ABSTRACT
Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.
Subject(s)
Arsenic , Environmental Exposure , Metabolic Syndrome , Uric Acid , Aged , Female , Humans , Male , Middle Aged , Arsenic/blood , Arsenic/toxicity , China/epidemiology , East Asian People , Environmental Exposure/adverse effects , Metabolic Syndrome/epidemiology , Metabolic Syndrome/chemically induced , Metabolic Syndrome/blood , Uric Acid/bloodABSTRACT
Background: Control of buffalo flies (Haematobia irritans exigua, BFs) relies mainly on chemical methods; however, resistance to insecticides is widespread in BF populations. Breeding for resistance to BFs represents a possible alternative, but direct phenotyping of animals is laborious and often inaccurate. The availability of reliable diagnostic biomarker(s) to identify low BF carrier cattle would facilitate rapid and accurate selection for genetic improvement. However, limited information is available regarding differences amongst cattle in host responses to BF infestation. Methods: This study investigated the variation in Brangus cattle serum proteomic profiles before (naïve) and after peak BF exposure, in low (LF) and high BF burden (HF) cattle. Cattle were phenotyped for susceptibility based on BF counts on multiple dates using visual and photographic techniques. The relative abundance of serum proteins in cattle before and after exposure to BFs was analysed using sequential window acquisition of all theoretical fragment ion mass spectrometry (SWATH-MS). Results: Exposure to BFs elicited similar responses in HF and LF cattle, with 79 and 70 proteins, respectively, showing significantly different abundances post exposure as compared to their relevant naïve groups. The comparison of serum samples from naïve HF and LF cattle identified 44 significantly differentially abundant (DA) proteins, while 37 significantly DA proteins were identified from the comparison between HF and LF cattle post-exposure to BFs. Proteins with higher abundance in naïve LF cattle were enriched in blood coagulation mechanisms that were sustained after exposure to BFs. Strong immune response mechanisms were also identified in naïve LF cattle, whereas these responses developed in HF cattle only after exposure to BF. High BF cattle also showed active anticoagulation mechanisms in response to BF exposure, including downregulation of coagulation factor IX and upregulation of antithrombin-III, which might facilitate BF feeding. Conclusion: Underlying differences in the abundance of proteins related to blood coagulation and immune response pathways could potentially provide indirect indicators of susceptibility to BF infestation and biomarkers for selecting more BF-resistant cattle.
Subject(s)
Proteomics , Animals , Cattle , Proteomics/methods , Disease Susceptibility , Cattle Diseases/immunology , Cattle Diseases/blood , Cattle Diseases/parasitology , Biomarkers/blood , Myiasis/veterinary , Myiasis/immunology , Host-Parasite Interactions/immunology , Blood Proteins/metabolism , Blood Proteins/analysis , ProteomeABSTRACT
BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.
Subject(s)
Hypercalcemia , Multiple Endocrine Neoplasia Type 1 , Parathyroid Neoplasms , Parathyroidectomy , Humans , Multiple Endocrine Neoplasia Type 1/surgery , Multiple Endocrine Neoplasia Type 1/diagnosis , Multiple Endocrine Neoplasia Type 1/complications , Multiple Endocrine Neoplasia Type 1/pathology , Male , Parathyroid Neoplasms/surgery , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/pathology , Parathyroid Neoplasms/complications , Middle Aged , Hypercalcemia/diagnosis , Hypercalcemia/etiology , Hypercalcemia/blood , Adenoma/surgery , Adenoma/diagnosis , Adenoma/pathology , Adenoma/blood , Duodenal Neoplasms/surgery , Duodenal Neoplasms/diagnosis , Duodenal Neoplasms/pathology , Hypophosphatemia/etiology , Hypophosphatemia/diagnosis , Abdominal Pain/etiology , Abdominal Pain/diagnosis , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/blood , Neuroendocrine Tumors/pathology , Diarrhea/etiology , Diarrhea/diagnosis , Early Detection of Cancer/methods , Gastroscopy , Treatment OutcomeABSTRACT
BACKGROUND: The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis. AIM: To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology. METHODS: Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients. RESULTS: Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals (P < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals (P < 0.05) and the expression of triglycerides and fasting blood glucose were increased (P < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals. CONCLUSION: The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.
