiagnosed as patients have mild or moderate anemia and are often misdiagnosed as cases with HS. One of the patients also had coinheritance of G6PD deficiency (G6PD Kerela Kalyan). Patients with Mediterranean stomatocytosis/macrothrombocytopenia are advised to take sterol-absorption inhibitor 'ezetimibe' to reduce sterol accumulation. We also found 2 unrelated patients with stomatocytosis, reticulocytosis and splenomegaly with overhydrated hereditary stomatocytosis (OHSt) and pathogenic mutation in RHAG gene was found in both of them. The pattern of inheritance is sporadic or autosomal dominant. Splenectomy was deferred in a patient with OHSt as postsplenectomy thrombotic complications are known to occur and is contraindicated. Four patients in 3 families were found to have mutations in PIEZO1 gene which translates to red cell membrane mechanosensitive cation channel protein, causing xerocytosis/dehydrated hereditary stomatocytosis and 3 patients had severe anemia and were transfusion dependent. One patient showed the presence of stomatocytes and macrothrombocytopenia was found to have probably disease causing variant in SLC2A1 gene. She was incidentally undergoing treatment for infertility when the stomatocytosis was noted. Conclusions Stomatocytic disorders appear to be underdiagnosed in India which is compounded by the protean clinical manifestations, milder phenotypes, low index of suspicion and non-availability of molecular confirmation. Astute phenotype characterization is critical as it will help in establishing the causality of the variants identified and appropriate genetic counseling. Recently NGS for hemolytic anemias has led to rapid molecular characterization and accurate phenotypic correlation. Disclosures No relevant conflicts of interest to declare.

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Search for mutations of the interferon-induced transmembrane protein 5 (IFITM5) gene in patients with osteogenesis imperfecta

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2019.10.21-29 ◽

2019 ◽

pp. 21-29

Author(s):

А.Р. Зарипова ◽

Л.Р. Нургалиева ◽

А.В. Тюрин ◽

И.Р. Минниахметов ◽

Р.И. Хусаинова

Keyword(s):

