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Genes Aug 2023PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as... (Review)
Review
PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome, is a recently described, rare auto-inflammatory disorder caused by specific deleterious variants in the gene (p.E250K and p.E257K). The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. Increased blood levels of MRP 8/14 and zinc distinguish this condition from other PSTPIP1-associated inflammatory diseases (PAID). The aim of this systematic review is to provide a comprehensive overview of the disease phenotype, course, treatment, and outcome based on reported cases. This systematic review adheres to the PRISMA guidelines (2020) for reporting. A literature search was performed in Embase, Medline, and Web of Science on 13 October 2022. The quality of the case reports and case series was assessed using the JBI checklists. Out of the 43 included patients with PAMI syndrome, there were 24 females and 19 males. The median age at onset was 3.9 years. The main clinical manifestations included anemia (100%), neutropenia (98%), cutaneous manifestations (74%), osteoarticular manifestations (72%), splenomegaly (70%), growth failure (57%), fever (51%), hepatomegaly (56%), and lymphadenopathy (39%). Systemic inflammation was described in all patients. Marked elevation of zinc and MRP 8/14 blood levels were observed in all tested patients. Response to treatment varied and no consistently effective therapy was identified. The most common therapeutic options were corticosteroids (N = 30), anakinra (N = 13), cyclosporine A (N = 11), canakinumab (N = 6), and anti-TNF (N = 14). Hematopoietic stem cell transplantation has been recently reported to be successful in five patients. Our review highlights the key characteristics of PAMI syndrome and the importance of considering this disease in the differential diagnosis of patients presenting with early-onset systemic inflammation and cytopenia.
Topics: Female; Male; Humans; Tumor Necrosis Factor Inhibitors; Neutropenia; Diagnosis, Differential; Cytoskeletal Proteins; Adaptor Proteins, Signal Transducing
PubMed: 37628706
DOI: 10.3390/genes14081655 -
Clinical Infectious Diseases : An... Aug 2023In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma...
Risk of Hepatocellular Carcinoma After Spontaneous Clearance of Hepatitis C Virus and in Noncirrhosis Chronic Hepatitis C Patients With Sustained Virological Response: A Systematic Review.
In a hepatitis C virus (HCV)-controlled human infection model (CHIM), healthy volunteers are inoculated with HCV and then treated. Residual hepatocellular carcinoma (HCC) risk after viral clearance is an important consideration when evaluating the CHIM. We estimate HCC risk in spontaneously cleared HCV and in noncirrhosis after sustained virological response (SVR) to HCV treatment in a systematic review and using data from 3 cohorts: German anti-D, Taiwan, and US Veterans Affairs (VA). For noncirrhosis SVR, the overall HCC rate is 0.33 per 100 patient-years in meta-analysis. HCC rates for the German, Taiwan, and US Veterans Affairs cohorts are 0, 0.14, and 0.02 per 100 patient-years, respectively. Past hepatitis B virus exposure was not accounted for in the Taiwan cohort, while VA patients were likely tested based on liver disease/risk factors, which may confound HCC outcomes. The German cohort with no HCC after 44 years is most comparable to the CHIM participants. Although it is difficult to precisely estimate HCC risk from an HCV CHIM, the data suggest the risk to be very low or negligible.
