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The Spine Journal : Official Journal of... Jun 2024Copper deficiency myelopathy (CDM) is a rare disease that can present with spastic quadriparesis and sensory ataxia. As a result, it can precisely mimic cervical... (Review)
Review
BACKGROUND AND CONTEXT
Copper deficiency myelopathy (CDM) is a rare disease that can present with spastic quadriparesis and sensory ataxia. As a result, it can precisely mimic cervical spondylitic myelopathy (CSM). Copper deficiency may be seen following gastric bypass surgery, malabsorption syndromes such as celiac disease, and with excessive exogenous zinc intake. We present a systematic review of the literature for CDM and an illustrative case .
PURPOSE
Provide a systematic review of CDM to highlight the importance of recognizing the consideration of CDM in patients presenting to a spine surgeon with myelopathy that progress despite adequate surgical decompression, or myelopathy concomitant with cytopenia, thus requiring further workup.
STUDY DESIGN/SETTING
Retrospective medical record review and systematic review of the literature PATIENT SAMPLE: PubMed and Ovid-Embase database search was conducted in July 2022 OUTCOME MEASURES: Self-reported measures include PRISMA flow diagram for retrospective review; Physiological measures include retrospective review of MRI imaging of cervical spine; alternate demographic and laboratory value data extracted via literature review METHODS: A PubMed and Ovid-Embase database search was conducted in July 2022 searching for "copper deficiency myelopathy [MeSH]" from 2000 to 2022 via PRISMA guidelines. Following title and abstract review, the following data was extracted from full text: age, sex, etiology, hematological values upon presentation (mean corpuscular volume, white blood count, platelet count, and hemoglobin level), metal serum studies (serum copper, ceruloplasmin, and zinc), 24-hour collection of copper and zinc, and distinct radiographic findings on MRI.
RESULTS
A total of 116 studies were included in this review which contained 198 cases of copper deficiency myelopathy. The mean age was 53.57 ± 14.14 years, with the majority being females (63.8%). The most common etiology was prior gastric surgery (n=55, 36.2 %) followed by excessive zinc consumption from the use of zinc denture cream (n=39, 19.9%)The mean serum copper was 15.67 ± 17.84 (normal=80.0-155.0) mcg/dL and mean ceruloplasmin was 6.43 ± 5.25 (normal=16-45) mg/dL. In spite of appropriate treatment with copper supplementation, only 47 cases (24%) reported improvement in neurological status, and only 10 (5.1%) recovered to baseline. A hyperintense T2 signal abnormality resembling an inverted "v" in the dorsal columns was the most common radiographic abnormality.
CONCLUSION
Pertinent risk factors for copper deficiency myelopathy include prior upper gastrointestinal surgery, zinc excess, and malabsorption. Characteristic laboratory and imaging findings include cytopenia, low serum copper and ceruloplasmin, and distinct inverted "v" T2 signal hyperintensity in the dorsal columns. The neurologic deterioration with copper deficiency will progress in spite of decompressive surgery, and can be devastating and irreversible even with copper supplementation, reinforcing the importance of early detection. We thus recommend patients with myelopathy presenting with a history of gastric bypass, malabsorption syndromes, excessive zinc exposure, cytopenia, or imaging resembling an inverted "v" shaped hyperintense T2 MRI signal in the dorsal columns, should first undergo blood tests for copper, ceruloplasmin, and B12 levels prior to surgical consideration.
PubMed: 38909910
DOI: 10.1016/j.spinee.2024.06.018 -
Veterinary Microbiology Jun 2024Avian reovirus (ARV) is a significant pathogen that causes various clinical diseases in chickens, including viral arthritis, chronic respiratory diseases, retarded...