Subject(s)
Biomarkers , Fatty Acids , Metabolomics , Non-alcoholic Fatty Liver Disease , Humans , Metabolomics/methods , Male , Female , Middle Aged , Fatty Acids/blood , Fatty Acids/metabolism , Biomarkers/blood , Adult , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnosis , China/epidemiology , Lipid Metabolism , Case-Control Studies , Thinness/blood , Thinness/diagnosisABSTRACT
In this editorial, we comment on the article by Chen et al recently published in 2024. We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase (ALT) would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease (MAFLD). This is important given the increasing prevalence of MAFLD and obesity globally. Currently, a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT. The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered, particularly as their study found that 83.12% of their study population with a diagnosis of MAFLD had a normal ALT. The main advantages of screening would be to identify patients and provide intervention early, the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis. However, there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered. Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity, although studies have not yet shown a significant improvement in fibrosis regression. It would also require a huge amount of resource if a reduced ALT level alone was used as criteria; it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk. Currently, there is not a good argument to recommend widespread screening with a reduced ALT level as this is unlikely to be cost-effective. This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories. Although studies previously have suggested a more pragmatic approach in screening those over the age of 60, this is likely to change with the increasing incidence of obesity within the younger age groups. The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.
Subject(s)
Alanine Transaminase , Liver Cirrhosis , Obesity , Humans , Alanine Transaminase/blood , Liver Cirrhosis/blood , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Risk Factors , Obesity/complications , Obesity/blood , Obesity/diagnosis , Obesity/epidemiology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/epidemiology , Mass Screening/methods , Liver/pathology , Prevalence , Biomarkers/bloodABSTRACT
Introduction: The management of Mild Autonomous Cortisol Secretion (MACS) remains a topic of debate among clinicians, with differing opinions on the effectiveness of surgical intervention compared to conservative treatment methods. This meta-analysis provides a comprehensive assessment of available literature to determine the most effective approach for treating this condition. Methods: On December 1, 2023, an exhaustive literature search of English databases Embase, PubMed, the Cochrane Library, Scopus, Web of Science, as well as the Chinese databases China HowNet, Wanfang Database, SinoMed Database, and Weipu Database using the keywords "Mild Autonomous Cortisol Secretion", "Subclinical Cushing's Syndrome", "Subclinical Hypercortisolism", "Mild Cortisol Autonomous Secretion", "Adrenal Incidentaloma", "Surgical Treatment" and "Adrenalectomy". The data were statistically analyzed using STATA version 15.0. Results: In this comprehensive analysis involving 629 patients with MACS, the therapeutic efficacy of adrenalectomy was evident. The meta-analysis results indicate that compared to conservative treatment, surgical intervention more effectively improves obesity indicators in patients: waist circumference (SMD=-0.62, 95% CI: -1.06 to -0.18), BMI (SMD=-0.41, 95% CI: -0.62 to -0.20), enhances glycemic control: fasting blood glucose (SMD=-0.47, 95% CI: -0.68 to -0.26), glycated hemoglobin (SMD=-0.66, 95% CI: -0.95 to -0.38), improves lipid metabolism: triglycerides (SMD=-0.45, 95% CI: -0.73 to -0.16), lowers blood pressure: systolic blood pressure (SMD=-1.04, 95% CI: -1.25 to -0.83), diastolic blood pressure (SMD=-0.89, 95% CI: -1.12 to -0.65), and ameliorates hormonal metabolic disorder: 24h urinary free cortisol (SMD=-1.10, 95% CI: -1.33 to -0.87), ACTH (SMD=2.30, 95% CI: 1.63 to 2.97). All these differences are statistically significant. Conclusion: This meta-analysis shows that, compared to conservative treatment, surgical treatment is more effective in improving obesity indicators, glycemic control, lipid metabolism, reducing blood pressure, and ameliorating hormonal metabolic disorders in patients with MACS. These statistically significant results highlight the importance of considering surgical intervention in the management of patients with MACS. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023492527.
