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Frontiers in Immunology 2023Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical condition characterized by sustained but ineffective immune system activation, leading to severe and systemic... (Review)
Review
Hemophagocytic Lymphohistiocytosis (HLH) is a rare clinical condition characterized by sustained but ineffective immune system activation, leading to severe and systemic hyperinflammation. It may occur as a genetic or sporadic condition, often triggered by an infection. The multifaceted pathogenesis results in a wide range of non-specific signs and symptoms, hampering early recognition. Despite a great improvement in terms of survival in the last decades, a considerable proportion of patients with HLH still die from progressive disease. Thus, prompt diagnosis and treatment are crucial for survival. Faced with the complexity and the heterogeneity of syndrome, expert consultation is recommended to correctly interpret clinical, functional and genetic findings and address therapeutic decisions. Cytofluorimetric and genetic analysis should be performed in reference laboratories. Genetic analysis is mandatory to confirm familial hemophagocytic lymphohistiocytosis (FHL) and Next Generation Sequencing is increasingly adopted to extend the spectrum of genetic predisposition to HLH, though its results should be critically discussed with specialists. In this review, we critically revise the reported laboratory tools for the diagnosis of HLH, in order to outline a comprehensive and widely available workup that allows to reduce the time between the clinical suspicion of HLH and its final diagnosis.
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Genetic Predisposition to Disease
PubMed: 37426667
DOI: 10.3389/fimmu.2023.1210041 -
JAMA Oncology Oct 2023Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with...
IMPORTANCE
Immune checkpoint inhibitors (ICIs) are increasingly used in patients with advanced hepatocellular carcinoma (HCC). However, data on ICI therapy in patients with advanced HCC and impaired liver function are scarce.
OBJECTIVE
To conduct a systematic review and meta-analysis to determine the efficacy and safety of ICI treatment for advanced HCC with Child-Pugh B liver function.
DATA SOURCES
PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant studies from inception through June 15, 2022.
STUDY SELECTION
Randomized clinical trials, cohort studies, or single-group studies that investigated the efficacy or safety of ICI therapy for Child-Pugh B advanced HCC were included.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 > 50%); otherwise, a fixed-effect model was used.
MAIN OUTCOMES AND MEASURES
The objective response rate (ORR) and overall survival (OS) were considered to be the primary efficacy outcomes of ICI treatment for Child-Pugh B advanced HCC, and the incidence of treatment-related adverse events (trAEs) was set as the primary measure for the safety outcome.
RESULTS
A total of 22 studies including 699 patients with Child-Pugh B and 2114 with Child-Pugh A advanced HCC comprised the analytic sample (median age range, 53-73 years). Upon pooled analysis, patients treated with ICIs in the Child-Pugh B group had an ORR of 14% (95% CI, 11%-17%) and disease control rate (DCR) of 46% (95% CI, 36%-56%), with a median OS of 5.49 (95% CI, 3.57-7.42) months and median progression-free survival of 2.68 (95% CI, 1.85-3.52) months. The rate of any grade trAEs in the Child-Pugh B group was 40% (95% CI, 34%-47%) and of grade 3 or higher trAEs was 12% (95% CI, 6%-23%). Compared with the Child-Pugh A group, the ORR (odds ratio, 0.59; 95% CI, 0.43-0.81; P < .001) and DCR (odds ratio, 0.64; 95% CI, 0.50-0.81; P < .001) were lower in the Child-Pugh B group. Child-Pugh B was independently associated with worse OS in patients with advanced HCC treated with ICIs (hazard ratio, 2.72 [95% CI, 2.34-3.16]; adjusted hazard ratio, 2.33 [95% CI, 1.81-2.99]). However, ICIs were not associated with increased trAEs in the Child-Pugh B group.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that although the safety of ICI treatment was comparable between patients with HCC with vs without advanced liver disease and the treatment resulted in a significant number of radiologic responses, survival outcomes are still inferior in patients with worse liver function. More study is needed to determine the effectiveness of ICI treatment in this population.
PubMed: 37615958
DOI: 10.1001/jamaoncol.2023.3284 -
Jornal de Pediatria 2024Malnutrition is characterized by situations of undernutrition and obesity resulting from the lack of micronutrients with the greatest impact on children. The objective... (Review)
Review
OBJECTIVE
Malnutrition is characterized by situations of undernutrition and obesity resulting from the lack of micronutrients with the greatest impact on children. The objective of this review was to highlight inadequate food consumption, food security, and nutritional inadequacy leading to hidden hunger and the prevention and treatment of the main micronutrient deficiencies in Brazil.
DATA SOURCE
Literature review carried out through a bibliographic survey in PubMed (National Library of Medicine, United States), Lilacs (Latin American and Caribbean Literature in Health Sciences), and SciELO (Scientific Electronic Library Online) databases. The search used the terms Occult hunger, (hidden hunger), and Child, in articles published between 2013 and 2023 in Portuguese, English and Spanish. The search was performed on 06/25/2023.
DATA SYNTHESIS
The lack of micronutrients can occur insidiously and without clinical manifestations, being called hidden hunger. The prevention of nutritional deficiencies is part of the recommended actions in childcare, with healthy eating. Studies were cited related to macro and micronutrient intake deficiencies, both national and international, and strategies to improve micronutrient intake, including routine supplementation of iron, and vitamins D and A. The diagnosis, prevention, and treatment of the main deficiencies in Brazil (iron, vitamin A, vitamin D, zinc), currently adopted, concluded the topic.
CONCLUSION
Zero hunger and zero obesity must be part of the same policy, together with a nutritional education program.
