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Nature Reviews. Disease Primers Mar 2020Acute heart failure (AHF) is a syndrome defined as the new onset (de novo heart failure (HF)) or worsening (acutely decompensated heart failure (ADHF)) of symptoms and... (Review)
Review
Acute heart failure (AHF) is a syndrome defined as the new onset (de novo heart failure (HF)) or worsening (acutely decompensated heart failure (ADHF)) of symptoms and signs of HF, mostly related to systemic congestion. In the presence of an underlying structural or functional cardiac dysfunction (whether chronic in ADHF or undiagnosed in de novo HF), one or more precipitating factors can induce AHF, although sometimes de novo HF can result directly from the onset of a new cardiac dysfunction, most frequently an acute coronary syndrome. Despite leading to similar clinical presentations, the underlying cardiac disease and precipitating factors may vary greatly and, therefore, the pathophysiology of AHF is highly heterogeneous. Left ventricular diastolic or systolic dysfunction results in increased preload and afterload, which in turn lead to pulmonary congestion. Fluid retention and redistribution result in systemic congestion, eventually causing organ dysfunction due to hypoperfusion. Current treatment of AHF is mostly symptomatic, centred on decongestive drugs, at best tailored according to the initial haemodynamic status with little regard to the underlying pathophysiological particularities. As a consequence, AHF is still associated with high mortality and hospital readmission rates. There is an unmet need for increased individualization of in-hospital management, including treatments targeting the causative factors, and continuation of treatment after hospital discharge to improve long-term outcomes.
Topics: Fluid Shifts; Heart Failure; Humans; Risk Factors
PubMed: 32139695
DOI: 10.1038/s41572-020-0151-7 -
Nutrients Jan 2020Food is often considered to be a precipitating factor of irritable bowel syndrome (IBS) symptoms. In recent years, there has been a growing interest in FODMAPs... (Review)
Review
Food is often considered to be a precipitating factor of irritable bowel syndrome (IBS) symptoms. In recent years, there has been a growing interest in FODMAPs (Fermentable Oligo-, Di-, Mono-saccharides, And Polyols), which can be found in many common foods. A low FODMAP diet (LFD) is increasingly suggested for IBS treatment. However, long-term, large, randomized controlled studies are still lacking, and certainties and doubts regarding LFDs have grown, often in a disorderly and confused manner. Some potential LFD limitations and concerns have been raised, including nutritional adequacy, cost, and difficulty in teaching the diet and maintaining it. Most of these limitations can be solved with the involvement of a skilled nutritionist, who can clearly explain the different phases of the LFD and ensure nutritional adequacy and compliance. Further studies should focus on new methods of teaching and learning the LFD and on predictors of response. Moreover, particular interest should be focused on the possible use of LFD in gastrointestinal diseases other than functional disorders and, possibly, also in non-gastrointestinal diseases. The aim of the present review was to clarify the effective and appropriate indications and limitations of an LFD and to discuss its possible future uses.
Topics: Diet, Carbohydrate-Restricted; Disaccharides; Fermentation; Food Analysis; Humans; Irritable Bowel Syndrome; Monosaccharides; Oligosaccharides; Polymers
PubMed: 31947991
DOI: 10.3390/nu12010148 -
Frontiers in Clinical Diabetes and... 2021Diabetes mellitus (DM) affects the metabolism of primary macronutrients such as proteins, fats, and carbohydrates. Due to the high prevalence of DM, emergency admissions... (Review)
Review
Diabetes mellitus (DM) affects the metabolism of primary macronutrients such as proteins, fats, and carbohydrates. Due to the high prevalence of DM, emergency admissions for hyperglycemic crisis, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are fairly common and represent very challenging clinical management in practice. DKA and HHS are associated with high mortality rates if left not treated. The mortality rate for patients with DKA is < 1% and ~ 15% for HHS. DKA and HHS have similar pathophysiology with some few differences. HHS pathophysiology is not fully understood. However, an absolute or relative effective insulin concentration reduction and increased in catecholamines, cortisol, glucagon, and growth hormones represent the mainstay behind DKA pathophysiology. Reviewing the patient's history to identify and modify any modifiable precipitating factors is crucial to prevent future events. The aim of this review article is to provide a review of the DKA, and HHS management based on the most recently published evidence and to provide suggested management pathway of DKA of HHS management in practice.