Subject(s)
Adrenalectomy , Cushing Syndrome , Hydrocortisone , Humans , Hydrocortisone/blood , Hydrocortisone/metabolism , Cushing Syndrome/surgery , Cushing Syndrome/metabolism , Cushing Syndrome/therapy , Cushing Syndrome/blood , Conservative Treatment/methods , Treatment Outcome , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/metabolism , Adrenal Gland Neoplasms/bloodABSTRACT
Objective: To investigate the impact of gut microbiota on osteoporosis and identify the mediating role of blood metabolites in this process. Methods: This two-sample Mendelian randomization (MR) study utilized summary level data from genome-wide association studies (GWAS). Gut microbiota GWAS data were obtained from the MiBio-Gen consortium meta-analysis (n=13,266), while osteoporosis summary statistics were sourced from the FinnGen consortium R9 release data (7300 cases and 358,014 controls). Metabolite data, including 1400 metabolites or metabolite ratios, were derived from a study involving 8,299 unrelated individuals. The primary MR method employed was the inverse variance weighted (IVW) method. Reverse MR analysis was conducted on bacteria causally associated with osteoporosis in forward MR. The gut microbiota with the smallest p-value was selected as the top influencing factor for subsequent mediation analysis. A two-step MR approach quantified the proportion of the blood metabolite effect on gut microbiota influencing osteoporosis. IVW and Egger methods were used to assess heterogeneity and horizontal pleiotropy. Results: IVW estimates indicated a suggestive effect of family Christensenellaceae on osteoporosis (odds ratio(OR) = 1.292, 95% confidence interval(CI): 1.110-1.503, P =9.198 × 10-4). Reverse MR analysis revealed no significant causal effect of osteoporosis on family Christensenellaceae (OR = 0.947, 95% CI: 0.836-1.072, P =0.386). The proportion of the effect of family Christensenellaceae on osteoporosis mediated by circulating levels of 3,4-dihydroxybutyrate was 9.727%. No significant heterogeneity or horizontal pleiotropy was detected in the instrumental variables used for MR analysis. Conclusion: This study establishes a causal link between family Christensenellaceae and osteoporosis, with a minor proportion of the effect mediated by elevated circulating levels of 3,4-dihydroxybutyrate. Further randomized controlled trials (RCTs) are warranted to validate this conclusion.
Subject(s)
Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Osteoporosis , Humans , Osteoporosis/genetics , Osteoporosis/blood , Polymorphism, Single Nucleotide , Female , Risk FactorsABSTRACT
OBJECTIVE: This article focuses on the clinical features and diagnostic evaluations that accurately identify patients with ever-expanding forms of antibody-defined encephalitis. Forms of autoimmune encephalitis are more prevalent than infectious encephalitis and represent treatable neurologic syndromes for which early immunotherapies lead to the best outcomes. LATEST DEVELOPMENTS: A clinically driven approach to identifying many autoimmune encephalitis syndromes is feasible, given the typically distinctive features associated with each antibody. Patient demographics alongside the presence and nature of seizures, cognitive impairment, psychiatric disturbances, movement disorders, and peripheral features provide a valuable set of clinical tools to guide the detection and interpretation of highly specific antibodies. In turn, these clinical features in combination with serologic findings and selective paraclinical testing, direct the rationale for the administration of immunotherapies. Observational studies provide the mainstay of evidence guiding first- and second-line immunotherapy administration in autoimmune encephalitis and, whereas these typically result in some clinical improvements, almost all patients have residual neuropsychiatric deficits, and many experience clinical relapses. An improved pathophysiologic understanding and ongoing clinical trials can help to address these unmet medical needs. ESSENTIAL POINTS: Antibodies against central nervous system proteins characterize various autoimmune encephalitis syndromes. The most common targets include leucine-rich glioma inactivated protein 1 (LGI1), N-methyl-d-aspartate (NMDA) receptors, contactin-associated proteinlike 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65). Each antibody-associated autoimmune encephalitis typically presents with a recognizable blend of clinical and investigation features, which help differentiate each from alternative diagnoses. The rapid expansion of recognized antibodies and some clinical overlaps support panel-based antibody testing. The clinical-serologic picture guides the immunotherapy regime and offers valuable prognostic information. Patient care should be delivered in conjunction with autoimmune encephalitis experts.
