ResearchPad - state-of-the-art https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Inherited Thoracic Aortic Disease]]> https://www.researchpad.co/article/elastic_article_8313 Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions.

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<![CDATA[Severe acute respiratory syndrome in children]]> https://www.researchpad.co/article/Nbf0d42d5-ef27-429e-a56f-0460e4ee87c1

Abstract

Severe acute respiratory syndrome (SARS) is a newly described and highly contagious respiratory infection. Many adult patients will develop progressive hypoxia, and a large proportion will develop respiratory distress syndrome (RDS), possibly related to massive and uncontrolled activation of the immune system. The mortality has been reported to be quite high, especially in the elderly with comorbid conditions. The causative agent has been identified as a novel coronavirus, and children appear to acquire the infection by close‐contact household exposure to an infected adult. However, the severity is much milder and the clinical progression much less aggressive in young children. The exact pathophysiology of SARS is still unclear, and the medical treatment of SARS remains controversial. The main treatment regime used in Hong Kong is a combination of ribavirin and steroid. To date, there have been no reported case fatalities in children with this disease. The success of reducing the burden of this infection in children will depend on proper isolation of infected adults early in the course of illness. Strict public health policy and quarantine measures are the key in controlling the infection in the community. Pediatr Pulmonol. 2003; 36:261–266. © 2003 Wiley‐Liss, Inc.

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<![CDATA[Acute Community-Acquired Sinusitis]]> https://www.researchpad.co/article/N21715625-d417-44dc-8f36-0e23cbeeae67 ]]> <![CDATA[Iron and Heart Failure]]> https://www.researchpad.co/article/N88483ef8-1e58-44e9-a46b-d99f71d84f29

Highlights

  • Intravenous iron supplementation provides symptomatic relief in patients with heart failure and concomitant iron deficiency.

  • The current definition of iron deficiency based on ferritin <100 ng/ml or transferrin saturation <20% may not accurately reflect the levels of iron within tissue and cells. Therefore, intravenous iron may be administered to heart failure patients who do not require iron supplementation.

  • Intravenous administration of iron bypasses essential regulatory mechanisms and can cause endothelial damage via the production of reactive oxygen species.

  • Although iron should be given to patients with heart failure and iron deficiency, sufficient consideration should be given to the route of administration and the potential for adverse effects, especially in non–iron deficient patients.

  • Further research must be conducted to determine whether changes in the cellular and subcellular distribution of iron in patients with heart failure are compensatory and beneficial or maladaptive and potentiates disease.

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<![CDATA[A long journey for acute kidney injury biomarkers]]> https://www.researchpad.co/article/N5609cc71-50f5-49e5-9158-4c4638caa781

Abstract

Acute kidney injury (AKI) is a life-threatening illness that continues to have an in-hospital mortality rate of patients with AKI ranges from 20% to 50% or greater, depending on underlying conditions. However, it has only marginally declined over the past 25 years. Previous authoritative publications have been pointed out that the lack of useful biomarkers for AKI has limited progress in improving the outcomes of this disorder. The purpose of this paper is to review the recent biomarkers involved in the early detection of AKI and main reasons for the failure to identify new AKI biomarkers. So far, several new AKI biomarkers have been discovered and validated to improve early diagnosis, degree of severity, pathophysiology, differential diagnosis, prediction for major kidney adverse events (MAKE, risk groups for progressive renal failure, need for renal replacement therapy [RRT], or death). These biomarkers can be classified into functional, damage and pre-injury phase biomarkers. However, the clinical use of the studied biomarkers in AKI prediction remains unclear because large prospective multicenter trials have failed to demonstrate troponin-like diagnostic performance. Reasons for the failure to identify AKI biomarkers are the heterogeneity of AKI itself, biomarker limitations and long roads to the validation of candidates for new AKI biomarkers. In an effort to overcome these barriers to identifying new AKI biomarkers, kidney biopsy specimens should be obtained and assessed in human AKI populations. Research in this field should be carried out in a pan-social approach rather than conducted by just a few medical institutions.

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<![CDATA[Clonal Hematopoiesis: A New Step Linking Inflammation to Heart Failure]]> https://www.researchpad.co/article/N96298ecf-95b2-4571-a218-79566df707d9

Highlights

  • Clonal hematopoiesis is a common condition in the elderly that can result from the acquisition of somatic mutations in HSPCs that confer a selective advantage and allow for clonal cell expansion.

  • This clonal population of mutated HSPCs can give rise to leukocytes with altered immune properties, and this condition can adversely impact the cardiovascular system.