Osteogenesis Imperfecta ◽

De Novo ◽

Transmembrane Protein ◽

Clinical Signs ◽

Clinical Manifestations ◽

Heterozygous Mutation ◽

Type I ◽

New Genes ◽

Wide Range ◽

Type V

Проведено исследование гена интерферон индуцированного трансмембранного белка 5 (IFITM5) у 99 пациентов с несовершенным остеогенезом (НО) из 86 неродственных семей. НО - клинически и генетически гетерогенное наследственное заболевание соединительной ткани, основное клиническое проявление которого - множественные переломы, начиная с неонатального периода жизни, зачастую приводящие к инвалидизации с детского возраста. К основным клиническим признакам НО относятся голубые склеры, потеря слуха, аномалия дентина, повышенная ломкость костей, нарушения роста и осанки с развитием характерных инвалидизирующих деформаций костей и сопутствующих проблем, включающих дыхательные, неврологические, сердечные, почечные нарушения. НО встречается как у мужчин, так и у женщин. До сих пор не определена степень генетической гетерогенности заболевания. На сегодняшний день известно 20 генов, вовлеченных в патогенез НО, и исследователи разных стран продолжают искать новые гены. В последнее десятилетие стало известно, что аутосомно-рецессивные, аутосомно-доминантные и Х-сцепленные мутации в широком спектре генов, кодирующих белки, которые участвуют в синтезе коллагена I типа, его процессинге, секреции и посттрансляционной модификации, а также в белках, которые регулируют дифференцировку и активность костеобразующих клеток, вызывают НО. Мутации в гене IFITM5, также называемом BRIL (bone-restricted IFITM-like protein), участвующем в формировании остеобластов, приводят к развитию НО типа V. До 5% пациентов имеют НО типа V, который характеризуется образованием гиперпластического каллуса после переломов, кальцификацией межкостной мембраны предплечья и сетчатым рисунком ламелирования, наблюдаемого при гистологическом исследовании кости. В 2012 г. гетерозиготная мутация (c.-14C> T) в 5’-нетранслируемой области (UTR) гена IFITM5 была идентифицирована как основная причина НО V типа. В представленной работе проведен анализ гена IFITM5 и идентифицирована мутация c.-14C>T, возникшая de novo, у одного пациента с НО, которому впоследствии был установлен V тип заболевания. Также выявлены три известных полиморфных варианта: rs57285449; c.80G>C (p.Gly27Ala) и rs2293745; c.187-45C>T и rs755971385 c.279G>A (p.Thr93=) и один ранее не описанный вариант: c.128G>A (p.Ser43Asn) AGC>AAC (S/D), которые не являются патогенными. В статье уделяется внимание особенностям клинических проявлений НО V типа и рекомендуется определение мутации c.-14C>T в гене IFITM5 при подозрении на данную форму заболевания. A study was made of interferon-induced transmembrane protein 5 gene (IFITM5) in 99 patients with osteogenesis imperfecta (OI) from 86 unrelated families and a search for pathogenic gene variants involved in the formation of the disease phenotype. OI is a clinically and genetically heterogeneous hereditary disease of the connective tissue, the main clinical manifestation of which is multiple fractures, starting from the natal period of life, often leading to disability from childhood. The main clinical signs of OI include blue sclera, hearing loss, anomaly of dentin, increased fragility of bones, impaired growth and posture, with the development of characteristic disabling bone deformities and associated problems, including respiratory, neurological, cardiac, and renal disorders. OI occurs in both men and women. The degree of genetic heterogeneity of the disease has not yet been determined. To date, 20 genes are known to be involved in the pathogenesis of OI, and researchers from different countries continue to search for new genes. In the last decade, it has become known that autosomal recessive, autosomal dominant and X-linked mutations in a wide range of genes encoding proteins that are involved in the synthesis of type I collagen, its processing, secretion and post-translational modification, as well as in proteins that regulate the differentiation and activity of bone-forming cells cause OI. Mutations in the IFITM5 gene, also called BRIL (bone-restricted IFITM-like protein), involved in the formation of osteoblasts, lead to the development of OI type V. Up to 5% of patients have OI type V, which is characterized by the formation of a hyperplastic callus after fractures, calcification of the interosseous membrane of the forearm, and a mesh lamellar pattern observed during histological examination of the bone. In 2012, a heterozygous mutation (c.-14C> T) in the 5’-untranslated region (UTR) of the IFITM5 gene was identified as the main cause of OI type V. In the present work, the IFITM5 gene was analyzed and the de novo c.-14C> T mutation was identified in one patient with OI who was subsequently diagnosed with type V of the disease. Three known polymorphic variants were also identified: rs57285449; c.80G> C (p.Gly27Ala) and rs2293745; c.187-45C> T and rs755971385 c.279G> A (p.Thr93 =) and one previously undescribed variant: c.128G> A (p.Ser43Asn) AGC> AAC (S / D), which were not pathogenic. The article focuses on the features of the clinical manifestations of OI type V, and it is recommended to determine the c.-14C> T mutation in the IFITM5 gene if this form of the disease is suspected.

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DIAGNOSTIC VALUE OF SPECIFIC ANTIBODY SYNTHESIS IN BRAIN OF PATIENTS WITH NEUROINFECTIONS

Wiadomości Lekarskie ◽

10.36740/wlek201908103 ◽

2019 ◽

Vol 72 (8) ◽

pp. 1437-1441

Author(s):

