scholarly journals LMD-22. Clinicopathological spectrum of leptomeningeal metastases: A 3 year retrospective study

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii12-iii12
Author(s):  
Saloni Pahwa ◽  
Anila Sharma ◽  
Meenakshi Kamboj ◽  
Anurag Mehta
Keyword(s):  
Inflammatory Diseases ◽  
Simple Procedure ◽  
Primary Tumour ◽  
Leptomeningeal Metastases ◽  
Therapeutic Interventions ◽  
Malignant Cells ◽  
Csf Cytology ◽  
Cytological Examination ◽  
Solid Malignancies ◽  
Clinical Records

Abstract Objectives Cytological examination of cerebrospinal fluid is a widely used cost effective, simple procedure and a reliable routine diagnostic test. CSF cytology helps in detection of inflammatory diseases of the CNS, diagnosis of subarachnoid haemorrhage and the identification of malignant cells in metastatic or rarely primary CNS malignancies.Leptomeningeal metastases (LM) is estimated to occur in 5% of all patients with cancer. It has a higher propensity to occur in solid tumours compared to haematological malignancies.In view of poor prognosis, early diagnosis may aid in appropriate tumour staging and aggressive therapeutic intervention. Methods All the samples of CSF received in the Department of Laboratory for cytological examination and reported as ‘positive for malignant cells’ during the year January 2018 to December 2020were included in the study. All the cases were routinely evaluated on Neubauer’s chamber, direct smear and a cytospin preparation stained using MGG stain. The clinical records and any further ancillary testing performed were retrospectively analysed. Results 87cases with LM were identified over 3 year duration. Mean age of presentation was 43 years. Metastatic solid malignancies (56%) had a higher incidence of leptomeningeal metastases compared to haematolymphoid malignancies (40%) and CNS medulloblastomas(2%). Most common solid tumour with involvement of CSF was adenocarcinoma lung (51%) followed by breast carcinoma (37%). Of all the cases of adenocarcinoma lung with LM, EGFR mutant NSCLC were 40% while 8% showed ALK gene rearrangement. Amongst the haematological malignancies, acute leukaemia’s constituted 67% of cases while systemic NHLs were 34%. Most of the cases (97%) presented with neurological symptoms during the course of treatment while 3 cases (3%) showed LM at the time of first presentation. Conclusions With appropriate clinicoradiological correlation, CSF cytology remains the gold standard for identification of malignant cells in cases with already known primary tumour (leptomeningeal dissemination of the disease). In this study, clinical features of both solid and haematolymphoid malignancies were evaluated. The group of solid malignancies included adenocarcinomas lung, breast, gastrointestinal tract and renal cell carcinoma. With the availability of EGFR TKIs and ALK inhibitors, overall survival of the patients may be prolonged with therapeutic interventions despite limited CSF and CNS penetration of these drugs.

Diagnostic spectrum of CSF involvement by malignant cells: three-year experience of tertiary care hospital in CSF cytology

2017 ◽  
Vol 5 (6) ◽  
pp. 2575
Author(s):  
Vandana Rana ◽  
Avnit Sidhu ◽  
Rajat Jagani ◽  
Giriraj Singh ◽  
Rajeshwar Singh ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Standard Test ◽  
Care Hospital ◽  
Malignant Cells ◽  
Csf Cytology ◽  
Positive Cytology ◽  
Solid Malignancies ◽  
Special Stain ◽  
Primary Origin ◽  
Metastatic Involvement

