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Frontiers in Neurology 2023The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD...
BACKGROUND/OBJECTIVES
The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD in adults is difficult, because phenotypes are different from those in children and influenced by symptoms from acquired conditions. This systematic literature review aims to answer the following questions: (1) What is the diagnostic yield of exome/genome sequencing (ES/GS) for IMD in adults with unsolved phenotypes? (2) What characteristics do adult patients diagnosed with IMD through ES/GS have?
METHODS
A systematic search was conducted using the following search terms (simplified): "Whole exome sequencing (WES)," "Whole genome sequencing (WGS)," "IMD," "diagnostics" and the 1,450 known metabolic genes derived from ICIMD. Data from 695 articles, including 27,702 patients, were analyzed using two different methods. First, the diagnostic yield for IMD in patients presenting with a similar phenotype was calculated. Secondly, the characteristics of patients diagnosed with IMD through ES/GS in adulthood were established.
RESULTS
The diagnostic yield of ES and/or GS for adult patients presenting with unexplained neurological symptoms is 11% and for those presenting with dyslipidemia, diabetes, auditory and cardiovascular symptoms 10, 9, 8 and 7%, respectively. IMD patients diagnosed in adulthood (n = 1,426), most frequently portray neurological symptoms (65%), specifically extrapyramidal/cerebellar symptoms (57%), intellectual disability/dementia/psychiatric symptoms (41%), pyramidal tract symptoms/myelopathy (37%), peripheral neuropathy (18%), and epileptic seizures (16%). The second most frequently observed symptoms were ophthalmological (21%). In 47% of the IMD diagnosed patients, symptoms from multiple organ systems were reported. On average, adult patients are diagnosed 15 years after first presenting symptoms. Disease-related abnormalities in metabolites in plasma, urine or cerebral spinal fluid were identified in 40% of all patients whom underwent metabolic screening. In 52% the diagnosis led to identification of affected family members with the same IMD.
CONCLUSION
ES and/or GS is likely to yield an IMD diagnosis in adult patients presenting with an unexplained neurological phenotype, as well as in patients with a phenotype involving multiple organ systems. If a gene panel does not yield a conclusive diagnosis, it is worthwhile to analyze all known disease genes. Further prospective research is needed to establish the best diagnostic approach (type and sequence of metabolic and genetic test) in adult patients presenting with a wide range of symptoms, suspected of having an IMD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021295156.
PubMed: 37560457
DOI: 10.3389/fneur.2023.1206106 -
Bulletin of the World Health... May 2024To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and... (Review)
Review
OBJECTIVE
To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and economic costs comparable to those of the coronavirus disease.
METHODS
We conducted a systematic scoping review using the databases ScienceDirect, Scopus, JSTOR, PubMed® and EconLit. We included articles published in any language until 1 August 2023, and excluded grey literature and publications on epidemics. We categorized eligible studies according to the elements of a framework proposed by the World Health Organization Council on the Economy of Health for All: (i) root/structural causes; (ii) social position/foundations; (iii) infrastructure and systems; and (iv) communities, households and individuals.
FINDINGS
Of the 188 initially identified articles, we included 60 in our review. Most (53/60) were published after 2020, when academic interest had shifted towards global financing mechanisms. Most (37/60) addressed two or more of the council framework elements. The most frequently addressed element was infrastructure and systems (54/60), discussing topics such as health systems, financial markets and innovation ecosystems. The roots/structural causes were discussed in 25 articles; communities, households and individuals in 22 articles; and social positions/foundations in 11.
CONCLUSION
Our review identified three important gaps: a formal definition of pandemic preparedness and response, impeding the accurate quantification of the financing shortfall; research on the extent to which financing for pandemic preparedness and response has been targeted at the most vulnerable households; and an analysis of specific financial instruments and an evaluation of the feasibility of their implementation.
Topics: Humans; COVID-19; Pandemics; Global Health; SARS-CoV-2; Healthcare Financing; Pandemic Preparedness
PubMed: 38680465
DOI: 10.2471/BLT.23.290207 -
Frontiers in Neurology 2023Hearing can be impaired in many neurological conditions and can even represent a forme of specific disorders. Auditory function can be measured by either subjective or... (Review)
Review
Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative 'window of discovery'.
BACKGROUND
Hearing can be impaired in many neurological conditions and can even represent a forme of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear's perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function.
METHODS
A systematic review of the literature was performed, searching for papers with case-control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated.
RESULTS
Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals.
CONCLUSION
Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.