Pavel Dyachenko ◽

Igor Filchakov ◽

Anatoly Dyachenko ◽

Victoria Kurhanskaya

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Manifestations ◽

Diagnostic Value ◽

Diagnostic Challenge ◽

Specific Antibodies ◽

Intrathecal Synthesis ◽

Varicella Zoster ◽

Mrz Reaction ◽

Wide Range

Introduction: Viral encephalitis accounts for 40-70% of all cases worldwide, central nervous system infections pose a diagnostic challenge because clinical manifestations are not typically pathognomonic for specific pathogens, and a wide range of agents can be causative. The aim: To assess the diagnostic value of intrathecal synthesis of specific antibodies in patients with inflammatory lesions of the central nervous system. Materials and methods: Within the framework of the study, two groups of 90 people in each were formed from the patients with neuroinfections admitted to our Center. Intrathecal synthesis (ITS) of total (unspecific) IgG in members of one of group (group of compare) was determined. Brain synthesis of specific antibodies (Ab) to some neurotropic pathogens (herpes simplex virus 1/2, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, rubella virus, Borrelies) was studied in the second group of patients (group of interest). There were no statistically significant differences between groups by gender and age. Encephalitis and encephalomyelitis prevailed among patients of both groups Results: ITS of total IgG was established in 30 (33.3 ± 6.1 %) patients of the first group with IgG index more than 0.6 indicating on inflammatory process in CNS and no marked changes of CSF. ITS of specific Ab was determined in 23 of 90 (25.6 ± 4.6 %) patients included into group of interest. In more than half of cases Ab to several infectious agents were detected simultaneously. ITS of various specificity, in particular, to measles and rubella viruses, and VZV, known as MRZ-reaction, is characteristic of some autoimmune lesions of CNS, multiple sclerosis first of all. In fact, further research of 5 patients with MRZ-reaction confirmed their autoimmune failure of CNS. Detection of ITS in the CSF samples didn’t depend on concentration of specific Ab in serum and CSF and wasn’t followed by HEB dysfunctions which were observed with the same frequency in patients with or without ITS (13.0 % and 13.6 % respectively). Conclusion: Specific Ab synthesis to several neurotropic pathogens in the CSF of significant part of examined patients was established. Thus, diagnostic value of ITS of specific immunoglobulins seems to be limited to cases in which autoimmune damage of the CNS is suspected.

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Celiac Disease in Kosovar Albanian Children: Evaluation of Clinical Features and Diagnosis

Current Pediatric Reviews ◽

10.2174/1573396316666200116093753 ◽

2020 ◽

Vol 16 (3) ◽

pp. 241-247

Author(s):

Atifete Ramosaj-Morina ◽

Alije Keka-Sylaj ◽

Arbana Baloku Zejnullahu ◽

Lidvana Spahiu ◽

Virgjina Hasbahta ◽

...

Keyword(s):

Celiac Disease ◽

Disease Onset ◽

Clinical Manifestations ◽

Gastrointestinal Symptoms ◽

Dominant Mode ◽

Primary School Children ◽

Cross Sectional ◽

Classical Form ◽

Wide Range ◽

The Mean

Background: Celiac disease is an immune-mediated disorder characterized by variable clinical manifestations, specific antibodies, HLA-DQ2/DQ8 haplotypes, and enteropathy. Objectives: The aim of this study was to present the clinical spectrum and patterns of celiac disease in Kosovar Albanian children. Methods: A cross-sectional retrospective study was performed with Albanian children aged 0-18 years, treated for celiac disease in the Pediatric Clinic, University Clinical Center of Kosovo from 2005 to 2016. Results: During the study period, 63 children were treated for celiac disease. The mean age at diagnosis was 5.5 years (SD ± 3.31). The mean age at celiac disease onset was 3.3 years (SD ± 2.02), while the mean delay from the first symptoms indicative of celiac disease to diagnosis was 2.2 years (SD ± 2.09). More than 70% of the patients were diagnosed in the first 7 years of life, mainly presented with gastrointestinal symptoms, while primary school children and adolescents mostly showed atypical symptoms (p<0.001). The classical form of celiac disease occurred in 78% of the cases. Sixty (95%) patients carried HLA-DQ2.5, DQ2.2 and/or HLA-DQ8 heterodimers, and only three of them tested negative. Conclusions: Kosovo, as the majority of developing countries, is still facing the classical form of celiac disease as the dominant mode of presentation; as a result, most children with other forms of the celiac disease remain undiagnosed. : Physicians should be aware of the wide range of clinical presentations and utilize low testing thresholds in order to prevent potential long-term problems associated with untreated celiac disease.

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Multiple Myeloma or Brucellosis: A Case Report

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190307123047 ◽

2020 ◽

Vol 20 (1) ◽

pp. 102-105 ◽

Cited By ~ 1

Author(s):

Hossein A. Rahdar ◽

Mansoor Kodori ◽

Mohamad R. Salehi ◽

Mahsa Doomanlou ◽

Morteza Karami-Zarandi ◽

...

