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Hepatic Medicine : Evidence and Research 2019Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as... (Review)
Review
Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options - past, present, and future, in patients with severe alcoholic hepatitis.
PubMed: 31496843
DOI: 10.2147/HMER.S197933 -
Revue Medicale de Liege May 2018Cardiac arrhythmias are a common cause of admission in the emergency department. Among these, atrio-ventricular conductive disorders and malignant ventricular... (Review)
Review
Cardiac arrhythmias are a common cause of admission in the emergency department. Among these, atrio-ventricular conductive disorders and malignant ventricular arrhythmias are among the most severe, requiring prompt and appropriate management to ensure the best prognosis. Knowledge of the pathophysiology and etiology causing these arrhythmias is mandatory in order to understand its management, acute and chronic, and to facilitate the dialogue between emergency physicians and cardiologists.
Topics: Arrhythmias, Cardiac; Diagnosis, Differential; Electrocardiography; Heart Conduction System; Humans; Severity of Illness Index
PubMed: 29926564
DOI: No ID Found -
Frontiers in Immunology 2021COVID-19 might lead to multi-organ failure and, in some cases, to death. The COVID-19 severity is associated with a "cytokine storm." Danger-associated molecular... (Review)
Review
COVID-19 might lead to multi-organ failure and, in some cases, to death. The COVID-19 severity is associated with a "cytokine storm." Danger-associated molecular patterns (DAMPs) are proinflammatory molecules that can activate pattern recognition receptors, such as toll-like receptors (TLRs). DAMPs and TLRs have not received much attention in COVID-19 but can explain some of the gender-, weight- and age-dependent effects. In females and males, TLRs are differentially expressed, likely contributing to higher COVID-19 severity in males. DAMPs and cytokines associated with COVID-19 mortality are elevated in obese and elderly individuals, which might explain the higher risk for severer COVID-19 in these groups. Adenosine signaling inhibits the TLR/NF-κB pathway and, through this, decreases inflammation and DAMPs' effects. As vaccines will not be effective in all susceptible individuals and as new vaccine-resistant SARS-CoV-2 mutants might develop, it remains mandatory to find means to dampen COVID-19 disease severity, especially in high-risk groups. We propose that the regulation of DAMPs adenosine signaling enhancement might be an effective way to lower the severity of COVID-19 and prevent multiple organ failure in the absence of severe side effects.
Topics: Adenosine; Alarmins; Animals; COVID-19; Humans; Inflammation; Inflammation Mediators; Multiple Organ Failure; Patient Acuity; Signal Transduction; Toll-Like Receptors
PubMed: 34456928
DOI: 10.3389/fimmu.2021.720192 -
Clinical Epigenetics Mar 2024The recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study...
BACKGROUND
The recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome.
METHODS
Whole genome methylation sequencing of cfDNA was performed for 20 healthy individuals, 20 cases with non-hospitalized COVID-19 and 12 cases with severe COVID-19 admitted to intensive care unit (ICU). Differentially methylated regions (DMRs) and gene ontology pathway enrichment analyses were performed to explore the locus-specific methylation difference between cohorts. The proportion of cfDNA derived from lung and immune cells to a given sample (i.e. tissue fraction) at cell-type resolution was estimated using a novel algorithm, which reflects lung injuries and immune response in COVID-19 patients and was further used to evaluate clinical severity and patient outcome.
RESULTS
COVID‑19 patients had globally reduced cfDNA methylation level compared with healthy controls. Compared with non-hospitalized COVID-19 patients, the cfDNA methylation pattern was significantly altered in severe patients with the identification of 11,156 DMRs, which were mainly enriched in pathways related to immune response. Markedly elevated levels of cfDNA derived from lung and more specifically alveolar epithelial cells, bronchial epithelial cells, and lung endothelial cells were observed in COVID-19 patients compared with healthy controls. Compared with non-hospitalized patients or healthy controls, severe COVID-19 had significantly higher cfDNA derived from B cells, T cells and granulocytes and lower cfDNA from natural killer cells. Moreover, cfDNA derived from alveolar epithelial cells had the optimal performance to differentiate COVID-19 with different severities, lung injury levels, SOFA scores and in-hospital deaths, with the area under the receiver operating characteristic curve of 0.958, 0.941, 0.919 and 0.955, respectively.
CONCLUSION
Severe COVID-19 has a distinct cfDNA methylation signature compared with non-hospitalized COVID-19 and healthy controls. Cell type-specific cfDNA methylation signature enables the tracing of COVID-19 related cell deaths in lung and immune cells at cell-type resolution, which is correlated with clinical severities and outcomes, and has extensive application prospects to evaluate tissue injuries in diseases with multi-organ dysfunction.
Topics: Humans; DNA Methylation; Cell-Free Nucleic Acids; Endothelial Cells; COVID-19; ROC Curve
PubMed: 38429730
DOI: 10.1186/s13148-024-01645-7 -
Palliative & Supportive Care Aug 2015Our aim was to examine the characteristics of delirium in the severely medically ill cancer population on the basis of sociodemographic and medical variables, delirium...