PubMed: 37662038
DOI: 10.3389/fneur.2023.1204132 -
International Journal of Molecular... Jan 2024Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic... (Meta-Analysis)
Meta-Analysis Review
Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.
Topics: Humans; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Pancreatitis, Acute Necrotizing; Procalcitonin; ROC Curve
PubMed: 38279274
DOI: 10.3390/ijms25021273 -
Journal of Nanobiotechnology Jun 2024Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials...
Manganese (Mn) is widely recognized owing to its low cost, non-toxic nature, and versatile oxidation states, leading to the emergence of various Mn-based nanomaterials with applications across diverse fields, particularly in tumor diagnosis and therapy. Systematic reviews specifically addressing the tumor diagnosis and therapy aspects of Mn-derived biomaterials are lacking. This review comprehensively explores the physicochemical characteristics and synthesis methods of Mn-derived biomaterials, emphasizing their role in tumor diagnostics, including magnetic resonance imaging, photoacoustic and photothermal imaging, ultrasound imaging, multimodal imaging, and biodetection. Moreover, the advantages of Mn-based materials in tumor treatment applications are discussed, including drug delivery, tumor microenvironment regulation, synergistic photothermal, photodynamic, and chemodynamic therapies, tumor immunotherapy, and imaging-guided therapy. The review concludes by providing insights into the current landscape and future directions for Mn-driven advancements in the field, serving as a comprehensive resource for researchers and clinicians.
Topics: Animals; Humans; Biocompatible Materials; Drug Delivery Systems; Magnetic Resonance Imaging; Manganese; Nanostructures; Neoplasms; Tumor Microenvironment
PubMed: 38879519
DOI: 10.1186/s12951-024-02629-8 -
Journal of Family Medicine and Primary... Sep 2023Coronavirus disease 2019 (COVID-19) is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both immediate and long-term adverse effects... (Review)
Review
Coronavirus disease 2019 (COVID-19) is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both immediate and long-term adverse effects arise out of this disease's aftermath. It involves various organs, which include endocrine glands, nervous system, musculoskeletal system, and other organs. The long-term outcomes of the SARS-CoV-2 infection are influenced by preexisting comorbidities. Genetic, environmental, and immunological factors contribute to the development of various autoimmune diseases, which include Graves' disease (GD). The growing mystery surrounding this virus is exacerbated by auto-inflammatory diseases, such as pediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), which raises concerns about the nature of the virus' connection to the autoimmune and auto-inflammatory sequelae. There is a need to understand the underlying mechanisms of developing GD in post-COVID-19 patients. There are limited data regarding the pathogenesis involved in post-COVID-19 GD. Our goal was to understand the various mechanisms involved in post-COVID-19 GD among patients with confirmed COVID-19 infection. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for 2020, a literature search of medical databases (PubMed, Cochrane Central Register of Controlled Trials, and Scopus) from February 2021 to February 2022 was performed by five authors. The keywords used were "Post COVID-19," "Grave's disease," "Cytokine storm," "Autoimmunity," and "Molecular mimicry." This review revealed three underlying mechanisms that resulted in post-COVID GD, which included cytokine storm, molecular mimicry, ACE2 receptor concentration, and cell-mediated immunity. The full spectrum of the effects of COVID-19 needs to be researched.
PubMed: 38024874
DOI: 10.4103/jfmpc.jfmpc_2246_22 -
High Blood Pressure & Cardiovascular... Mar 2024Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg...
Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.
Topics: Humans; Antihypertensive Agents; Blood Pressure; Drug Resistance; Drug Therapy, Combination; Hypertension; Precision Medicine; Treatment Outcome
PubMed: 38616212
DOI: 10.1007/s40292-024-00634-4 -
Phytomedicine : International Journal... Jul 2024Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically... (Review)
Review
BACKGROUND
Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically active phytochemical that acts as a nuclear factor erythroid 2-related factor 2 (Nrf2) inducer. Thus, it has been reported to have multiple protective functions including anticancer responses and protection against a toxic agent's action.
PURPOSE
The present work systematically reviewed and synthesised the protective properties of sulforaphane against a toxic agent. This review reveals the mechanism of the action of SFN in each organ or system.
METHODS
The PRISMA guideline was followed in this sequence: researched literature, organised retrieved documents, abstracted relevant information, assessed study quality and bias, synthesised data, and prepared a comprehensive report. Searches were conducted on Science Direct and PubMed using the keywords "Sulforaphane" AND ("protective effects" OR "protection against").
