Following the discovery of anti-MDA5 Ab, the clinical understanding of dermatomyositis has been improved

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Large Scale ◽  
Early Stage ◽  
Total Mortality ◽  
Epidemiological Studies ◽  
Respiratory Physiology ◽  
Prognostic Indicators ◽  
Current Standard ◽  
Incurable Disease ◽  
Triple Treatment ◽  
Risk Categorization

Knowledge about clinically amyopathic dermatomyositis has exploded in the last two decades, especially after the discovery of anti-MDA5 Ab. The disease's likely genesis and pathophysiological processes have been studied in a number of scientific and epidemiological studies. Thanks to a slew of new large-scale cohort studies, the clinical characteristics of MDA5+ DM may be better identified. In addition, several prognostic indicators have been discovered, such as respiratory physiology measures and serum biomarkers, which have helped to enhance risk categorization in clinical practice and restrict the design of future clinical studies. Quantitative evaluation of pulmonary HRCT data may be the trend of imaging testing in MDA5+ DM-ILD. The current standard of treatment for MDA5+ DM-ILD is "triple treatment" with JAK inhibitors, which has been proven in recent trials to significantly improve the survival of early-stage patients. Total mortality in this incurable disease, however, is still shockingly high, especially in advanced-stage patients. There is still a pressing need for a more effective and well-evidenced treatment approach for MDA5+ DM-ILD.

A CLINICAL CASE OF PRIMARY HYPERPARATHYROIDISM OF THE OSTEO-VISCERAL FORM

2020 ◽  
pp. 155-161
Author(s):  
Poselyugina O.B. ◽  
Kulish A.S. ◽  
Vasiliev D.F.
Keyword(s):  
Primary Hyperparathyroidism ◽  
Clinical Case ◽  
Early Stage ◽  
Diagnostic Errors ◽  
Epidemiological Studies ◽  
Medical Documentation ◽  
Screening Methods ◽  
Internal Organs ◽  
Blood Calcium ◽  
Slow Development

Introduction. Primary hyperparathyroidism is an endocrine disease resulting from a primary pathology of the parathyroid gland, characterized by increased secretion of parathyroid hormone and increased blood calcium levels. Among the endocrine diseases, primary hyperparathyroidism is the third most common after diabetes mellitus and thyroid disease. In Russia, according to epidemiological studies, primary hyperparathyroidism is found in 1% of the population, women suffer 2-3 times more often than men do, and the average age of diagnosis is 54-59 years. In the absence of a timely diagnosis, primary hyperparathyroidism causes systemic damage to internal organs: renal impairment, nephrolithiasis, esophageal affection, cardiovascular and nervous system involvement, and it leads to a violation of bone tissue integrity. The aim is to demonstrate a clinical case of a patient with primary hyperparathyroidism and to analyze the stages of diagnosis of the disease and treatment. Material and methods. The review of medical literature on the problem of diagnostics and treatment of primary hyperparathyroidism was performed, as well as an analysis of the patient’s medical documentation with this pathology. Results and discussion. A variant of complicated course of primary hyperparathyroidism of bone and visceral form is considered. About 15 years passed from the moment of appearance of the first symptoms of the disease to the development of complications of renal and bone system. Despite the slow development of the disease and availability of screening methods, hyperparathyroidism was detected at the stage of complications. This article provides a detailed analysis of the primary hyperparathyroidism history, as well as analyzes the possibilities of diagnosis, treatment and prevention of this pathology. The efficacy of the therapy has been assessed, and ways of correction have been outlined. The analysis of the reasons that made it difficult to diagnose this pathology at an early stage, before the development of serious complications of internal organs, has been carried out. Conclusions: It can be assumed that the presented clinical case will increase the awareness of physicians, especially therapists, about the primary manifestations of this pathology and the peculiarities of its detection and routing the patient, which will allow avoiding many diagnostic errors.

