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International Journal of Rheumatic... Jan 2024Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide... (Review)
Review
Fibromyalgia (FM) is a highly prevalent chronic disease. About 4.7% of the world's population suffers from generalized pain and hypersensitivity, in addition to a wide range of physical and psychological symptoms. The etiopathogenesis of this disease is multifactorial, which makes its diagnosis and treatment challenging. Recently, the increase in the number of studies on microbiota has provided new data that can help to understand the onset and development of FM. An updated systematic review of the causes of FM has been carried out in this work. Particularly in the last decade, research has focused on the gut-brain axis, which has emerged as a crucial mechanism for microbiota-host crosstalk. In FM patients, quantitative imbalances of the intestinal microbiota (dysbiosis) and bacterial metabolites with differential relative abundance have been found, especially short-chain fatty acids and lipopolysaccharides. Furthermore, the microbiota has been found to indirectly influence host neurotransmitter mechanisms, mainly through the serotonin precursor, glutamate, and gamma-aminobutyric acid. Thus, all these mechanisms and their influence on the etiopathogenesis of FM are discussed in this review.
Topics: Humans; Gastrointestinal Microbiome; Fibromyalgia; Pain; Dysbiosis; Bacteria
PubMed: 38287551
DOI: 10.1111/1756-185X.15021 -
Pediatric Blood & Cancer Apr 2024Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life... (Review)
Review
Corticosteroids are essential to curative acute lymphoblastic leukemia (ALL) treatment, yet have significant neuropsychiatric side effects that decrease quality of life for patients and families. We conducted a scoping review, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, to describe the existing measurement tools used to evaluate neurobehavioral side effects of corticosteroids in pediatric ALL. From various databases and registers, 4047 studies were identified. Twenty-four articles met inclusion criteria. Clinical assessment was most used to evaluate these symptoms. Twelve validated measures were identified. Existing data about neuropsychiatric side effects of corticosteroids in pediatric ALL are extremely heterogeneous, creating challenges for standardized assessment and management.
Topics: Child; Humans; Quality of Life; Adrenal Cortex Hormones; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 38263506
DOI: 10.1002/pbc.30881 -
Frontiers in Pharmacology 2023Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective...
Recently, multiple preclinical studies have reported the beneficial effect of berberine in the treatment of Alzheimer's disease (AD). Nevertheless, the neuroprotective effects and possible mechanisms of berberine against AD are not universally recognized. This study aimed to conduct a systematic review and meta-analysis by integrating relevant animal studies to assess the neuroprotective effects and potential mechanisms of berberine on AD. We systematically searched PubMed, Embase, Scopus and Web of Science databases that reported the effects of berberine on AD models up to 1 February 2023. The escape latency, times of crossing platform, time spent in the target quadrant and pro-oligomerized amyloid beta 42 (Aβ) were included as primary outcomes. The secondary outcomes were the Tau-ps 204, Tau-ps 404, β-site of APP cleaving enzyme (BACE1), amyloid precursor protein (APP), acetylcholine esterase (AChE), tumor necrosis factor ⍺ (TNF-α), interleukin 1β (IL-1β), IL-6, nitric oxide (NO), glial fibrillary acidic protein (GFAP), malonaldehyde (MDA), glutathione S-transferase (GST), glutathione (GSH), glutathione peroxidase (GPx), Beclin-1 and neuronal apoptosis cells. This meta-analysis was conducted using RevMan 5.4 and STATA 15.1. The SYRCLE's risk of bias tool was used to assess the methodological quality. Twenty-two studies and 453 animals were included in the analysis. The overall results showed that berberine significantly shortened the escape latency ( < 0.00001), increased times of crossing platform ( < 0.00001) and time spent in the target quadrant ( < 0.00001), decreased Aβ deposition ( < 0.00001), Tau-ps 202 ( < 0.00001) and Tau-ps 404 ( = 0.002), and improved BACE1, APP, AChE, Beclin-1, neuronal apoptosis cells, oxidative stress and inflammation levels. Berberine may be a promising drug for the treatment of AD based on preclinical evidence (especially when the dose was 5-260 mg/kg). The potential mechanisms for these protective effects may be closely related to anti-neuroinflammation, anti-oxidative stress, modulation of autophagy, inhibition of neuronal apoptosis and protection of cholinergic system. However, these results may be limited by the quality of existing research. Larger and methodologically more rigorous preclinical research are needed to provide more convincing evidence.