Background: Cerebrospinal fluid (CSF) cytology is the diagnostic gold standard test for primary or metastatic involvement of central nervous system (CNS) by malignancy. It is a very important and routinely done test in the laboratory but its sensitivity is low due to many confounding factors and varies amongst type of malignancies. We did retrospective analysis of CSF cytology carried out at our center from January 2013 to December 2015 to find out about spectrum of malignancies being detected on CSF cytology.Methods: From January 2013 to December 2015, three hundred and seventy-five CSF samples were received and processed for presence of malignant cells at our center. The cytospin preparations stained with LG and PAP stains of these CSF samples were analyzed along with any special stain that was available in the records. Clinical details of the patients with positive cytology were correlated from records.Results: The diagnostic spectrum obtained through study of positive CSF cytology included cases of metastatic solid malignancies and hematolymphoid malignancies. Four cases out of ten were of Metastatic Adenocarcinoma with primary origin being Breast, Lung and Stomach. Out of six cases of hematolymphoid malignancies; five were known cases of lymphoma/leukemia and one was primarily diagnosed to have Non-Hodgkin’s lymphoma (NHL) on CSF cytology.Conclusions: Both Epithelial and Hematolymphoid malignancies can be diagnosed on CSF cytology and these are predominantly metastatic in origin; Hematolymphoid malignancies are more common in CSF than solid malignancies. Correlation with clinical details and Neuroimaging is a must.

scholarly journals Haemostatic abnormalities in solid malignancies

2018 ◽  
Vol 7 (1) ◽  
pp. 141
Author(s):  
Supriya D. Joshi ◽  
Hemant G. Murdeshwar ◽  
Gopal A. Pandit
Keyword(s):  
Platelet Count ◽  
Advanced Disease ◽  
Tertiary Care ◽  
Therapeutic Interventions ◽  
Tertiary Care Centre ◽  
Cytological Examination ◽  
Solid Malignancies ◽  
Advanced Stages ◽  
A Prospective Study ◽  
D Dimer

Background: Though the actual symptoms of any haemostatic abnormalities in patients of solid malignancies are not seen commonly screening in all such cases can guide us to correct those abnormalities in time and improve the outcome. The present study is undertaken with an objective to find out coagulation disorders in patients of solid malignancies and compare their levels according to the stage of the cancer.Methods: A prospective study was undertaken in a tertiary care centre in Maharashtra, India from December 2010 to September 2012. Total 102 cases with malignancies diagnosed on histopathology/cytological examination were tested for BT, CT, Platelet count, PT, APTT, TT and D-dimer levels. These tests were repeated on first postoperative or post chemotherapy day wherever possible. Early and advanced stages of cancer were divided according to the spread of the tumor. Results were compared between the two. DIC cases were also noted.Results: Out of 102 cases studied, haemostatic abnormalities were more common in adenocarcinomas that too in mucin secreting adenocarcinomas. The percentage of cases with increased D-dimer values was higher in the advanced disease compared to early disease. The PT, APTT, TT and platelet count showed statistically significant differences between the early and advanced disease groups. Compared to preoperative values, postoperative values were abnormal but the change was not statistically significant.Conclusions: Screening for coagulation profile in all solid malignancies can help to predict the chances of complication and therapeutic interventions can be done.

Nuclear receptor Nur77: its role in chronic inflammatory diseases

2021 ◽  
Author(s):  
Sanne C. Lith ◽  
Carlie J.M. de Vries
Keyword(s):  
Nuclear Receptor ◽  
Inflammatory Disease ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Experimental Models ◽  
Therapeutic Interventions ◽  
Alternative Mechanism ◽  
Signaling Complex

Abstract Nur77 is a nuclear receptor that has been implicated as a regulator of inflammatory disease. The expression of Nur77 increases upon stimulation of immune cells and is differentially expressed in chronically inflamed organs in human and experimental models. Furthermore, in a variety of animal models dedicated to study inflammatory diseases, changes in Nur77 expression alter disease outcome. The available studies comprise a wealth of information on the function of Nur77 in diverse cell types and tissues. Negative cross-talk of Nur77 with the NFκB signaling complex is an example of Nur77 effector function. An alternative mechanism of action has been established, involving Nur77-mediated modulation of metabolism in macrophages as well as in T cells. In this review, we summarize our current knowledge on the role of Nur77 in atherosclerosis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and sepsis. Detailed insight in the control of inflammatory responses will be essential in order to advance Nur77-targeted therapeutic interventions in inflammatory disease.