  • Clonal hematopoiesis may represent a new causal risk factor for cardiovascular disease that can add to the predictive value of the traditional risk factors.

  • Understanding the clonal hematopoiesis status of a patient could aid in the development of personalized strategies for anti-inflammatory therapies for cardiovascular disease.

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<![CDATA[Targeting the Mitochondria in Heart Failure]]> https://www.researchpad.co/article/N97c40d85-aac0-4cf9-aa43-bb87467b2b47

Visual Abstract

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<![CDATA[Renal microvascular lesions in lupus nephritis]]> https://www.researchpad.co/article/Nd1c12f58-731d-435d-95c1-303b4b0383a7

Abstract

Renal microvascular lesions, common in lupus nephritis (LN), are associated with long-term poor outcomes. There are mainly five pathological types of renal microvascular lesions in LN: (1) vascular immune complex deposits (ICD), (2) arteriosclerosis (AS), (3) thrombotic microangiopathy (TMA), (4) non-inflammatory necrotizing vasculopathy (NNV), and (5) true renal vasculitis (TRV). The pathogenesis of renal microvascular lesions in LN remains to be elucidated. The activation and dysfunction of endothelial cells, in addition to the contribution of immune system dysfunction, especially the immune complex-induced vascular inflammation and antiphospholipid antibody-associated thrombotic events, are key mechanisms in the development of vascular lesions in LN that need to be further investigated. Alteration of the microvascular environment produces an acute immunological response that recruits immune cells, such as T cells, monocytes, and macrophages, which induces platelet aggregation with microthrombus formation. There is also increased cytotoxicity caused by cytokines produced by immune cells in the kidney. Identifying the mechanism underlying the pathogenesis of renal microvascular lesions in LN might provide potential targets for the development of novel therapies.

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<![CDATA[Acquired long QT syndrome in chronic kidney disease patients]]> https://www.researchpad.co/article/N16099e27-044e-4ca4-9b83-ee59c45bf376

Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients. QT interval prolongation is a congenital or acquired condition that is associated with an increased risk of torsade de pointes (TdP), sudden cardiac death (SCD), and all-cause mortality in the general population. The prevalence of acquired long QT syndrome (aLQTS) is high, and various acquired conditions contribute to the prolonged QT interval in patients with CKD. More notably, the prolonged QT interval in CKD is an independent risk factor for SCD and all-cause mortality. In this review, we focus on the epidemiological characteristics, risk factors, underlying mechanisms and treatments of aLQTS in CKD, promoting the management of aLQTS in CKD patients.

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<![CDATA[Telomeres as Therapeutic Targets in Heart Disease]]> https://www.researchpad.co/article/N2f68b83e-3286-455c-be72-b857e192985f

Highlights

  • Age-associated CVDs impose a great burden on current health systems. Despite the fact that current strong evidence supports the links among aging, telomere attrition, and CVDs, there is no clear direction for the development of telomere therapeutics against CVDs.

  • This review focuses on immune modulation, CHIP, pharmaceutical interventions, and gene therapy for their therapeutic roles in age-associated CVDs.

  • The future goal of telomere cardiovascular therapy in young subjects is to prevent senescence and diseases, whereas in older adult subjects, the goal is restoration of cardiovascular functions. Further studies on the telomere-CHIP-atherosclerosis axis may shed insights on how to achieve these 2 different therapeutic targets.

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<![CDATA[Assessment and Treatment of Patients With Type 2 Myocardial Infarction and Acute Nonischemic Myocardial Injury]]> https://www.researchpad.co/article/N2633c474-6b5a-4415-b5cc-ae9483bec0bb

Supplemental Digital Content is available in the text.

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<![CDATA[Genes Associated with Thoracic Aortic Aneurysm and Dissection: 2019 Update and Clinical Implications]]> https://www.researchpad.co/article/Naf022138-2ea6-4200-ba87-51058f036815

Thoracic aortic aneurysm is a typically silent disease characterized by a lethal natural history. Since the discovery of the familial nature of thoracic aortic aneurysm and dissection (TAAD) almost 2 decades ago, our understanding of the genetics of this disorder has undergone a transformative amplification. To date, at least 37 TAAD-causing genes have been identified and an estimated 30% of the patients with familial nonsyndromic TAAD harbor a pathogenic mutation in one of these genes. In this review, we present our yearly update summarizing the genes associated with TAAD and the ensuing clinical implications for surgical intervention. Molecular genetics will continue to bolster this burgeoning catalog of culprit genes, enabling the provision of personalized aortic care.