OBJECTIVE
Our aim was to examine the characteristics of delirium in the severely medically ill cancer population on the basis of sociodemographic and medical variables, delirium severity, and phenomenology, as well as severity of medical illness.
METHOD
All subjects in the database were recruited from psychiatric referrals at Memorial Sloan Kettering Cancer Center (MSKCC). Sociodemographic and medical variables, as well as the Karnofsky Performance Status (KPS) scale and Memorial Delirium Assessment Scale (MDAS) scores were recorded at baseline. Subsequently, these variables were analyzed with respect to the severity of the medical illness.
RESULTS
Out of 111 patients, 67 qualified as severely medically ill. KPS scores were 19.7 and 30.7 in less severe illness. There were no significant differences with respect to age, history of dementia, and MDAS scores. Although the severity of delirium did not differ, an increased frequency and severity of consciousness disturbance, disorientation, and inability to maintain and shift attention did exist. With respect to etiologies contributing to delirium, hypoxia and infection were commonly associated with severe illness. In contrast, corticosteroid administration was more often associated with less severe illness. There were no differences with respect to opiate administration, dehydration, and CNS disease, including brain metastasis.
SIGNIFICANCE OF RESULTS
Delirium in the severely medically ill cancer population has been characterized by an increased disturbance of consciousness, disorientation, and an inability to maintain and shift attention. However, the severity of illness did not predict severity of delirium. Furthermore, hypoxia and infection were etiologies more commonly associated with delirium in severe illness, whereas the administration of corticosteroids was associated with less severe illness.
Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Delirium; Dementia; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Neoplasms; Severity of Illness Index
PubMed: 25191904
DOI: 10.1017/S1478951514001060 -
International Journal of Molecular... May 2023A spinal cord injury (SCI) initiates a number of cascades of biochemical reactions and intercellular interactions, the outcome of which determines the regenerative...
A spinal cord injury (SCI) initiates a number of cascades of biochemical reactions and intercellular interactions, the outcome of which determines the regenerative potential of the nervous tissue and opens up capacities for preserving its functions. The key elements of the above-mentioned processes are microglia. Many assumptions have been put forward, and the first evidence has been obtained, suggesting that, depending on the severity of SCI and the post-traumatic period, microglia behave differently. In this regard, we conducted a study to assess the microglia behavior in the model of mild, moderate and severe SCI in vitro for various post-traumatic periods. We reported for the first time that microglia make a significant contribution to both anti- and pro-inflammatory patterns for a prolonged period after severe SCI (60 dpi), while reduced severities of SCI do not lead to prolonged activation of microglia. The study also revealed the following trend: the greater the severity of the SCI, the lower the proliferative and phagocytic activity of microglia, which is true for all post-traumatic periods of SCI.
Topics: Humans; Microglia; Spinal Cord Injuries; Spinal Cord
PubMed: 37176001
DOI: 10.3390/ijms24098294 -
Scientific Reports Apr 2021Coronavirus disease 2019 (COVID-19) can present with a variety of symptoms. Severity of the disease may be associated with several factors. Here, we review clinical...
Coronavirus disease 2019 (COVID-19) can present with a variety of symptoms. Severity of the disease may be associated with several factors. Here, we review clinical features of COVID-19 inpatients with different severities. This cross-sectional study was performed in Imam Reza hospital, Mashhad, Iran, during February-April 2020. COVID-19 patients with typical computed tomography (CT) patterns and/or positive reverse-transcriptase polymerase chain reaction (RT-PCR) were included. The patients were classified into three groups of moderate, severe, and critical based on disease severity. Demographic, clinical, laboratory, and radiologic findings were collected and compared. P < 0.05 was considered statistically significant. Overall, 200 patients with mean age of 69.75 ± 6.39 years, of whom 82 (41%) were female were studied. Disease was severe/critical in the majority of patients (167, 83.5%). Disease severity was significantly associated with age, malignant comorbidities, dyspnea, nausea/vomiting, confusion, respiratory rate, pulse rate, O saturation, extent of CT involvement, serum C-reactive protein (CRP), pH, pO, and aspartate transaminase (P < 0.05). Moreover, complications including shock, coagulopathy, acidosis, sepsis, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, and intubation were significantly higher in patients with higher severities (P < 0.05). O saturation, nausea/vomiting, and extent of lung CT involvement were independent predictors of severe/critical COVID-19 (OR 0.342, 45.93, and 25.48, respectively; P < 0.05). Our results indicate O saturation, nausea/vomiting, and extent of lung CT involvement as independent predictors of severe COVID-19 conditions. Serum CRP levels and pO were also considerably higher patients with higher severity and can be used along with other factors to predict severe disease in COVID-19 patients.
Topics: Age Factors; Aged; C-Reactive Protein; COVID-19; Comorbidity; Cross-Sectional Studies; Female; Humans; Inpatients; Iran; Male; Middle Aged; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 33888747
DOI: 10.1038/s41598-021-87917-1 -
Proceedings of the National Academy of... Jan 2023Actin cytoskeleton force generation, sensing, and adaptation are dictated by the bending and twisting mechanics of filaments. Here, we use magnetic tweezers and...