scholarly journals Malignant cells in cerebrospinal fluid (CSF): The meaning of a positive CSF cytology

Neurology ◽  
2011 ◽  
Vol 77 (20) ◽  
pp. 1793-1793
Author(s):  
J. P. Glass ◽  
M. Melamed ◽  
N. L. Chernik ◽  
J. B. Posner
Keyword(s):  
Cerebrospinal Fluid ◽  
Malignant Cells ◽  
Csf Cytology

scholarly journals Weakly supervised learning for classification of lung cytological images using attention-based multiple instance learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Atsushi Teramoto ◽  
Yuka Kiriyama ◽  
Tetsuya Tsukamoto ◽  
Eiko Sakurai ◽  
Ayano Michiba ◽  
...  
Keyword(s):  
Supervised Learning ◽  
Classification Performance ◽  
Multiple Instance Learning ◽  
Cancer Type ◽  
Malignant Cells ◽  
Cytological Examination ◽  
Automated Method ◽  
Weakly Supervised ◽  
Better Than

AbstractIn cytological examination, suspicious cells are evaluated regarding malignancy and cancer type. To assist this, we previously proposed an automated method based on supervised learning that classifies cells in lung cytological images as benign or malignant. However, it is often difficult to label all cells. In this study, we developed a weakly supervised method for the classification of benign and malignant lung cells in cytological images using attention-based deep multiple instance learning (AD MIL). Images of lung cytological specimens were divided into small patch images and stored in bags. Each bag was then labeled as benign or malignant, and classification was conducted using AD MIL. The distribution of attention weights was also calculated as a color map to confirm the presence of malignant cells in the image. AD MIL using the AlexNet-like convolutional neural network model showed the best classification performance, with an accuracy of 0.916, which was better than that of supervised learning. In addition, an attention map of the entire image based on the attention weight allowed AD MIL to focus on most malignant cells. Our weakly supervised method automatically classifies cytological images with acceptable accuracy based on supervised learning without complex annotations.

scholarly journals COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid

2020 ◽  
Author(s):  
Sarah Heili-Frades ◽  
Pablo Minguez ◽  
Ignacio Mahillo Fernández ◽  
Tomás Prieto-Rumeau ◽  
Antonio Herrero González ◽  
...  
Keyword(s):  
Multivariate Logistic Regression Analysis ◽  
Heart Rhythm ◽  
Population Based ◽  
Public Hospitals ◽  
Therapeutic Interventions ◽  
Limited Information ◽  
Elevated Systolic Blood Pressure ◽  
Mortality Incidence ◽  
Universal Relationship ◽  
Clinical Records

ABSTRACTThere is limited information describing features and outcomes of patients requiring hospitalization for COVID19 disease and still no treatments have clearly demonstrated efficacy. Demographics and clinical variables on admission, as well as laboratory markers and therapeutic interventions were extracted from electronic Clinical Records (eCR) in 4712 SARS-CoV2 infected patients attending 4 public Hospitals in Madrid. Patients were stratified according to age and stage of severity. Using multivariate logistic regression analysis, cut-off points that best discriminated mortality were obtained for each of the studied variables. Principal components analysis and a neural network (NN) algorithm were applied.A high mortality incidence associated to age >70, comorbidities (hypertension, neurological disorders and diabetes), altered vitals such as fever, heart rhythm disturbances or elevated systolic blood pressure, and alterations in several laboratory tests. Remarkably, analysis of therapeutic options either taken individually or in combination drew a universal relationship between the use of Cyclosporine A and better outcomes as also a benefit of tocilizumab and/or corticosteroids in critically ill patients.We present a large Spanish population-based study addressing factors influencing survival in current SARS CoV2 pandemic, with particular emphasis on the effectivity of treatments. In addition, we have generated an NN capable of identifying severity predictors of SARS CoV2. A rapid extraction and management of data protocol from eCR and artificial intelligence in-house implementations allowed us to perform almost real time monitoring of the outbreak evolution.