Avian reovirus (ARV) is a significant pathogen that causes various clinical diseases in chickens, including viral arthritis, chronic respiratory diseases, retarded growth, and malabsorption syndrome. These conditions result in substantial economic losses for the global poultry industry. MicroRNAs (miRNAs), a type of small noncoding RNAs that regulate gene expression post transcriptionally by silencing or degrading their RNA targets, play crucial roles in response to pathogenic infections. In this study, transfection of DF-1 cells with gga-miR-200a-3p, an upregulated miRNA observed in ARV-infected cells, significantly suppressed ARV-induced apoptosis by directly targeting GRB2 and impeded ARV replication. Conversely, knockdown of endogenous gga-miR-200a-3p in DF-1 cells using a specific miRNA inhibitor enhanced ARV-induced apoptosis and promoted GRB2 expression, thereby facilitating viral growth within cells. Consistently, inhibition of GRB2 activity through siRNA-mediated knockdown reduced viral titers. Therefore, gga-miR-200a-3p plays a vital antiviral role in the host response to ARV infection by suppressing apoptosis via direct targeting of GRB2 protein. This information enhances our understanding of the mechanisms by which host cells combat against ARV infection through self-encoded small RNA molecules and expands our knowledge regarding the involvement of microRNAs in the host response to pathogenic infections.
PubMed: 38909417
DOI: 10.1016/j.vetmic.2024.110149 -
Medicine Jun 2024The link between celiac disease (CeD) and thyroid dysfunction has been investigated. However, it is uncertain if CeD is causally linked to thyroid dysfunction. A...
The link between celiac disease (CeD) and thyroid dysfunction has been investigated. However, it is uncertain if CeD is causally linked to thyroid dysfunction. A 2-sample Mendelian randomization study was conducted to ascertain the causal connection between CeD and thyroid dysfunction. Using data from the FinnGen Consortium, a 2-sample Mendelian randomization study was conducted to look at the connection between thyroid dysfunction and CeD. Another replication of the data from the UK Biobank was subsequently performed to confirm our findings. Furthermore, a sequence of sensitivity analyses was performed. The inverse variance weighting technique demonstrates that genetically determined CeD is substantially linked with hypothyroidism, thyrotoxicosis, Graves' disease, and free thyroxine. However, no significant associations were found between CeD and thyroid-stimulating hormone or thyroiditis. Moreover, we achieve the same results in duplicate datasets, which increases the reliability of our findings. This study suggests that CeD and thyroid dysfunction are linked, and it gives theoretical support and new ways of thinking about how to diagnose and treat both conditions.
Topics: Humans; Mendelian Randomization Analysis; Celiac Disease; Thyroid Diseases; Hypothyroidism; Thyrotropin
PubMed: 38905357
DOI: 10.1097/MD.0000000000038474 -
Zhonghua Yi Xue Za Zhi Jun 2024The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia...
The clinical manifestations, biochemical and metabolic data, genetic variations and treatment data of children with MTHFR gene variant induced hyperhomocysteinemia admitted to Hangzhou Children's Hospital and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from November 2015 to September 2021 were analysed retrospectively. A total of 15 pediatric patients were included, including 10 males and 5 females, with onset ages ranging from 6 days to 18 years old and confirmed ages ranging from 40 days to 18 years old. One confirmed case was detected through neonatal screening, and the remaining 14 cases were all diagnosed through genetic diagnosis after onset. The main clinical manifestations were feeding difficulties, hypotonia, epilepsy, developmental delay. All patients had elevated levels of blood homocysteine, with blood homocysteine levels before and after treatment being (151.46±57.44) μmol/L and (69.96±32.88) μmol/L, significantly decreased after treatment compared with before treatment, with a statistically significant difference (<0.001). The blood methionine level before the treatment was 9.40 (6.20, 11.96) μmol/L, normal or slightly decreased compared to the reference range. The methionine level returned to normal after treatment. A total of 19 MTHFR gene variants were detected, with 6 being unreported variants and 13 being known variants. c.1316C>T (p.L439P) was the most common variant(16.6%,5/30). All the patients had varied neurological damages, with 7 patients improved after metabolic therapy by carnitine and folinic acid, 8 patients experiencing developmental delay, and 1 patient experiencing frequent epilepsy. The clinical manifestations of MTHFR gene variation-related hyperhomocysteinemia are complex and variable. Early-onset and homozygous variants often have a poor prognosis. Blood homocysteine, blood amino acid analysis, serum total homocysteine assay and gene testing are helpful for early diagnosis.