Topics: Humans; Antiviral Agents; Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Liver Neoplasms; Sustained Virologic Response
PubMed: 37579210
DOI: 10.1093/cid/ciad380 -
International Journal of Molecular... Mar 2024Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn's disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual's drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Biological Products; Biomarkers
PubMed: 38612528
DOI: 10.3390/ijms25073717 -
Cureus Dec 2023This study aims to investigate and address the issue of emergency department (ED) overcrowding, a significant problem worldwide. The study seeks to understand the... (Review)
Review
This study aims to investigate and address the issue of emergency department (ED) overcrowding, a significant problem worldwide. The study seeks to understand the impacts of ED overcrowding on emergency medical healthcare services and patient outcomes. This systematic review follows the PRISMA flow diagram and the guidelines of the Cochrane Handbook. We systematically reviewed the causes and solutions of emergency department overcrowding. We went through Google Scholar, the National Center for Biotechnology Information, the British Medical Journal, Science Direct, Ovid, Cochrane, the Saudi Journal of Emergency Medicine, Medline, and PubMed as databases. Our criteria were articles done in Saudi Arabia from 2012 to 2022. One hundred and ninety-six (196) research papers were extracted; only 28 articles met our paper inclusion-exclusion criteria. The result of these papers regarding causes, consequences, and solutions was that non-urgent and returned visits lacked knowledge of PHC, triad, and telemedicine services. Prolonged LOS is due to slow bed turnover, laboratory and consultation time, and physical response to the final decision resulting in burnout staff, wrong diagnoses, and management plans. The crowding issues can be resolved by awareness, PHC access, triad systems, and technological and telemedicine services. High demand for emergency treatment should not be a hindrance to quality treatment. Physical, technological, and strategic measures should be put in place to fight the crowding problem in EDs in Saudi Arabia, as it may cause adverse effects such as transmission of diseases and death of patients.
PubMed: 38229791
DOI: 10.7759/cureus.50669 -
Medicine Dec 2023Chronic prostatitis (CP) is a common condition that affects many individuals. Previous clinical trials have explored the use of moxibustion as a potential treatment for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic prostatitis (CP) is a common condition that affects many individuals. Previous clinical trials have explored the use of moxibustion as a potential treatment for CP. However, the evidence on the effectiveness of moxibustion for CP remains limited. Therefore, this study aimed to comprehensively assess the effects of moxibustion for CP.
METHODS
In order to gather relevant and up-to-date information, we conducted a systematic literature search of databases including Cochrane Library, PUBMED, EMBASE, CNKI, and Wangfang from inception until June 30, 2023. Only randomized clinical trials (RCTs) that investigated the use of moxibustion for CP were included in this study. The primary outcomes of interest were the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores and the overall response rate. To evaluate the quality of the included studies, we used the Cochrane risk-of-bias tool.
RESULTS
After analyzing the data from 8 RCTs involving a total of 664 patients, we found significant differences in NIH-CPSI scores between moxibustion and other treatment modalities. Specifically, when compared with herbal medicine, moxibustion was associated with a mean difference (MD) of -1.78 in NIH-CPSI scores (95% confidence interval [CI] [-2.78, -0.78], P < .001), and when compared with western medicine, moxibustion was associated with a MD of -5.24 in NIH-CPSI scores (95% CI [-7.80, -2.67], P < .08). In terms of the overall response rate, moxibustion was found to be superior to herbal medicine, with a MD of 2.36 (95% [19, 4.67], P = .01). Additionally, when moxibustion was combined with herbal medicine, it yielded a higher overall response rate with a MD of 4.07 (95% CI [1.54, 10.74], P = .005) compared to herbal medicine alone. Moxibustion also outperformed western medicine in terms of the overall response rate, with a MD of 4.56 (95% CI [2.24, 9.26], P < .001).
CONCLUSION
Based on the findings of this study, moxibustion appears to be a potentially efficacious treatment for CP. The results suggest that moxibustion can improve NIH-CPSI scores and overall response rate in patients with CP. However, further high-quality studies are needed to validate these results and establish the long-term effects of moxibustion as a treatment for CP.
Topics: Male; Humans; Moxibustion; Prostatitis; Chronic Disease; Acupuncture Therapy; Plant Extracts; Randomized Controlled Trials as Topic
PubMed: 38115243
DOI: 10.1097/MD.0000000000036742 -
Diseases (Basel, Switzerland) Feb 2024About half of the world's population is at risk of dengue infection. Epidemics of dengue fever have caused an increased risk of morbidity and mortality in recent years,... (Review)
Review
About half of the world's population is at risk of dengue infection. Epidemics of dengue fever have caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines and searching multiple databases, including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0-17 years old). Quality assessment was analyzed using the Cochrane Collaboration criteria, while data synthesis was conducted using thematic analysis and meta-analysis. Among the 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. The CYD-TDV (Dengvaxia) and Tekade (TAK-003) vaccines showed strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines showed promising efficacy and immune response, particularly against severe manifestations.