scholarly journals SARS-CoV-2 infection induces inflammatory bone loss in golden Syrian hamsters

2021 ◽  
Author(s):  
Kelvin Yeung ◽  
Wei Qiao ◽  
Hui En Lau ◽  
Hui Zhi Xie ◽  
Vincent Poon ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Inflammatory Diseases ◽  
Lumbar Vertebrae ◽  
Recovery Phase ◽  
Therapeutic Interventions ◽  
Limited Information ◽  
Hamster Model ◽  
Golden Syrian Hamster ◽  
Organ Systems

Abstract Extrapulmonary complications of different organ systems have been increasingly recognized in patients with severe or chronic Coronavirus Disease 2019 (COVID-19). However, limited information on the skeletal complications of COVID-19 is known, even though inflammatory diseases of the respiratory tract have been known to perturb bone metabolism and cause pathological bone loss. In this study, we characterized the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on bone metabolism in an established golden Syrian hamster model for COVID-19. SARS-CoV-2 causes significant multifocal loss of bone trabeculae in the long bones and lumbar vertebrae of all infected hamsters. The bone loss progressively worsens from the acute phase to the post-recovery phase. Mechanistically, the bone loss was associated with SARS-CoV-2-induced cytokine dysregulation which upregulates osteoclastic differentiation of monocyte-macrophage lineage. The pro-inflammatory cytokines further trigger a second wave of cytokine storm in the skeletal tissues to augment their pro-osteoclastogenesis effect. Our findings in this established hamster model suggest that pathological bone loss may be a neglected complication which warrants more extensive investigations during the long-term follow-up of COVID-19 patients. The benefits of potential prophylactic and therapeutic interventions against pathological bone loss should be further evaluated.

scholarly journals Folate Receptor β (FRβ) Expression in Tissue-Resident and Tumor-Associated Macrophages Associates with and Depends on the Expression of PU.1

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1445
Author(s):  
Rafael Samaniego ◽  
Ángeles Domínguez-Soto ◽  
Manohar Ratnam ◽  
Takami Matsuyama ◽  
Paloma Sánchez-Mateos ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Folate Receptor ◽  
Regulatory Region ◽  
Therapeutic Interventions ◽  
Gene Profile ◽  
Tumor Associated Macrophages ◽  
Human Macrophages ◽  
Pathological Conditions ◽  
Functional Relevance ◽  
Macrophage Subset

As macrophages exhibit a huge functional plasticity under homeostasis and pathological conditions, they have become a therapeutic target for chronic inflammatory diseases. Hence, the identification of macrophage subset-specific markers is a requisite for the development of macrophage-directed therapeutic interventions. In this regard, the macrophage-specific Folate Receptor β (FRβ, encoded by the FOLR2 gene) has been already validated as a target for molecular delivery in cancer as well as in macrophage-targeting therapeutic strategies for chronic inflammatory pathologies. We now show that the transcriptome of human macrophages from healthy and inflamed tissues (tumor; rheumatoid arthritis, RA) share a significant over-representation of the “anti-inflammatory gene set”, which defines the gene profile of M-CSF-dependent IL-10-producing human macrophages (M-MØ). More specifically, FOLR2 expression has been found to strongly correlate with the expression of M-MØ-specific genes in tissue-resident macrophages, tumor-associated macrophages (TAM) and macrophages from inflamed synovium, and also correlates with the presence of the PU.1 transcription factor. In fact, PU.1-binding elements are found upstream of the first exon of FOLR2 and most M-MØ-specific- and TAM-specific genes. The functional relevance of PU.1 binding was demonstrated through analysis of the proximal regulatory region of the FOLR2 gene, whose activity was dependent on a cluster of PU.1-binding sequences. Further, siRNA-mediated knockdown established the importance of PU.1 for FOLR2 gene expression in myeloid cells. Therefore, we provide evidence that FRβ marks tissue-resident macrophages as well as macrophages within inflamed tissues, and its expression is dependent on PU.1.