PubMed: 36994324
DOI: 10.3389/fcdhc.2021.820728 -
Genome Biology Apr 2023Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying...
BACKGROUND
Ocular neovascularization is a leading cause of blindness. Retinal microglia have been implicated in hypoxia-induced angiogenesis and vasculopathy, but the underlying mechanisms are not entirely clear. Lactylation is a novel lactate-derived posttranslational modification that plays key roles in multiple cellular processes. Since hypoxia in ischemic retinopathy is a precipitating factor for retinal neovascularization, lactylation is very likely to be involved in this process. The present study aimed to explore the role of lactylation in retinal neovascularization and identify new therapeutic targets for retinal neovascular diseases.
RESULTS
Microglial depletion by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 suppresses retinal neovascularization in oxygen-induced retinopathy. Hypoxia increased lactylation in microglia and accelerates FGF2 expression, promoting retinal neovascularization. We identify 77 sites of 67 proteins with increased lactylation in the context of increased lactate under hypoxia. Our results show that the nonhistone protein Yin Yang-1 (YY1), a transcription factor, is lactylated at lysine 183 (K183), which is regulated by p300. Hyperlactylated YY1 directly enhances FGF2 transcription and promotes angiogenesis. YY1 mutation at K183 eliminates these effects. Overexpression of p300 increases YY1 lactylation and enhances angiogenesis in vitro and administration of the p300 inhibitor A485 greatly suppresses vascularization in vivo and in vitro.
CONCLUSIONS
Our results suggest that YY1 lactylation in microglia plays an important role in retinal neovascularization by upregulating FGF2 expression. Targeting the lactate/p300/YY1 lactylation/FGF2 axis may provide new therapeutic targets for proliferative retinopathies.
Topics: Animals; Mice; Fibroblast Growth Factor 2; Hypoxia; Lactates; Microglia; Protein Processing, Post-Translational; Retinal Neovascularization; Transcriptional Activation; Up-Regulation; YY1 Transcription Factor
PubMed: 37085894
DOI: 10.1186/s13059-023-02931-y -
Annals of Hepatology 2022Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%-40% of patients with cirrhosis will present... (Review)
Review
Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%-40% of patients with cirrhosis will present overt HE during their lifetime. While the pathophysiology of HE is not entirely understood, three critical factors have been identified: hyperammonaemia, systemic inflammation and oxidative stress by glutaminase gene alterations. Minimal HE is defined by the presence of signs of cognitive abnormalities in a patient without asterixis or disorientation; it can only be diagnosed with neuropsychological or psychometric tests. The diagnosis of overt HE is based on clinical examination with clinical scales. Currently, only overt HE should be routinely treated. The aims of treatment in an acute episode should be to improve the mental status, identify and treat the precipitating factor, reduce duration and limit consequences. Treatment strategies are targeted at reducing ammonia production and/or increasing its elimination. Even though minimal HE has negative effects on the patient's quality of life and effects on prognosis, indications for treatment are still controversial. There are still many unanswered questions regarding the pathophysiology and management of HE. We should also endeavor to develop more accurate and objective diagnostic methods for overt HE that would permit early detection and help improve outcomes on quality of life and economic burden.