RESULTS
Reports showed that liver and the nervous system are the target organs on which attention was focused, and this might be due to the key role of oxidative stress in liver and neurodegenerative diseases. However, protective activities have also been demonstrated in the lungs, heart, immune system, kidneys, and endocrine system. SFN exerts its protective effects by activating the Nrf2 pathway, which enhances antioxidant defenses and reduces oxidative stress. It also suppresses inflammation by decreasing interleukin production. Moreover, SFN inhibits apoptosis by preventing caspase 3 cleavage and increasing Bcl2 levels. Overall, SFN demonstrates multifaceted mechanisms to counteract the adverse effects of toxic agents.
CONCLUSION
SFN has potential clinical applications as a chemoprotective agent. Nevertheless, more studies are necessary to set the safe doses of SFN in humans.
Topics: Isothiocyanates; Sulfoxides; Humans; Animals; Brassica; Oxidative Stress; NF-E2-Related Factor 2; Protective Agents
PubMed: 38824824
DOI: 10.1016/j.phymed.2024.155731 -
The ISME Journal Jan 2024Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing... (Review)
Review
Genome-scale metabolic models (GEMs) are valuable tools serving systems biology and metabolic engineering. However, GEMs are still an underestimated tool in informing microbial ecology. Since their first application for aerobic gammaproteobacterial methane oxidizers less than a decade ago, GEMs have substantially increased our understanding of the metabolism of methanotrophs, a microbial guild of high relevance for the natural and biotechnological mitigation of methane efflux to the atmosphere. Particularly, GEMs helped to elucidate critical metabolic and regulatory pathways of several methanotrophic strains, predicted microbial responses to environmental perturbations, and were used to model metabolic interactions in cocultures. Here, we conducted a systematic review of GEMs exploring aerobic methanotrophy, summarizing recent advances, pointing out weaknesses, and drawing out probable future uses of GEMs to improve our understanding of the ecology of methane oxidizers. We also focus on their potential to unravel causes and consequences when studying interactions of methane-oxidizing bacteria with other methanotrophs or members of microbial communities in general. This review aims to bridge the gap between applied sciences and microbial ecology research on methane oxidizers as model organisms and to provide an outlook for future studies.
Topics: Methane; Oxidation-Reduction; Aerobiosis; Metabolic Networks and Pathways; Models, Biological
PubMed: 38861460
DOI: 10.1093/ismejo/wrae102 -
European Journal of Pediatrics Oct 2023Fontan circulation is a highly abnormal circulatory state that may affect various organ systems. The effect on body composition is an important factor to assess the... (Review)
Review
Fontan circulation is a highly abnormal circulatory state that may affect various organ systems. The effect on body composition is an important factor to assess the condition of the patient. This systematic review assesses body composition and possibly related adverse outcomes in patients with a Fontan circulation, to provide an overview of current insights. Studies evaluating body composition by compartment (either fat mass or lean/muscle mass) in Fontan patients published up to April 2023 were included in this systematic review. Of 1392 potential studies, 18 studies met the inclusion criteria. In total, body composition measurements of 774 Fontan patients were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA) (n = 12), bioelectrical impedance analysis (BIA) (n = 5), computer tomography (CT) (n = 1), or magnetic resonance imaging (MRI) (n = 1). All studies reported a normal body mass index (BMI) in Fontan patients, compared to controls. Five out of nine studies reported significantly higher body fat values, and twelve out of fifteen studies reported significantly lower muscle or lean mass values in the Fontan population compared to the healthy population. Unfavorable body composition in Fontan patients was associated with decreased exercise capacity, worse cardiac function, and adverse outcomes including hospital admissions and death. Conclusions: Despite having a normal BMI, Fontan patients have an increased fat mass and decreased muscle mass or lean mass compared to the healthy population. This unfavorable body composition was associated with various adverse outcomes, including a decreased exercise capacity and worse cardiac function. What is Known: • Patients with a Fontan circulation have a decreased exercise capacity compared to healthy peers, an unfavorable body composition might be a contributor to their impaired exercise capacity. What is New: • Fontan patients are predisposed to an unfavorable body composition, characterized by increased fat mass and decreased muscle mass accompanied by a normal BMI compared to the healthy population. • Among others, unfavorable body composition was associated with decreased exercise capacity, cardiac function, and increased morbidity in patients with a Fontan circulation.
Topics: Humans; Body Composition; Adipose Tissue; Magnetic Resonance Imaging; Absorptiometry, Photon; Electric Impedance; Body Mass Index
PubMed: 37542012
DOI: 10.1007/s00431-023-05100-2