Role of inflammasomes in pathogenesis of diseases with a high impact on public health

2018 ◽  
pp. 77-89
Author(s):  
С.В. Пирожков ◽  
П.Ф. Литвицкий
Keyword(s):  
Public Health ◽  
Inflammatory Diseases ◽  
Animal Experiments ◽  
High Impact ◽  
Therapeutic Interventions ◽  
Mouse Strains ◽  
Pathogenic Microorganisms ◽  
Inflammatory Damage ◽  
Decay Products

Инфламмасома - важный компонент нативного иммунитета. Она представляет собой макромолекулярный комплекс, включающий сенсорные элементы, адапторные белки и зимоген каспазы-1. Под действием продуктов распада тканей и патогенных микроорганизмов инфламмасома активируется и превращает про-IL-1b и про-IL-18 в активные интерлейкины. Активация инфламмасом отмечена при многих воспалительных заболеваниях и служит мишенью для терапевтических воздействий. В настоящем обзоре обсуждается вклад инфламмасом в патогенез социально-значимых заболеваний человека, таких, как атеросклероз, ишемическая болезнь сердца, сахарный диабет, артриты, болезни легких, печени и почек. Результаты клинических исследований и модельных экспериментов на линиях мышей с нокаутированными генами компонентов инфламмасомы говорят о существенной роли этих структур в прогрессировании патологии, связанной с воспалительным повреждением тканей. An inflammasome becomes activated under the action of tissue decay products or pathogenic microorganisms and converts pro-IL-1 and pro-IL-18 to their active forms. Activation of inflammasomes has been reported in many inflammatory diseases and serves as a target for therapeutic interventions. The present review discusses the contribution of inflammasomes to pathogenesis of diseases with a high impact on public health, such as atherosclerosis, ischemic heart disease, diabetes mellitus, arthritis, diseases of lungs and kidneys. Results of clinical studies and animal experiments on knockout mouse strains with a deficit of inflammasome components suggest a significant role of these structures in progression of pathology associated with inflammatory damage to tissues.

Obesity, asthma, and oxidative stress

2010 ◽  
Vol 108 (3) ◽  
pp. 754-759 ◽  
Author(s):  
Fernando Holguin ◽  
Anne Fitzpatrick
Keyword(s):  
Oxidative Stress ◽  
Inhaled Corticosteroids ◽  
Inflammatory Diseases ◽  
Therapeutic Interventions ◽  
Antioxidant Defenses ◽  
Oxidative Stress Biomarkers ◽  
Public Health Policies ◽  
Asthma Patients ◽  
Nonalcoholic Hepatic Steatosis ◽  
And Oxidative Stress

Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance, comorbidities, and reduced antioxidant defenses. While obesity-mediated increased oxidative stress plays an important role in the pathogenesis of vascular disease and nonalcoholic hepatic steatosis, little is known of how it may affect the lung. Contrary to what has previously been thought, the combination of obesity and asthma, both chronic inflammatory diseases, does not necessarily result in a synergistic effect, leading to even greater oxidative stress. However, most available studies have compared the levels of oxidative stress biomarkers on stable asthma patients, and it is possible that the interaction of oxidative stress between obesity and asthma is not readily detectable under basal conditions. We propose that obesity-mediated oxidative stress, which may affect the lung function of asthmatic subjects by increasing airway inflammation and reducing the effectiveness of inhaled corticosteroids, may become evident during exposure to an aggravating factor or during periods of asthma exacerbation. Understanding whether obesity-mediated oxidative stress has a mechanistic role in the association between obesity and asthma will help in the formation of public health policies and increase our capacity to develop therapeutic interventions that improve the life of obese asthmatic subjects.

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