PubMed: 38259291
DOI: 10.3389/fphar.2023.1287750 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Scientific Reports Jan 2024Cardiac magnetic resonance (CMR) is the gold standard for the diagnostic classification and risk stratification in most patients with cardiac disorders. The aim of the... (Meta-Analysis)
Meta-Analysis
Cardiac magnetic resonance (CMR) is the gold standard for the diagnostic classification and risk stratification in most patients with cardiac disorders. The aim of the present study was to investigate the ability of Strain-encoded MR (SENC) for the prediction of major adverse cardiovascular events (MACE). A systematic review and meta-analysis was performed according to the PRISMA Guidelines, including patients with or without cardiovascular disease and asymptomatic individuals. Myocardial strain by HARP were used as pulse sequences in 1.5 T scanners. Published literature in MEDLINE (PubMed) and Cochrane's databases were explored before February 2023 for studies assessing the clinical utility of myocardial strain by Harmonic Phase Magnetic Resonance Imaging (HARP), Strain-encoded MR (SENC) or fast-SENC. In total, 8 clinical trials (4 studies conducted in asymptomatic individuals and 4 in patients with suspected or known cardiac disease) were included in this systematic review, while 3 studies were used for our meta-analysis, based on individual patient level data. Kaplan-Meier analysis and Cox proportional hazard models were used, testing the ability of myocardial strain by HARP and SENC/fast-SENC for the prediction of MACE. Strain enabled risk stratification in asymptomatic individuals, predicting MACE and the development of incident heart failure. Of 1332 patients who underwent clinically indicated CMR, including SENC or fast-SENC acquisitions, 19 patients died, 28 experienced non-fatal infarctions, 52 underwent coronary revascularization and 86 were hospitalized due to heart failure during median 22.4 (17.2-28.5) months of follow-up. SENC/fast-SENC, predicted both all-cause mortality and MACE with high accuracy (HR = 3.0, 95% CI = 1.2-7.6, p = 0.02 and HR = 4.1, 95% CI = 3.0-5.5, respectively, p < 0.001). Using hierarchical Cox-proportional hazard regression models, SENC/fast-SENC exhibited incremental value to clinical data and conventional CMR parameters. Reduced myocardial strain predicts of all-cause mortality and cardiac outcomes in symptomatic patients with a wide range of ischemic or non-ischemic cardiac diseases, whereas in asymptomatic individuals, reduced strain was a precursor of incident heart failure.
Topics: Humans; Magnetic Resonance Imaging, Cine; Heart; Magnetic Resonance Imaging; Heart Diseases; Heart Failure; Magnetic Resonance Spectroscopy; Predictive Value of Tests; Prognosis
PubMed: 38212323
DOI: 10.1038/s41598-023-50835-5 -
Journal of Applied Toxicology : JAT Jan 2024The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A... (Review)
Review
The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.
PubMed: 38212177
DOI: 10.1002/jat.4574 -
Intensive & Critical Care Nursing Apr 2024To critically summarise the qualitative literature to understand patients' experiences of delusional memories during their Intensive Care Unit stay. (Review)
Review
OBJECTIVE
To critically summarise the qualitative literature to understand patients' experiences of delusional memories during their Intensive Care Unit stay.
RESEARCH METHODOLOGY
A systematic review of qualitative studies with meta-synthesis and meta-summary. We searched MEDLINE (via PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Web of Science to July 2022. All studies that provided qualitative insights into the subjective experience of adult patients with delusional memories in the Intensive Care Unit were selected. The Critical Assessment Skills Programme checklist was used for the quality assessment.
RESULTS
Fourteen studies were included. The 33 codes that emerged from the inductive thematic analysis were grouped into three themes: 'The sense of danger and the terrifying aspect of death' (feeling in danger, surrounded by death, persecuted by people around, and feeling unsafe), 'The presence of someone or something nearby' (perceiving the loved ones, feeling overwhelmed by scary creatures, and being neglected by those around me), and 'The reality behind the world perceived by the senses' (travelling the world, stimulating the senses, feeling peaceful, and living in a fantasy world). The most frequent code in the studies was 'Be with a family member', with an intensity of 35.7%.
CONCLUSION
The patient's experience described as delusional is considered a real event by the person experiencing it. Further research is needed to investigate the extent to which these experiences lead to poorer early and late outcomes for patients, and to test strategies to prevent this.
IMPLICATIONS FOR CLINICAL PRACTICE
A deeper understanding of the phenomenon may help healthcare professionals to recognise precursors, symptoms and consequences of delusional memories and intervene with appropriate help. One strategy would be to further humanise care and focus on family involvement and communication with patients to overcome the factual events that can potentially alter patients' quality of life.
Topics: Adult; Humans; Quality of Life; Intensive Care Units; Patients; Emotions; Family; Qualitative Research
PubMed: 38176133
DOI: 10.1016/j.iccn.2023.103617 -
Obstetrics and Gynecology Mar 2024To determine biomarkers other than CA 125 that could be used in identifying early-stage ovarian cancer.
OBJECTIVE
To determine biomarkers other than CA 125 that could be used in identifying early-stage ovarian cancer.