Subject(s)
Encephalitis , Hashimoto Disease , Humans , Encephalitis/diagnosis , Encephalitis/therapy , Encephalitis/immunology , Hashimoto Disease/diagnosis , Hashimoto Disease/therapy , Hashimoto Disease/immunology , Female , Autoantibodies/blood , Autoantibodies/immunology , Male , Immunotherapy/methods , Adult , Autoimmune Diseases of the Nervous System/diagnosis , Autoimmune Diseases of the Nervous System/therapy , Autoimmune Diseases of the Nervous System/immunology , Autoimmune Diseases of the Nervous System/physiopathology , Middle AgedABSTRACT
OBJECTIVE: This article reviews the clinical features, MRI characteristics, diagnosis, and treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The main differences between these disorders and multiple sclerosis (MS), the most common demyelinating disease of the central nervous system (CNS), are also highlighted. LATEST DEVELOPMENTS: The past 20 years have seen important advances in understanding rare demyelinating CNS disorders associated with AQP4 IgG and myelin oligodendrocyte glycoprotein (MOG) IgG. The rapidly expanding repertoire of immunosuppressive agents approved for the treatment of AQP4-NMOSD and emerging as potentially beneficial in MOGAD mandates prompt recognition of these diseases. Most of the recent literature has focused on the identification of clinical and MRI features that help distinguish these diseases from each other and MS, simultaneously highlighting major diagnostic pitfalls that may lead to misdiagnosis. An awareness of the limitations of currently available assays for AQP4 IgG and MOG IgG detection is fundamental for identifying rare false antibody positivity and avoiding inappropriate treatments. For this purpose, diagnostic criteria have been created to help the clinician interpret antibody testing results and recognize the clinical and MRI phenotypes associated with AQP4-NMOSD and MOGAD. ESSENTIAL POINTS: An awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. The growing availability of effective treatment options will lead to personalized therapies and improved outcomes.
Subject(s)
Myelin-Oligodendrocyte Glycoprotein , Neuromyelitis Optica , Humans , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/immunology , Neuromyelitis Optica/diagnostic imaging , Myelin-Oligodendrocyte Glycoprotein/immunology , Aquaporin 4/immunology , Female , Autoantibodies/blood , Male , Adult , Magnetic Resonance Imaging , Middle AgedABSTRACT
OBJECTIVE: Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. LATEST DEVELOPMENTS: Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. ESSENTIAL POINTS: It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.
Subject(s)
Autoantibodies , Glutamate Decarboxylase , Stiff-Person Syndrome , Humans , Stiff-Person Syndrome/diagnosis , Stiff-Person Syndrome/immunology , Stiff-Person Syndrome/physiopathology , Stiff-Person Syndrome/blood , Glutamate Decarboxylase/immunology , Autoantibodies/blood , Male , Female , Muscle Rigidity/diagnosis , Muscle Rigidity/immunology , Muscle Rigidity/drug therapy , Encephalomyelitis/diagnosis , Encephalomyelitis/immunology , Encephalomyelitis/blood , Middle Aged , Adult , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/immunology , Cerebellar Ataxia/blood , Cerebellar Ataxia/physiopathology , Limbic Encephalitis/diagnosis , Limbic Encephalitis/immunology , Limbic Encephalitis/therapy , Limbic Encephalitis/blood , Limbic Encephalitis/physiopathologyABSTRACT
OBJECTIVE: This article reviews autoimmune neuromuscular disorders and includes an overview of the diagnostic approach, especially the role of antibody testing in a variety of neuropathies and some other neuromuscular disorders. LATEST DEVELOPMENTS: In the past few decades, multiple antibody biomarkers associated with immune-mediated neuromuscular disorders have been reported. These biomarkers are not only useful for better understanding of disease pathogenesis and allowing more timely diagnosis but may also aid in the selection of an optimal treatment strategy. ESSENTIAL POINTS: Recognition of autoimmune neuromuscular conditions encountered in inpatient or outpatient neurologic practice is very important because many of these disorders are reversible with prompt diagnosis and early treatment. Antibodies are often helpful in making this diagnosis. However, the clinical phenotype and electrodiagnostic testing should be taken into account when ordering antibody tests or panels and interpreting the subsequent results. Similar to other laboratory investigations, understanding the potential utility and limitations of antibody testing in each clinical setting is critical for practicing neurologists.