Topics: Humans; Hepatic Encephalopathy; Quality of Life; Liver Cirrhosis; Hyperammonemia; Psychometrics
PubMed: 36115576
DOI: 10.1016/j.aohep.2022.100757 -
Clinical Implant Dentistry and Related... Aug 2023Peri-implant mucosal integration is becoming a critical aspect for long term implant health and can be triggered the selection of implant components. The aim of this... (Review)
Review
Peri-implant mucosal integration is becoming a critical aspect for long term implant health and can be triggered the selection of implant components. The aim of this review is therefore to investigate the evidence concerning implant connection and abutment characteristics (abutment materials, design, handling) as predisposing or precipitating factor for peri-implant mucositis and peri-implantitis. Although the evidence that these features can directly predispose/precipitate peri-implant diseases is limited, there are -few- studies showing a potential role of the implant connection, trans-mucosal configuration, and handling in the development of early bone loss and/or peri-implantitis. With bone level implants, conical internal connections (with inherent platform switching) might be preferred over internal flat-flat and external connections to decrease the risk of early bone loss and potentially the risk of peri-implant disease. Moreover, there is a trend suggesting moving the prosthetic interface coronally (to the juxta-mucosal level) as soon as possible to reduce the number of disconnections and to limit the risk of cements remnants. This can be achieved by choosing a tissue-level implant or to place a trans-mucosal abutment (one abutment-one time approach) to optimize the peri-implant soft tissue seal. In absence of evidence for the biocompatibility regarding several restorative materials, biocompatible materials such as titanium or zirconia should be preferred in the trans-mucosal portion. Finally, higher implants (≥2mm) with an emergence angle below 30° seem more favourable. It should however be noted that some of this information is solely based on indirect information (such as early bone loss) and more research is needed before making firm recommendations about abutment choice. [Correction added on 13 March 2023, after first online publication: 'longer implants (≥2mm)' was changed to 'higher implants (≥2mm)' in this version.].
Topics: Humans; Peri-Implantitis; Dental Implants; Dental Implant-Abutment Design; Precipitating Factors; Dental Abutments
PubMed: 36825512
DOI: 10.1111/cid.13185 -
Journal of Translational Internal... Dec 2020Type C hepatic encephalopathy (HE) is a brain dysfunction caused by severe hepatocellular failure or presence of portal-systemic shunts in patients with liver cirrhosis.... (Review)
Review
Type C hepatic encephalopathy (HE) is a brain dysfunction caused by severe hepatocellular failure or presence of portal-systemic shunts in patients with liver cirrhosis. In its subclinical form, called "minimal hepatic encephalopathy (MHE), only psychometric tests or electrophysiological evaluation can reveal alterations in attention, working memory, psychomotor speed and visuospatial ability, while clinical neurological signs are lacking. The term "covert" (CHE) has been recently used to unify MHE and Grade I HE in order to refer to a condition that is not unapparent but also non overt. "Overt" HE (OHE) is characterized by personality changes, progressive disorientation in time and space, acute confusional state, stupor and coma. Based on its time course, OHE can be divided in Episodic, Recurrent or Persistent. Episodic HE is generally triggered by one or more precipitant factors that should be found and treated. Unlike MHE, clinical examination and clinical decision are crucial for OHE diagnosis and West Haven criteria are widely used to assess the severity of neurological dysfunction. Primary prophylaxis of OHE is indicated only in the patient with gastrointestinal bleeding using non-absorbable antibiotics (Rifaximin) or non-absorbable disaccharides (Lactulose). Treatment of OHE is based on the identification and correction of precipitating factors and starting empirical ammonia-lowering treatment with Rifaximin and Lactulose (per os and enemas). The latter should be used for secondary prophylaxis, adding Rifaximin if HE becomes recurrent. In recurrent/persistent HE, the treatment options include fecal transplantation, TIPS revision and closure of eventual splenorenal shunts. Treatment of MHE should be individualized on a case-by-case basis.
PubMed: 33511048
DOI: 10.2478/jtim-2020-0034 -
JAMA Network Open Jan 2023Despite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the...
IMPORTANCE
Despite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups.
OBJECTIVE
To conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting.
EVIDENCE REVIEW
A literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium.
FINDINGS
A total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity.