Konkurrenz zwischen Stieleiche und Buche auf Lothar-Sturmflächen | Competition between pedunculate oak and European beech on Lothar windthrow areas

2009 ◽  
Vol 160 (5) ◽  
pp. 114-123 ◽  
Author(s):  
Daniel Otto ◽  
Sven Wagner ◽  
Peter Brang
Keyword(s):  
Large Scale ◽  
Early Stage ◽  
Tree Height ◽  
European Beech ◽  
Threshold Value ◽  
Test Methods ◽  
Permanent Plots ◽  
Pedunculate Oak ◽  
Competitive Pressure ◽  
Competition Index

The competitive pressure of naturally regenerated European beech (Fagus sylvatica) saplings on planted pedunculate oak (Quercus robur) was investigated on two 1.8 ha permanent plots near Habsburg and Murten (Switzerland). The plots were established with the aim to test methods of artificial oak regeneration after large-scale windthrow. On both plots, 80 oaks exposed to varying levels of competitive pressure from at most 10 neighbouring beech trees were selected. The height of each oak as well as stem and branch diameters were measured. The competitive pressure was assessed using Schütz's competition index, which is based on relative tree height, crown overlap and distance from competing neighbours. Oak trees growing without or with only slight competition from beech were equally tall, while oaks exposed to moderate to strong competition were smaller. A threshold value for the competition index was found above which oak height decreased strongly. The stem and branch diameters of the oaks started to decrease even if the competition from beech was slight, and decreased much further with more competition. The oak stems started to become more slender even with only slight competition from beech. On the moderately acid beech sites studied here, beech grow taller faster than oak. Thus where beech is competing with oak and the aim is to maintain the oak, competitive pressure on the oak must be reduced at an early stage. The degree of the intervention should, however, take the individual competitive interaction into account, with more intervention if the competition is strong.

scholarly journals Non-Albumin Proteinuria (NAP) as a Complementary Marker for Diabetic Kidney Disease (DKD)

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 224
Author(s):  
Jaehyun Bae ◽  
Young Jun Won ◽  
Byung-Wan Lee
Keyword(s):  
Kidney Disease ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Estimated Glomerular Filtration Rate ◽  
Early Stage ◽  
Screening Tools ◽  
Tubular Injury ◽  
Current Standard ◽  
Diabetic Kidney ◽  
Wide Range

Diabetic kidney disease (DKD) is one of the most common forms of chronic kidney disease. Its pathogenic mechanism is complex, and it can affect entire structures of the kidney. However, conventional approaches to early stage DKD have focused on changes to the glomerulus. Current standard screening tools for DKD, albuminuria, and estimated glomerular filtration rate are insufficient to reflect early tubular injury. Therefore, many tubular biomarkers have been suggested. Non-albumin proteinuria (NAP) contains a wide range of tubular biomarkers and is convenient to measure. We reviewed the clinical meanings of NAP and its significance as a marker for early stage DKD.

scholarly journals Lack of an association between gallstone disease and bilirubin levels with risk of colorectal cancer: a Mendelian randomisation analysis

2021 ◽  
Author(s):  
Richard Culliford ◽  
Alex J. Cornish ◽  
Philip J. Law ◽  
Susan M. Farrington ◽  
Kimmo Palin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Large Scale ◽  
Causal Effect ◽  
Gallstone Disease ◽  
Epidemiological Studies ◽  
Mendelian Randomisation ◽  
Linear Relationships ◽  
Potential Risk Factors ◽  
The Relationship ◽  
Circulating Levels

Abstract Background Epidemiological studies of the relationship between gallstone disease and circulating levels of bilirubin with risk of developing colorectal cancer (CRC) have been inconsistent. To address possible confounding and reverse causation, we examine the relationship between these potential risk factors and CRC using Mendelian randomisation (MR). Methods We used two-sample MR to examine the relationship between genetic liability to gallstone disease and circulating levels of bilirubin with CRC in 26,397 patients and 41,481 controls. We calculated the odds ratio per genetically predicted SD unit increase in log bilirubin levels (ORSD) for CRC and tested for a non-zero causal effect of gallstones on CRC. Sensitivity analysis was applied to identify violations of estimator assumptions. Results No association between either gallstone disease (P value = 0.60) or circulating levels of bilirubin (ORSD = 1.00, 95% confidence interval (CI) = 0.96–1.03, P value = 0.90) with CRC was shown. Conclusions Despite the large scale of this study, we found no evidence for a causal relationship between either circulating levels of bilirubin or gallstone disease with risk of developing CRC. While the magnitude of effect suggested by some observational studies can confidently be excluded, we cannot exclude the possibility of smaller effect sizes and non-linear relationships.