DATA SOURCES
Ovid MEDLINE ALL, EMBASE, Web of Science Core Collection, ScienceDirect, Clinicaltrials.gov , and CAB Direct were searched for English-language studies between January 2008 and April 2023 for the concepts of high-grade serous ovarian cancer, testing, and prevention or early diagnosis.
METHODS OF STUDY SELECTION
The 5,523 related articles were uploaded to Covidence. Screening by two independent reviewers of the article abstracts led to the identification of 245 peer-reviewed primary research articles for full-text review. Full-text review by those reviewers led to the identification of 131 peer-reviewed primary research articles used for this review.
TABULATION, INTEGRATION, AND RESULTS
Of 131 studies, only 55 reported sensitivity, specificity, or area under the curve (AUC), with 36 of the studies reporting at least one biomarker with a specificity of 80% or greater specificity or 0.9 or greater AUC.
CONCLUSION
These findings suggest that although many types of biomarkers are being tested in ovarian cancer, most have similar or worse detection rates compared with CA 125 and have the same limitations of poor detection rates in early-stage disease. However, 27.5% of articles (36/131) reported biomarkers with better sensitivity and an AUC greater than 0.9 compared with CA 125 alone and deserve further exploration.
Topics: Female; Humans; Fallopian Tubes; Ovarian Neoplasms; Biomarkers
PubMed: 38176019
DOI: 10.1097/AOG.0000000000005496 -
Cureus Nov 2023Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks... (Review)
Review
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels, severity continues to rise worldwide. This systematic review seeks to examine the prevalence of diabetes and its associated comorbid conditions, aiming to provide insights into the multifaceted impact of diabetes on a broader scale. DM exhibits a positive correlation with advancing age, and it's strongly influenced by genetic predisposition. In recent years, there has been a discernible global increase in the prevalence of type 1 diabetes (T1D), as evidenced by extensive epidemiological studies. Individuals with DM frequently have a positive familial history, and the presence of DM in both parents or solely the mother significantly amplifies genetic susceptibility. Moreover, non-genetic factors, such as acute psychological stressors, obesity, pregnancy, and smoking play a pivotal role in the development of DM. Notably, urinary tract infections (UTIs) are a common comorbidity in patients with type 2 diabetes (T2D) and all patients with T1D. T2D is prevalent, particularly among females, and its incidence rises with age. UTIs are prevalent among individuals with diabetes, particularly females, with Escherichia coli (E. coli) isolates being the primary etiological agents responsible for UTI inflammation. Insulin resistance is a common feature in both prediabetes and prehypertension, serving as a precursor to these conditions. The increasing incidence of T2D in regions with high tuberculosis (TB) prevalence emphasizes the significance of understanding DM as a substantial TB risk factor. DM is associated with a threefold elevation in TB risk and a twofold increase in unfavorable outcomes during TB treatment. Notably, the global prevalence of DM has led to a larger population of TB patients with comorbid DM than TB patients coinfected with HIV. Diabetes and sepsis contribute significantly to worldwide morbidity and mortality, with diabetic individuals experiencing more post-sepsis complications and increased mortality. The coexistence of hypertension and T2D is a common comorbidity, with hypertension incidence being twice as high among individuals with diabetes compared to those without, often linked to insulin resistance and a heightened risk of diabetes onset.
PubMed: 38146555
DOI: 10.7759/cureus.49374 -
Expert Review of Hematology 2024This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab.
METHODS
PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies.
RESULTS
The pooled complete remission (CR) rate and minimal residual disease (MRD) negative rate were 48%, 31% for blinatumomab, and 86% and 80% for CAR T-cell therapy.
CONCLUSIONS
The CAR T-cell therapy group exhibited a higher likelihood of CR rate than the blinatumomab group in every analysis regardless of adjustment subgroups. CAR T-cell therapy was associated with a significantly prolonged overall survival (OS) and relapse-free survival (RFS) compared with blinatumomab (2-year OS 55% vs 25%; 2-year RFS 40% vs 22%). CAR T-cell therapy was more effective for achieving CR and bridging to allogeneic hematopoietic stem cell transplantation (allo-SCT) than blinatumomab (2-year OS 75% vs. 57%). An emerging role for blinatumomab is as a bridging agent pre-SCT, and for patients who achieve an MRD-negative state pre-SCT, post-SCT outcomes are expected to be the same as CAR-T. For adverse effects (AEs), blinatumomab was associated with a lower rate of grade ≥3 hematological toxicity, CRS, and neurological events.
Topics: Humans; Immunotherapy, Adoptive; Hematopoietic Stem Cell Transplantation; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antibodies, Bispecific; Recurrence; Antigens, CD19
PubMed: 38135295
DOI: 10.1080/17474086.2023.2298732