PubMed: 38391779
DOI: 10.3390/diseases12020032 -
BMC Public Health Sep 2023Knowledge surrounding the association between exposure to pesticides and hypothyroidism is inconsistent and controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Knowledge surrounding the association between exposure to pesticides and hypothyroidism is inconsistent and controversial.
METHODS
The aim of present study was, therefore, to review scientific evidence systematically and conduct a meta-analysis into the contribution of exposure to pesticides to hypothyroidism. PubMed, Scopus, Web of Science, and Google Scholar were searched. The findings are presented as OR, HR, PR, IRR, and 95% confidence interval (95%CI). A fixed-effect model using the inverse-variance method and random-effects inverse-variance model with DerSimonian-Laird method were used for estimating the pooled estimates. Cochran Q and I tests were used to confirm the heterogeneity of selected studies.
RESULTS
Twelve studies were included in the systematic review, and 9 studies in the meta-analysis. Epidemiological evidence suggested that exposure to insecticides including organochlorines, organophosphates, and pyrethroids increased risk of hypothyroidism (adjusted odds ratio (aOR) = 1.23, 95%CI = 1.14, 1.33 for organochlorines, aOR = 1.12, 95%CI = 1.07, 1.17 for organophosphates, aOR = 1.15, 95%CI = 1.03, 1.28 for pyrethroids). Exposure to herbicides also increased risk of hypothyroidism (aOR = 1.06, 95%CI = 1.02, 1.10). However, exposure to fungicides and fumigants was not found to be associated with hypothyroidism.
CONCLUSION
To increase current knowledge and confirm evidence to date future research needs to center on large-scale longitudinal epidemiological and biological studies, examination of dose-response relationships, the controlling of relevant confounding variables, using standardized and high sensitivity tools, and investigating the effects of environmental exposure.
Topics: Humans; Pesticides; Insecticides; Environmental Exposure; Hypothyroidism; Pyrethrins
PubMed: 37752464
DOI: 10.1186/s12889-023-16721-5 -
Journal of Clinical Medicine Oct 2023This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active... (Review)
Review
This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes.
PubMed: 37959208
DOI: 10.3390/jcm12216742 -
La Clinica Terapeutica 2023Nutrigenomics - the study of the interactions between genetics and nutrition - has emerged as a pivotal field in personalized nutrition. Among various genetic... (Review)
Review
BACKGROUND
Nutrigenomics - the study of the interactions between genetics and nutrition - has emerged as a pivotal field in personalized nutrition. Among various genetic variations, single-nucleotide polymorphisms (SNPs) have been extensively studied for their probable relationship with metabolic traits.
METHODS
Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources.
RESULTS
SNPs have demonstrated a significant influence on lipid metabolism, by impacting genes that encode for enzymes involved in lipid synthesis, transport, and storage. Furthermore, they have the ability to affect enzymes in glycolysis and insulin signaling pathways: in a way, they can influence the risk of type 2 diabetes. Thanks to recent advances in genotyping technologies, we now know numerous SNPs linked to lipid and carbohydrate metabolism. The large-scale studies on this topic have unveiled the potential of personalized dietary recommendations based on an individual's genetic makeup. Personalized nutritional interventions hold promise to mitigate the risk of various chronic diseases; however, translating these scientific insights into actionable dietary guidelines is still challenging.
CONCLUSIONS
As the field of nutrigenomics continues to evolve, collaborations between geneticists, nutritionists, and healthcare providers are essential to harness the power of genetic information for improving metabolic health. By unraveling the genetic basis of metabolic responses to diet, this field holds the potential to revolutionize how we approach dietary recommendations and preventive healthcare practices.
Topics: Humans; Nutrigenomics; Polymorphism, Single Nucleotide; Diabetes Mellitus, Type 2; Diet; Lipids; Carbohydrate Metabolism
PubMed: 37994765
DOI: 10.7417/CT.2023.2488 -
EClinicalMedicine Mar 2024Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on...
BACKGROUND
Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain.
METHODS
In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148).
FINDINGS
This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years.
INTERPRETATION
BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD.
FUNDING
Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.
PubMed: 38374967
DOI: 10.1016/j.eclinm.2024.102482