Keyword(s):

Multiple Myeloma ◽

Brucella Melitensis ◽

Severe Disease ◽

Correct Diagnosis ◽

Clinical Manifestations ◽

Bone Marrow Aspiration ◽

Major Health Problem ◽

Brucella Infection ◽

Wide Range ◽

Parental Treatment

Background: Brucellosis, a major health problem in developing countries, is a multisystem infection with a broad spectrum of clinical manifestations. Hematological complications, ranging from an intravascular coagulopathy to mild homeostasis disorders (such as gammopathy), have been reported in brucella infection. These signs and symptoms may lead to misdiagnosis of brucellosis with other hematological diseases. Case: A 65-year-old male whose occupation was shepherding was referred to our hospital as a known case of multiple myeloma with continuous fever, muscle weakness, and night sweating after taking 2 courses of chemotherapy. The laboratory diagnosis of multiple myeloma had been based on the observation of a high percent of plasma cells in the bone marrow aspiration. At follow- up, the result of patient's fever workup, with 2 sets of blood cultures, was positive for Brucella melitensis. Isolated brucella was confirmed as B. melitensis by 16S rRNA sequencing. Brucellosis serologic test was performed by agglutination test and positive results were obtained. The patient was discharged with the cessation of fever and general improvement after the end of the parental treatment phase of brucella bacteremia. Conclusions: Brucella infection may cause a severe disease, mimicking a primary hematological disease, which could complicate the correct diagnosis. In brucellosis cases, due to the wide range of symptoms, in addition to cultivation and serological methods, molecular methods should also be used to prevent inappropriate diagnosis and additional costs.

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SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

Science Immunology ◽

10.1126/sciimmunol.abg0833 ◽

2021 ◽

Vol 6 (58) ◽

pp. eabg0833

Author(s):

Bingyu Yan ◽

Tilo Freiwald ◽

Daniel Chauss ◽

Luopin Wang ◽

Erin West ◽

...

Keyword(s):

Epithelial Cells ◽

Clinical Manifestations ◽

Lung Epithelial Cells ◽

Complement Factor ◽

Respiratory Epithelial Cells ◽

Signature Genes ◽

Wide Range ◽

Lung Epithelial ◽

Gene Transcripts ◽

Respiratory Epithelial

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.

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Myocardial amyloidosis following multiple myeloma in a 38-year-old female patient: A case report

Open Medicine ◽

10.1515/med-2020-0125 ◽

2020 ◽

Vol 15 (1) ◽

pp. 396-402

Author(s):

Qisi Zhang ◽

Yingli Qiao ◽

Dongmei Yan ◽

Yuhui Deng ◽

Mengyang Zhang ◽

...

Keyword(s):

Multiple Myeloma ◽

Plasma Cells ◽

Laboratory Data ◽

Young Patients ◽

Clinical Manifestations ◽

The Elderly ◽

First Episode ◽

Rapid Progression ◽

Congo Red Staining ◽

Impaired Cardiac Function

AbstractMultiple myeloma (MM) is an immunoglobulin-producing tumor of plasma cells, which occurs commonly in the elderly. The incidence of myocardial amyloidosis with MM is extremely low and early clinical manifestations are nonspecific. The diversity of clinical manifestations and first episode symptoms often cause misdiagnosis in young patients with myocardial amyloidosis following MM. In this study, we analyzed the clinical data of a young woman with MM and impaired cardiac function combined with echocardiography, electrocardiography (ECG), laboratory data, cell Congo Red staining, and other manifestations to diagnose amyloidosis. Considering the rapid progression, short survival, and poor prognosis in most patients, a clear, definitive, and timely diagnosis is essential for the treatment of patients with MM complicated with myocardial amyloidosis.

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SAT0316 ANTI-PM/SCL ANTIBODIES IN SYSTEMIC SCLEROSIS: CLINICAL ASSOCIATIONS IN THE RESCLE COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3304 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1103.1-1104

Author(s):

N. Iniesta-Arandia ◽

G. Espinosa ◽

A. Guillen del Castillo ◽

C. Tolosa ◽

G. M. Lledó ◽

...