Topics: Humans; Methylenetetrahydrofolate Reductase (NADPH2); Hyperhomocysteinemia; Male; Female; Child; Child, Preschool; Adolescent; Infant; Retrospective Studies; Homocysteine; Infant, Newborn; Mutation; Methionine
PubMed: 38901983
DOI: 10.3760/cma.j.cn112137-20240125-00192 -
Clinical Nutrition ESPEN Aug 2024Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment....
Plasma metabolomics changes comparing daytime to overnight infusions of home parenteral nutrition in adult patients with short bowel syndrome: Secondary analysis of a clinical trial.
BACKGROUND
Home parenteral nutrition (HPN) is often cycled nocturnally and is expected to result in glucose intolerance and sleep disruption partly due to circadian misalignment. This study aimed to define the metabolic response when HPN is cycled during the daytime compared to overnight.
METHODS
This secondary analysis leveraged samples from a clinical trial in adults with short bowel syndrome consuming HPN (ClinicalTrials.gov: NCT04743960). Enrolled patients received 1 week of HPN overnight followed by 1 week of HPN during the daytime. Fasting blood samples were collected following each study period and global metabolic profiles were examined from plasma samples. Differential metabolite abundance was determined from normalized and scaled data using adjusted Linear Models for MicroArray Data models followed by pathway enrichment analysis.
RESULTS
Nine patients (mean age, 52.6 years; 78% female; mean BMI 20.7 kg/m) provided samples. Among 622 identified metabolites, changes were observed in 36 metabolites at P < 0.05 with higher abundance of fatty acids, long-chain and polyunsaturated fatty acids (Dihomo-gamma-linolenic acid, arachidonate (20:4n6), docosahexaenoate (DHA; 22:6n3)) and glycerolipids with daytime infusions. Enrichment analysis identified changes in pathways related to the biosynthesis of unsaturated fatty acids, d-arginine, and d-ornithine metabolism, and linoleic acid metabolism (P<0.05).
CONCLUSION
Daytime infusions of HPN may result in changes in circulating lipids and amino acid composing metabolic pathways previously implicated in circadian rhythms. As this is the first untargeted metabolomics study of HPN, larger studies are needed.
Topics: Humans; Female; Male; Middle Aged; Short Bowel Syndrome; Parenteral Nutrition, Home; Metabolomics; Adult; Circadian Rhythm
PubMed: 38901946
DOI: 10.1016/j.clnesp.2024.04.025 -
Arquivos de Gastroenterologia 2024Low bone mass density (BMD) is an extraintestinal finding in celiac disease (CD). This may result in bone fractures leading to loss in quality of life.
BACKGROUND
Low bone mass density (BMD) is an extraintestinal finding in celiac disease (CD). This may result in bone fractures leading to loss in quality of life.
OBJECTIVE
To assess BMD in male CD patients at diagnosis according to the patient's age.
METHODS
Descriptive retrospective carried out during the period between 2013 and 2023 in a single office that studied dual-energy X-ray absorptiometry (DXA) results in 28 male patients with a recent diagnosis of CD, divided into three groups: group 1 (age up to 18 years); group 2 (from 19 to 49 years of age) and group 3 (over 50 years of age). Were studied demographic and anthropometric parameters, time delay between symptoms onset and CD diagnosis and fracture occurrence.
RESULTS
Celiac patients studied had median age 36.0 years (IQR=16.5-50.7). Among them, 39.3% had osteopenia and 14.3% had osteoporosis. Only 36% of the sample had normal DXA values (group 1 with 37.5%; group 2 with 46% and group 3 with 14.2%). No pathological fracture was observed in this sample. CD diagnosis delay observed had median 1.0 year (IQR=1.0-4.7). When the number of individuals with normal and abnormal DXA results were compared, there was no difference in body mass index, time of diagnosis delay or Marsh classification (P=0.18).