scholarly journals Multimorbidity clusters in patients with chronic obstructive airway diseases in the EpiChron Cohort

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jonás Carmona-Pírez ◽  
Beatriz Poblador-Plou ◽  
Ignatios Ioakeim-Skoufa ◽  
Francisca González-Rubio ◽  
Luis Andrés Gimeno-Feliú ◽  
...  
Keyword(s):  
Substance Use ◽  
Chronic Conditions ◽  
Large Scale ◽  
Mental Health Problems ◽  
Epidemiological Studies ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Airway Diseases ◽  
Obstructive Sleep ◽  
Obstructive Airway Diseases

AbstractChronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis, and obstructive sleep apnea (OSA) are amongst the most common treatable and preventable chronic conditions with high morbidity burden and mortality risk. We aimed to explore the existence of multimorbidity clusters in patients with such diseases and to estimate their prevalence and impact on mortality. We conducted an observational retrospective study in the EpiChron Cohort (Aragon, Spain), selecting all patients with a diagnosis of allergic rhinitis, asthma, COPD, and/or OSA. The study population was stratified by age (i.e., 15–44, 45–64, and ≥ 65 years) and gender. We performed cluster analysis, including all chronic conditions recorded in primary care electronic health records and hospital discharge reports. More than 75% of the patients had multimorbidity (co-existence of two or more chronic conditions). We identified associations of dermatologic diseases with musculoskeletal disorders and anxiety, cardiometabolic diseases with mental health problems, and substance use disorders with neurologic diseases and neoplasms, amongst others. The number and complexity of the multimorbidity clusters increased with age in both genders. The cluster with the highest likelihood of mortality was identified in men aged 45 to 64 years and included associations between substance use disorder, neurologic conditions, and cancer. Large-scale epidemiological studies like ours could be useful when planning healthcare interventions targeting patients with chronic obstructive airway diseases and multimorbidity.

scholarly journals De-Escalation of Therapy for Patients with Early-Stage Squamous Cell Carcinoma of the Anus

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2099
Author(s):  
Eric Miller ◽  
Jose Bazan
Keyword(s):  
Squamous Cell Carcinoma ◽  
Radiation Therapy ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Intensity Modulated Radiation Therapy ◽  
Late Toxicity ◽  
Standard Of Care ◽  
The Elderly ◽  
Current Standard

The incidence of squamous cell carcinoma of the anus (SCCA) is increasing, particularly in the elderly, with increased mortality in this age group. While the current standard of care for localized SCCA remains chemoradiation (CRT), completion of this treatment can be challenging with risks for severe acute and late toxicity. It remains unclear if full course CRT is required for the management of early-stage SCCA or if de-escalation of treatment is possible without compromising patient outcomes. Alternative therapies include radiation therapy alone or local excision for appropriate patients. Modifying standard CRT may also reduce toxicity including the routine use of intensity-modulated radiation therapy for treatment delivery, modification of treatment volumes, and selection and dosing of concurrent systemic therapy agents. Finally, we provide an overview of currently accruing prospective trials focused on defining the role of de-escalation of therapy in patients with early-stage SCCA.

scholarly journals Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

2021 ◽  
Vol 22 (15) ◽  
pp. 7917
Author(s):  
Hideaki Kaneto ◽  
Tomohiko Kimura ◽  
Masashi Shimoda ◽  
Atsushi Obata ◽  
Junpei Sanada ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Function ◽  
Apoptotic Cell ◽  
Early Stage ◽  
Insulin Biosynthesis ◽  
Protective Effects ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Glucose Toxicity

Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

scholarly journals Multicenter Evaluation of an ELISA for the Detection of Cryptosporidium spp. Antigen in Clinical Human Stool Samples

2021 ◽  
Vol 9 (2) ◽  
pp. 209
Author(s):  
Romy Razakandrainibe ◽  
Célia Mérat ◽  
Nathalie Kapel ◽  
Marc Sautour ◽  
Karine Guyot ◽  
...  
Keyword(s):  
Large Scale ◽  
Cryptosporidium Oocyst ◽  
Clinical Importance ◽  
Epidemiological Studies ◽  
Elisa Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cryptosporidium Spp ◽  
Stool Samples ◽  
Conventional Microscopy ◽  
Human Stool