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<![CDATA[Achieving Mucosal Healing in Inflammatory Bowel Diseases: Which Drug Concentrations Need to Be Targeted?]]> https://www.researchpad.co/article/N77cfaf86-13a8-4448-8d54-a8a0015d05f7

Biologicals introduced a major shift in the treatment of patients suffering from inflammatory bowel diseases. Despite providing a tight disease control for many patients, a considerable proportion of patients will fail to respond favorably to treatment or will lose response over time. Therapeutic drug monitoring emerged as a valuable tool to guide clinical decision making as serum drug concentrations have been linked to outcomes. Focusing on mucosal healing as the ultimate treatment goal, different drug concentration thresholds to achieve this outcome have been identified in the literature and are summarized in this review. For therapeutic drug monitoring to be successful in guiding clinical decision making, the used assay, the sampling time point, and the outcome that is aimed for should be taken into account when interpreting drug concentration thresholds. Awareness of these essential aspects among clinicians will improve the implementation of therapeutic drug monitoring and aid in making an evidence‐based decision.

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<![CDATA[Metabolic Concepts in Idiopathic Intracranial Hypertension and Their Potential for Therapeutic Intervention]]> https://www.researchpad.co/article/5c94e6ced5eed0c48465332c

Background:

Traditional risk factors associated with idiopathic intracranial hypertension (IIH) include obesity, weight gain, and female sex. The incidence of IIH is increasing and yet the underlying trigger and the fueling pathological mechanisms are still poorly understood.

Evidence Acquisition:

Review of ophthalmology, neurology, general surgery, obesity, endocrinology, nutrition, and neurosurgery literature was made.

Results:

The facts that implicate sex and obesity in IIH and headache are examined. The role of fat distribution in IIH is questioned, and the concept of adipose tissue functioning as an endocrine organ driving IIH is discussed. The impact of androgen metabolism in IIH is reviewed as is the emerging role of glucagon-like-peptide-1 analogues in modulating intracranial pressure. This introduces the concept of developing targeted disease-modifying therapeutic strategies for IIH.

Conclusions:

This review will discuss the possible role of the adipose/gut/brain metabolism axis in IIH and speculate how this may impact the pathogenesis of IIH and therapeutic opportunities.

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<![CDATA[Imaging Cancer Metabolism: Underlying Biology and Emerging Strategies]]> https://www.researchpad.co/article/5c8ef057d5eed0c484f03409

Dysregulated cellular metabolism is a characteristic feature of malignancy that has been exploited for both imaging and targeted therapy. With regard to imaging, deranged glucose metabolism has been leveraged using 18F-FDG PET. Metabolic imaging with 18F-FDG, however, probes only the early steps of glycolysis; the complexities of metabolism beyond these early steps in this single pathway are not directly captured. New imaging technologies—both PET with novel radiotracers and MR-based methods—provide unique opportunities to investigate other aspects of cellular metabolism and expand the metabolic imaging armamentarium. This review will discuss the underlying biology of metabolic dysregulation in cancer, focusing on glucose, glutamine, and acetate metabolism. Novel imaging strategies will be discussed within this biologic framework, highlighting particular strengths and limitations of each technique. Emphasis is placed on the role that combining modalities will play in enabling multiparametric imaging to fully characterize tumor biology to better inform treatment.

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<![CDATA[Renal structural image processing techniques: a systematic review]]> https://www.researchpad.co/article/5c801531d5eed0c484a9ee40

Abstract

Background and objective: Renal disease, such as nephritis and nephropathy, is very harmful to human health. Accordingly, how to achieve early diagnosis and enhance treatment for kidney disorders would be the important lesion. Nevertheless, the clues from the clinical data, such as biochemistry examination, serological examination, and radiological studies are quite indirect and limited. It is no doubt that pathological examination of kidney will supply the direct evidence. There is a requirement for greater understanding of image processing techniques for renal diagnosis to optimize treatment and patient care.

Methods: This study aims to systematically review the literature on publications that has been used image processing methods on pathological microscopic image for renal diagnosis.

Results: Nine included studies revealed image analysis techniques for the diagnosis of renal abnormalities on pathological microscopic image, renal image studies are clustered as follows: Glomeruli Segmentation and analysis of the Glomerular basement membrane (55/55%), Blood vessels and tubules classification and detection (22/22%) and The Grading of renal cell carcinomas (22/22%).

Conclusions: A medical image analysis method should provide an auto-adaptive and no external-human action dependency. In addition, since medical systems should have special characteristics such as high accuracy and reliability then clinical validation is highly recommended. New high-quality studies based on Moore neighborhood contour tracking method for glomeruli segmentation and using powerful texture analysis techniques such as the local binary pattern are recommended.