CONCLUSION
Male patients at the time of CD diagnosis showed a high prevalence of low BMD, which was particularly evident in individuals over 50 years of age.
Topics: Humans; Male; Celiac Disease; Adult; Middle Aged; Retrospective Studies; Absorptiometry, Photon; Bone Density; Osteoporosis; Young Adult; Adolescent; Bone Diseases, Metabolic; Brazil; Age Factors; Aged
PubMed: 38896576
DOI: 10.1590/S0004-2803.24612024-005 -
Patient Preference and Adherence 2024Understanding the quality of life and the factors that influence it for patients with short bowel syndrome (SBS) and their caregivers is of utmost importance in order to... (Review)
Review
PURPOSE
Understanding the quality of life and the factors that influence it for patients with short bowel syndrome (SBS) and their caregivers is of utmost importance in order to enhance their well-being. Therefore, This study aimed to provide a comprehensive understanding of the impact of SBS on patients and their caregivers, as well as its associated factors, by synthesizing the available evidence.
METHODS
A systematic review of the literature was done using PubMed, Embase databases, CNKI, and ISPOR conference papers. Included articles were manually searched to identify any other relevant studies. Quality was assessed using appropriate Joanna Briggs Institute critical appraisal tools.
RESULTS
This review included 16 studies, comprising 15 observational studies and 1 randomized controlled trial. The findings revealed that the QoL of patients with SBS was lower than that of the general population regarding physical functioning and psychological domain. Meanwhile, caregivers experienced challenges in maintaining their QoL. The QoL of SBS patients was found to be influenced by various factors such as treatment, age, sex, stoma, and small intestine length. Among them, the treatment is the most noteworthy factor that can be effectively improved through external interventions.
CONCLUSION
While numerous studies have provided insights into the compromised QoL experienced by individuals with SBS and their caregivers, there remains a scarcity of large-sample quantitative investigations examining the determinants of QoL. The existing body of literature on caregivers is also notably deficient.
PubMed: 38895637
DOI: 10.2147/PPA.S443026 -
Nutrients Jun 2024Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants... (Review)
Review
Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD.
Topics: Celiac Disease; Humans; Vitamin D; Gastrointestinal Microbiome; Vitamin D Deficiency; Thyroiditis, Autoimmune; Dysbiosis; Dietary Supplements; Autoimmune Diseases; Thyroid Diseases
PubMed: 38892695
DOI: 10.3390/nu16111762 -
Nutrients May 2024Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture....
Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally advised to continue on a gluten-containing diet (GCD), but long-term risks of this approach have never been explored. In the present study, we aimed to investigate nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children on a GCD. We compared children's parameters of growth, nutritional status, and autoimmunity between the time of diagnosis and on the occasion of their last medical check, after a long-term gluten-containing diet. Altogether, we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35-15.3 years). During follow-up, although patients did not reduce their amount of daily gluten intake, their anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most parameters analysed had not changed during follow-up (height centile, ferritin, albumin, cholesterol, calcium, alkaline phosphatase, parathormone, and vitamin D) or even improved significantly (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia, and HbA1C, < 0.05), always remaining within the limit of normality. Equally, autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from analysis patients who had stopped producing anti-TG2 and those with a follow-up time < 3 years. Our pilot study has provided reassuring results regarding the maintenance of a gluten-containing diet in asymptomatic PCD children, even when long-term follow-up was considered.
Topics: Humans; Celiac Disease; Child; Male; Female; Child, Preschool; Adolescent; Diet, Gluten-Free; Autoantibodies; Nutritional Status; Protein Glutamine gamma Glutamyltransferase 2; GTP-Binding Proteins; Transglutaminases; Glutens; Health Status; Infant; Follow-Up Studies; Autoimmunity
PubMed: 38892641
DOI: 10.3390/nu16111708 -
Nutrients May 2024There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development... (Review)
Review
There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.
Topics: Celiac Disease; Humans; Gastrointestinal Microbiome; Intestinal Mucosa; Duodenum
PubMed: 38892582
DOI: 10.3390/nu16111649