Keyword(s):

Systemic Sclerosis ◽

Survival Data ◽

Death Rate ◽

Administrative Support ◽

Medical Science ◽

Survival Rates ◽

Clinical Manifestations ◽

Study Group ◽

Allergy Immunol ◽

Science Service

Background:Anti-PM/Scl antibodies are associated to systemic sclerosis (SSc) but are not specific to SSc. The true prevalence of anti-PM/Scl antibodies in SSc is unknown, ranging from 2.5% to 12.5%. An association between anti-PM/Scl antibodies with muscular involvement, pulmonary fibrosis, calcinosis, and a relatively benign prognosis have been described.Objectives:To compare the clinical manifestations and prognosis of SSc patients according the presence of anti-PM/Scl antibodies in the cohort of RESCLE (Spanish Scleroderma Registry).Methods:From the Spanish Scleroderma Study Group database, we selected patients in whom anti-PM/Scl antibodies had been tested. We compared demographic features, clinical manifestations, laboratory characteristics, and survival data between patients according the anti-PM/Scl antibodies status.Results:72 out of 947 (7%) patients tested positive for anti-PM/Scl antibodies. As presenting SSc manifestations, patients with anti-PM/Scl antibodies had higher prevalence of puffy fingers (11% versus 2%; p=0.002) and arthralgias (11% versus 4%; p=0.03), and lower prevalence of Raynaud’s phenomenon (65% versus 82%, p=0.002). Regarding cumulative manifestations, myositis (51% versus 15%; p<0.001), arthritis (43% versus 22%; p=0.001), and interstitial lung disease (ILD) (60% versus 45%, p=0.014) were more prevalent in patients with anti-PM/Scl antibodies. In fact, those patients with anti-Pm/Scl antibodies presented with FVC (77.4% ± 23.1% versus 85.8% ± 23,1%; p=0.006) and more severe ILD defined as FVC <70% (41% versus 24%; p=0.004). Death rate was similar in patients with and without PM/Scl antibodies (18% versus 17%; p=0.871).We did not find differences in terms of death rate nor in the causes of death (SSc and non-SSc related) according to the anti-PM/Scl antibodies profile.The 5- and 10-years survival rates of patients with anti-PM/Scl antibodies were 91% and 82% respectively, without differences with those without these antibodies (93% and 85%, respectively).Conclusion:In Spanish SSc patients, the presence of anti-PM/Scl antibodies confer a distinctive clinical profile. However, anti-PM/Scl antibodies do not play a role in the prognosis of these patients.References:[1]Stochmal A, Czuwara J, Trojanowska M, Rudnicka L. Antinuclear antibodies in systemic sclerosis: an update. Clin Rev Allergy Immunol 2020;58(1):40-51. doi: 10.1007/s12016-018-8718-8.Acknowledgments:We gratefully acknowledge all investigators who are part of the RESCLE Registry. We also thank the RESCLE Registry Coordinating Centre, S&H Medical Science Service, for their quality control data, logistic and administrative support and Prof. Salvador Ortiz, Universidad Autónoma de Madrid and Statistical Advisor S&H Medical Science Service for the statistical analysis of the data presented in this paper.Disclosure of InterestsNerea Iniesta-Arandia: None declared, Gerard Espinosa Speakers bureau: Glaxo-Smith-Kline, Janssen, Boehringer, Rovi, Alfredo Guillen del Castillo: None declared, Carles Tolosa Consultant of: Actelion pharmaceuticals, GSK, MSD., Gema Maria Lledó: None declared, Dolores Colunga Argüelles Consultant of: Actelion pharmaceuticals, GSK, MSD., Cristina González-Echávarri: None declared, Luis Sáez-Comet: None declared, Norberto Ortego: None declared, Jose Antonio Vargas-Hitos: None declared, Manuel Rubio-Rivas: None declared, Mayka Freire: None declared, Juan José Rios: None declared, Monica Rodriguez-Carballeira: None declared, Luis Trapiella Martínez: None declared, Vicent Fonollosa Pla Speakers bureau: Actelion, Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD., on behalf of RESCLE Investigators, Autoimmune Diseases Study Group (GEAS): None declared

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