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<![CDATA[Issues and developments related to assessing function in serious mental illness]]> https://www.researchpad.co/article/5b00f59b463d7e3e69037d42

Serious mental illness (SMI) results in functional disability that imposes a significant burden on individuals, caregivers, and society. Development of novel treatments is under way in an effort to improve the illness domains of cognitive impairment and negative symptoms and subsequently to improve functional outcomes. The assessment of functional outcomes in SMI faces a number of challenges, including the proliferation of assessment instruments and the differential prioritization of functional goals among stakeholder groups. Functional assessments relying on self- and informant report present a number of limitations. Identifying alternative strategies to assess functioning that are reliable, valid, and sensitive to change is necessary for use in clinical trials. Measures of functional capacity have been proposed for clinical trials investigating compounds to treat cognitive impairment in schizophrenia. Alternative approaches employing effort-based decision making or daily activity recording using instruments such as the Daily Activity Report may be more appropriate for studies focused on improving negative symptoms.

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<![CDATA[Non invasive ventilation as an additional tool for exercise training]]> https://www.researchpad.co/article/5989db15ab0ee8fa60bccf28

Recently, there has been increasing interest in the use of non invasive ventilation (NIV) to increase exercise capacity. In individuals with COPD, NIV during exercise reduces dyspnoea and increases exercise tolerance.

Different modalities of mechanical ventilation have been used non-invasively as a tool to increase exercise tolerance in COPD, heart failure and lung and thoracic restrictive diseases. Inspiratory support provides symptomatic benefit by unloading the ventilatory muscles, whereas Continuous Positive Airway Pressure (CPAP) counterbalances the intrinsic positive end-expiratory pressure in COPD patients.

Severe stable COPD patients undergoing home nocturnal NIV and daytime exercise training showed some benefits. Furthermore, it has been reported that in chronic hypercapnic COPD under long-term ventilatory support, NIV can also be administered during walking.

Despite these results, the role of NIV as a routine component of pulmonary rehabilitation is still to be defined.

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<![CDATA[Advances in the diagnosis and management of diabetic distal symmetric polyneuropathy]]> https://www.researchpad.co/article/5ad5839b463d7e44c1f217f9

Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of diabetes mellitus. The pathogenesis of DSPN is not fully elucidated, but it is certainly multifactorial in nature and attributable to metabolic and microvessel disorders related to chronic hyperglycemia, diabetes duration, and several cardiovascular risk factors. Early diagnosis and appropriate management are extremely important, since up to 50% of DSPN cases may be asymptomatic, and patients are unaware of foot injury leading to foot ulcers and amputation. Simple, validated tests such as the Neuropathy Disability Score and/or Vibration Perception Threshold may be used to diagnose DSPN. Similarly, neurological dysfunction screening questionnaires should be used to assess the quality and severity of DSPN symptoms. Using both methods enables prediction of the prognosis of diabetic patients with DSPN. No causative treatment of DSPN is known, but the results of clinical trials indicate that several treatment options are highly effective in symptomatic treatment of painful DSPN. The appropriate treatment of DSPN may improve the outcome, preventing or delaying the development of numerous diabetic complications.

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<![CDATA[Glycoprotein VI in securing vascular integrity in inflamed vessels]]> https://www.researchpad.co/article/5c083384d5eed0c484f9a280

Abstract

Essentials

  • Platelets can stop bleeding independently of integrin‐mediated aggregation in inflamed organs.

  • GPVI contributes to aggregation‐independent hemostasis in the inflamed skin.

  • GPVI supports sealing of neutrophil‐induced vascular breaches by nonaggregated platelets.

  • Evaluation of anti‐GPVI drugs should take into account the risk of inflammatory bleeding.

Glycoprotein VI (GPVI), the main platelet receptor for collagen, has been shown to play a central role in various models of thrombosis, and to be a minor actor of hemostasis at sites of trauma. These observations have made of GPVI a novel target for antithrombotic therapy, as its inhibition would ideally combine efficacy with safety. Nevertheless, recent studies have indicated that GPVI could play an important role in preventing bleeding caused by neutrophils in the inflamed skin and lungs. Remarkably, there is evidence that the GPVI‐dependent hemostatic function of platelets at the acute phase of inflammation in these organs does not involve aggregation. From a therapeutic perspective, the vasculoprotective action of GPVI in inflammation suggests that blocking of GPVI might bear some risks of bleeding at sites of neutrophil infiltration. In this review, we summarize recent findings on GPVI functions in inflammation and discuss their possible clinical implications and applications.

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