CONCLUSIONS AND RELEVANCE
In this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium's heterogeneous pathophysiology and treatment.
Topics: Adult; Humans; Male; Female; Disease Susceptibility; Delirium; Precipitating Factors; Prospective Studies; Case-Control Studies
PubMed: 36607634
DOI: 10.1001/jamanetworkopen.2022.49950 -
The Journal of Clinical Investigation Sep 2021The heart forms early in development and delivers oxygenated blood to the rest of the embryo. After birth, the heart requires kilograms of ATP each day to support... (Review)
Review
The heart forms early in development and delivers oxygenated blood to the rest of the embryo. After birth, the heart requires kilograms of ATP each day to support contractility for the circulation. Cardiac metabolism is omnivorous, utilizing multiple substrates and metabolic pathways to produce this energy. Cardiac development, metabolic tuning, and the response to ischemia are all regulated in part by the hypoxia-inducible factors (HIFs), central components of essential signaling pathways that respond to hypoxia. Here we review the actions of HIF1, HIF2, and HIF3 in the heart, from their roles in development and metabolism to their activity in regeneration and preconditioning strategies. We also discuss recent work on the role of HIFs in atherosclerosis, the precipitating cause of myocardial ischemia and the leading cause of death in the developed world.
Topics: Animals; Atherosclerosis; Basic Helix-Loop-Helix Transcription Factors; Heart; Humans; Hypoxia-Inducible Factor 1; Ischemic Preconditioning, Myocardial; Metabolic Networks and Pathways; Mice; Mice, Knockout; Models, Cardiovascular; Myocardial Ischemia; Myocardium; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 34623330
DOI: 10.1172/JCI137557 -
Headache Jul 2020Migraine is a disabling primary headache disorder often associated with triggers. Diet-related triggers are a common cause of migraine and certain diets have been...
BACKGROUND
Migraine is a disabling primary headache disorder often associated with triggers. Diet-related triggers are a common cause of migraine and certain diets have been reported to decrease the frequency of migraine attacks if dietary triggers or patterns are adjusted.
OBJECTIVE
The systematic literature review was conducted to qualitatively summarize evidence from the published literature regarding the role of diet patterns, diet-related triggers, and diet interventions in people with migraine.
METHODS
A literature search was carried out on diet patterns, diet-related triggers, and diet interventions used to treat and/or prevent migraine attacks, using an a priori protocol. MEDLINE and EMBASE databases were searched to identify studies assessing the effect of diet, food, and nutrition in people with migraine aged ≥18 years. Only primary literature sources (randomized controlled trials or observational studies) were included and searches were conducted from January 2000 to March 2019. The NICE checklist was used to assess the quality of the included studies of randomized controlled trials and the Downs and Black checklist was used for the assessment of observational studies.
RESULTS
A total of 43 studies were included in this review, of which 11 assessed diet patterns, 12 assessed diet interventions, and 20 assessed diet-related triggers. The overall quality of evidence was low, as most of the (68%) studies assessing diet patterns and diet-related triggers were cross-sectional studies or patient surveys. The studies regarding diet interventions assessed a variety of diets, such as ketogenic diet, elimination diets, and low-fat diets. Alcohol and caffeine uses were the most common diet patterns and diet-related triggers associated with increased frequency of migraine attacks. Most of the diet interventions, such as low-fat and elimination diets, were related to a decrease in the frequency of migraine attacks.
CONCLUSIONS
There is limited high-quality randomized controlled trial data on diet patterns or diet-related triggers. A few small randomized controlled trials have assessed diet interventions in preventing migraine attacks without strong results. Although many patients already reported avoiding personal diet-related triggers in their migraine management, high-quality research is needed to confirm the effect of diet in people with migraine.
Topics: Diet; Diet Therapy; Feeding Behavior; Humans; Migraine Disorders; Precipitating Factors
PubMed: 32449944
DOI: 10.1111/head.13836