Topics: Child; Humans; Hunger; Malnutrition; Vitamin A; Micronutrients; Obesity; Iron
PubMed: 37918810
DOI: 10.1016/j.jped.2023.08.009 -
Human Vaccines & Immunotherapeutics Aug 2023Treatment of metastatic renal cell carcinoma (mRCC) has radically changed, switching from interferon alfa (IFN-α) and high-dose interleukin-2 (HD IL-2) to new targeted... (Review)
Review
Treatment of metastatic renal cell carcinoma (mRCC) has radically changed, switching from interferon alfa (IFN-α) and high-dose interleukin-2 (HD IL-2) to new targeted therapies directed against tumoral neoangiogenesis, the mammalian target of the rapamycin (mTOR) pathway and immune checkpoints. Of note, the inhibition of immune checkpoints restores antitumor immune response, therefore promoting immune-mediated elimination of neoplastic cells. The best example of this targeted treatment is represented by PD-1/PD-L1 inhibition that has become the standard of care in mRCC treatment and has improved mRCC patients' prognoses after failure of other targeted therapies. In this manuscript, we review the main therapeutic protocols adopted for mRCC, based on the use of immune checkpoint inhibitors (ICIs) alone or combined with other drugs.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Interferon-alpha
PubMed: 37395601
DOI: 10.1080/21645515.2023.2225386 -
Scientific Reports Jul 2023Daytime napping, a habit widely adopted globally, has an unclear association with obesity. In this study, we executed a meta-analysis to explore the relationship between... (Meta-Analysis)
Meta-Analysis
Daytime napping, a habit widely adopted globally, has an unclear association with obesity. In this study, we executed a meta-analysis to explore the relationship between daytime napping and obesity. We conducted a comprehensive search of the PubMed, Embase, Cochrane Library, Scopus, PsycINFO, and Web of Science databases for pertinent articles published up to April 2023. Random-effects models were utilized to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and we assessed the heterogeneity of the included studies using the I statistic. To explore potential sources of heterogeneity, subgroup analyses were performed. The methodological quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and funnel plots were employed to detect any publication bias. Sensitivity analyses were conducted by sequentially omitting each study. We conducted a meta-analysis of twelve studies that included one each from the UK and Spain, five from the USA, and five from China, totalling 170,134 participants, to probe the association between napping and obesity. The pooled analysis suggested a higher risk of obesity in individuals who nap (OR: 1.22 [1.10-1.35], p < 0.001, I = 87%) compared to non-nappers. The meta-analysis results revealed variations in the summary ORs for studies conducted in China, Spain, the USA, and the UK. The ORs for China, Spain, the USA, and the UK were 1.05 (95% CI 0.90-1.23), 9.36 (95% CI 4.74-18.45), 1.27 (95% CI 1.10-1.47), and 1.39 (95% CI 1.32-1.47), respectively. A subgroup analysis based on age within the American population disclosed that napping in both adults and children heightened obesity incidence. A subgroup analysis based on nap duration found a significant rise in obesity occurrence when nap duration exceeded one hour, but no clear relationship emerged when nap duration was less than 1 h. In a subgroup analysis based on the definition of obesity, napping did not demonstrate a significant relationship with obesity when diagnostic criteria set obesity at a BMI of 25 or above. However, when the criteria were set at a BMI of 28 or 30 or more, napping significantly increased obesity risk. Our meta-analysis indicates a positive association between daytime napping and the risk of obesity. However, given the limited number of included studies, potential confounding factors might not have been fully addressed. Future well-designed prospective studies are required to further investigate this relationship. Large-scale studies are necessary to confirm our findings and elucidate the underlying mechanisms that drive these associations and causation.
Topics: Adult; Child; Humans; Sleep; Obesity; Prospective Studies; Incidence; Habits
PubMed: 37495671
DOI: 10.1038/s41598-023-37883-7 -
Brain : a Journal of Neurology Dec 2023Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific...
Neuromuscular diseases (NMDs) affect ∼15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management. We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions. We recruited 6001 participants in the first 43 months. Initial genetic analyses 'solved' or 'possibly solved' ∼56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a ∼59% 'solved' and ∼13% 'possibly solved' outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research. In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally.
Topics: Humans; Peripheral Nervous System Diseases; Neuromuscular Diseases; Muscular Dystrophies; Muscular Dystrophies, Limb-Girdle; DNA
PubMed: 37516995
DOI: 10.1093/brain/awad254 -
Nutrients Aug 2023Nutritional intervention is worldwide recognized as a first step treatment for subjects with increased cardiovascular risk and it is of utmost importance especially for... (Review)
Review
Nutritional intervention is worldwide recognized as a first step treatment for subjects with increased cardiovascular risk and it is of utmost importance especially for children and adolescents. Currently scientific evidence supports the role of dietary patterns instead of simple single nutrients or foods in cardiovascular risk prevention. Indeed, the American Heart Association dietary guidelines have expanded beyond nutrients to dietary pattern, that comprise not only single food items but also behavioral or cultural habits of specific populations. The aim of our narrative review is to analyze the most frequently adopted dietary patterns in children and adolescents and to evaluate their effect on cardiovascular risk factors and in cardiovascular risk prevention. Literature review showed that children cannot be considered as little adults: nutritional intervention must always grant adequate growth and neurodevelopment before reaching the proposed goals, therefore dietary patterns considered heart-healthy for adult subjects might not be suitable for pediatric patients. Mediterranean diet, DASH diet, Nordic diet and some plant-based diets seem to be the most promising dietary patterns in terms of cardiovascular health in the developmental age, even if further studies are needed to better standardize and analyze their effect on growing up individuals.
Topics: Adolescent; Adult; Humans; Child; Cardiovascular Diseases; Risk Factors; Food; Diet, Mediterranean; Heart Disease Risk Factors
PubMed: 37630854
DOI: 10.3390/nu15163664