Actin cytoskeleton force generation, sensing, and adaptation are dictated by the bending and twisting mechanics of filaments. Here, we use magnetic tweezers and microfluidics to twist and pull individual actin filaments and evaluate their response to applied loads. Twisted filaments bend and dissipate torsional strain by adopting a supercoiled plectoneme. Pulling prevents plectoneme formation, which causes twisted filaments to sever. Analysis over a range of twisting and pulling forces and direct visualization of filament and single subunit twisting fluctuations yield an actin filament torsional persistence length of ~10 µm, similar to the bending persistence length. Filament severing by cofilin is driven by local twist strain at boundaries between bare and decorated segments and is accelerated by low pN pulling forces. This work explains how contractile forces generated by myosin motors accelerate filament severing by cofilin and establishes a role for filament twisting in the regulation of actin filament stability and assembly dynamics.
Topics: Actin Cytoskeleton; Cytoskeleton; Actin Depolymerizing Factors; Myosins; Protein Binding; Actins
PubMed: 36656858
DOI: 10.1073/pnas.2208536120 -
Nutrition & Diabetes Jun 2017This retrospective, population-based, cross-sectional study evaluated the association between vitamin D deficiency and retinopathy severity in diabetic patients with...
OBJECTIVES
This retrospective, population-based, cross-sectional study evaluated the association between vitamin D deficiency and retinopathy severity in diabetic patients with poorly or well controlled glycaemia. Other potential risk factors for diabetic retinopathy severity were also assessed.
METHODS
The National Health and Nutrition Examination Survey (NHANES) 2005-2008 data were used for the study. Outcomes assessed included retinopathy severity, HbA1c levels, socioeconomic, behavioral, and biological factors. Univariate and multivariate regression analysis was used to evaluate association of different parameters with retinopathy severity. The interaction among HbA1c control, vitamin D deficiency, and retinopathy severity were also explored.
RESULTS
The population included 842 adults (52.8% women) with mean age of 61.2 years. Retinopathy was detected in 301 subjects (35.7%). Mild non-proliferative retinopathy (NPR) was present in 195 subjects (23.2%), severe non-proliferative and proliferative retinopathy in 106 subjects (12.6%). Multivariate ordinal regression analysis found being male (odds ratio (OR): 1.602, P=0.001), increased duration of diabetes (OR: 1.072, P=3.77E-7) and poorly controlled HbA1c (OR: 3.522, P=2.00E-5) were associated with greater retinopathy severity. The association between vitamin D deficiency and retinopathy severity only found in diabetic patients with well controlled glycaemia.
CONCLUSIONS
The findings of this study indicate that vitamin D deficiency associated with severe diabetic retinopathy in patients with well controlled diabetes. The findings provide possible relationship for the previous conflict results, and highlight the need for controlling modifiable risk factors to reduce the development of sever diabetic retinopathy.
Topics: Cross-Sectional Studies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Nutrition Surveys; Retrospective Studies; Severity of Illness Index; United States; Vitamin D
PubMed: 28604686
DOI: 10.1038/nutd.2017.30 -
The World Allergy Organization Journal Feb 2022Asthma is a heterogeneous inflammatory airway disorder with various phenotypes. Quantitative computed tomography (QCT) methods can differentiate among lung diseases...
BACKGROUND
Asthma is a heterogeneous inflammatory airway disorder with various phenotypes. Quantitative computed tomography (QCT) methods can differentiate among lung diseases through accurate assessment of the location, extent, and severity of the disease. The purpose of this study was to identify asthma clusters using QCT metrics of airway and parenchymal structure, and to identify associations with visual analyses conducted by radiologists.
METHODS
This prospective study used input from QCT-based metrics including hydraulic diameter ( ), luminal wall thickness (WT), functional small airway disease (fSAD), and emphysematous lung (Emph) to perform a cluster analysis and made comparisons with the visual grouping analysis conducted by radiologists based on site of airway involvement and remodeling evaluated.
RESULTS
A total of 61 asthmatics of varying severities were grouped into 4 clusters. From C1 to C4, more severe lung function deterioration, higher fixed obstruction rate, and more frequent asthma exacerbations were observed in the 5-year follow-up period. C1 presented non-severe asthma with increased WT, of proximal airways, and fSAD. C2 was mixed with non-severe and severe asthmatics, and showed bronchodilator responses limited to the proximal airways. C3 and C4 included severe asthmatics that showed a reduced of the proximal airway and diminished bronchodilator responses. While C3 was characterized by severe allergic asthma without fSAD, C4 included ex-smokers with high fSAD% and Emph%. These clusters correlated well with the grouping done by radiologists and clinical outcomes.
CONCLUSIONS
Four QCT imaging-based clusters with distinct structural and functional changes in proximal and small airways can stratify heterogeneous asthmatics and can be a complementary tool to predict clinical outcomes.
PubMed: 36091187
DOI: 10.1016/j.waojou.2022.100628