Human cryptosporidiosis remains underdiagnosed, and rapid/accurate diagnosis is of clinical importance. Diagnosis of the Cryptosporidium oocyst in stool samples by conventional microscopy is labor-intensive, time-consuming, and requires skillful experience. Thus, we aimed to evaluate the usefulness of a coproantigen enzyme-linked immunosorbent assay (ELISA) test in detecting Cryptosporidium spp. from fecal specimens. For this aim, we evaluated the performances of a commercial ELISA (CoproELISA Cryptosporidium kit, Savyon Diagnostics, Israel) for the detection of Cryptosporidium spp. in random clinical stool samples through a multicenter study. The sensitivity and specificity for coproantigen ELISA were 98.86% and 94.32%, respectively. The coproantigen ELISA results indicate that the simple, rapid, reliable, and standardized immunoassay test is sensitive and specific for routine diagnosis, and may be useful for large-scale epidemiological studies of cryptosporidiosis.

scholarly journals Understanding the Processes Causing the Early Intensification of Hurricane Dorian through an Ensemble of the Hurricane Analysis and Forecast System (HAFS)

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 93
Author(s):  
Andrew Hazelton ◽  
Ghassan J. Alaka ◽  
Levi Cowan ◽  
Michael Fischer ◽  
Sundararaman Gopalakrishnan
Keyword(s):  
Tropical Cyclone ◽  
Large Scale ◽  
Early Stage ◽  
Early Period ◽  
Storm Track ◽  
Key Factors ◽  
Complex Interplay ◽  
Forecast System ◽  
Model Initialization

The early stages of a tropical cyclone can be a challenge to forecast, as a storm consolidates and begins to grow based on the local and environmental conditions. A high-resolution ensemble of the Hurricane Analysis and Forecast System (HAFS) is used to study the early intensification of Hurricane Dorian, a catastrophic 2019 storm in which the early period proved challenging for forecasters. There was a clear connection in the ensemble between early storm track and intensity: stronger members moved more northeast initially, although this result did not have much impact on the long-term track. The ensemble results show several key factors determining the early evolution of Dorian. Large-scale divergence northeast of the tropical cyclone (TC) appeared to favor intensification, and this structure was present at model initialization. There was also greater moisture northeast of the TC for stronger members at initialization, favoring more intensification and downshear development of the circulation as these members evolved. This study highlights the complex interplay between synoptic and storm scale processes in the development and intensification of early-stage tropical cyclones.

scholarly journals Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening

2019 ◽  
Vol 25 (1) ◽  
pp. 9-20 ◽  
Author(s):  
Olivia W. Lee ◽  
Shelley Austin ◽  
Madison Gamma ◽  
Dorian M. Cheff ◽  
Tobie D. Lee ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
High Throughput ◽  
High Throughput Screening ◽  
Drug Targets ◽  
Large Scale ◽  
Early Stage ◽  
Cancer Cell Line ◽  
Hek 293 ◽  
Cytotoxic Compounds

Cell-based phenotypic screening is a commonly used approach to discover biological pathways, novel drug targets, chemical probes, and high-quality hit-to-lead molecules. Many hits identified from high-throughput screening campaigns are ruled out through a series of follow-up potency, selectivity/specificity, and cytotoxicity assays. Prioritization of molecules with little or no cytotoxicity for downstream evaluation can influence the future direction of projects, so cytotoxicity profiling of screening libraries at an early stage is essential for increasing the likelihood of candidate success. In this study, we assessed the cell-based cytotoxicity of nearly 10,000 compounds in the National Institutes of Health, National Center for Advancing Translational Sciences annotated libraries and more than 100,000 compounds in a diversity library against four normal cell lines (HEK 293, NIH 3T3, CRL-7250, and HaCat) and one cancer cell line (KB 3-1, a HeLa subline). This large-scale library profiling was analyzed for overall screening outcomes, hit rates, pan-activity, and selectivity. For the annotated library, we also examined the primary targets and mechanistic pathways regularly associated with cell death. To our knowledge, this is the first study to use high-throughput screening to profile a large screening collection (>100,000 compounds) for cytotoxicity in both normal and cancer cell lines. The results generated here constitute a valuable resource for the scientific community and provide insight into the extent of cytotoxic compounds in screening libraries, allowing for the identification and avoidance of compounds with cytotoxicity during high-throughput screening campaigns.

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