Subject(s)
Autoantibodies , Neuromuscular Diseases , Humans , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/immunology , Autoantibodies/blood , Autoantibodies/immunology , Male , Female , Middle Aged , Adult , Autoimmune Diseases of the Nervous System/immunology , Autoimmune Diseases of the Nervous System/diagnosis , Autoimmune Diseases/immunology , Autoimmune Diseases/diagnosis , Aged , Biomarkers/bloodABSTRACT
OBJECTIVE: This article reviews the clinical and antibody spectrum of autoimmune cerebellar ataxia and other autoimmune movement disorders. It highlights characteristic phenotypes and red flags to the diagnosis and how these rare, but treatable, disorders are integrated into a differential diagnosis. LATEST DEVELOPMENTS: An increasing number of neuronal antibodies have been identified in patients with cerebellar ataxia, for example, against Kelch-like protein 11 (KLHL11), seizure-related 6 homolog-like 2, septin-3 and septin-5, or tripartite motif containing protein 9 (TRIM9), TRIM46, and TRIM67. Ig-like cell adhesion molecule 5 (IgLON5) antibody-associated syndromes have emerged as an important alternative diagnostic consideration to various neurodegenerative diseases such as Huntington disease or atypical parkinsonism. Opsoclonus-myoclonus syndrome emerged as the most relevant parainfectious movement disorder related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ESSENTIAL POINTS: Autoimmune cerebellar ataxia and other autoimmune movement disorders encompass a broad spectrum of different clinical syndromes, antibodies, and immunopathophysiologic mechanisms. Clinical acumen is key to identifying the cases that should undergo testing for neuronal antibodies. Given the overlap between phenotypes and antibodies, panel testing in serum and CSF is recommended.
Subject(s)
Movement Disorders , Humans , Movement Disorders/diagnosis , Movement Disorders/immunology , Autoimmune Diseases/diagnosis , Autoimmune Diseases/immunology , Female , Male , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/immunology , Middle Aged , Adult , Autoantibodies/blood , Autoantibodies/cerebrospinal fluid , COVID-19/immunology , COVID-19/diagnosis , COVID-19/complications , Diagnosis, Differential , Autoimmune Diseases of the Nervous System/diagnosis , Autoimmune Diseases of the Nervous System/immunologyABSTRACT
BACKGROUND AND OBJECTIVES: To analyze the ability of prehospital lactate levels to predict 2-day in-hospital mortality in patients with traumatic brain injury (TBI), severe TBI (Glasgow Coma Scale (GCS) ≤ 8 points), and mild or moderate TBI (GCS ≥ 9 points). Second, 90-day mortality was also explored. METHODS: This was a prospective, multicenter, emergency medical services (EMSs) delivery, ambulance-based, derivation-validation cohort study developed in 5 tertiary hospitals (Spain), from November 1, 2019, to July 31, 2022. Patients were recruited from among all phone requests for emergency assistance among adults who were later evacuated to referral hospitals with acute TBI. The exclusion criteria were minors, pregnancy, trauma patients without TBI, delayed presentations, patients were discharged in situ, participants with cardiac arrest, and unavailability to obtain a blood sample. The primary outcome was all-cause 2-day in-hospital mortality and 90-day mortality in patients with moderate or mild TBI compared with patients with severe TBI. Clinical and analytical parameters (lactate and glucose) were collected. The discriminative power (area under the receiver operating characteristic curve [AUC]) and calibration curve were calculated for 2 geographically separated cohorts. RESULTS: A total of 509 patients were ultimately included. The median age was 58 years (interquartile range: 43-75), and 167 patients were female (32.8%). The primary outcome occurred in 9 (2.2%) of 415 patients with moderate or mild TBI and in 42 (44.7%) of 94 patients with severe TBI. The predictive capacity of the lactate concentration was globally validated in our cohort, for which the AUC was 0.874 (95% CI 0.805-0.942) for the validation cohort. The ability of the GCS score to predict lactate concentration was greater in patients with a GCS score ≥9 points, with an AUC of 0.925 (95% CI 0.808-1.000) and a negative predictive value of 99.09 (95% CI 98.55-99.64) in the validation cohort. CONCLUSION: Our results show the benefit of using lactate in all patients with TBI, particularly in those with a GCS ≥9 points. Routine incorporation of lactate in the screening of patients with TBI could presumably reduce mortality and deterioration rates because of quicker and better identification of patients at risk.
Subject(s)
Ambulances , Brain Injuries, Traumatic , Hospital Mortality , Lactic Acid , Humans , Brain Injuries, Traumatic/mortality , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/diagnosis , Female , Male , Middle Aged , Lactic Acid/blood , Aged , Prospective Studies , Adult , Emergency Medical Services , Glasgow Coma Scale , Predictive Value of Tests , Cohort Studies , Spain/epidemiologyABSTRACT
Hyperhomocysteinaemia (elevated blood levels of the amino acid homocysteine) attracted the interest of researchers in the middle of the 20th century. At first. Butz and du Vigneaud in 1932 described a disorder of methionine metabolism in children, which was manifested by homocysteinuria (homocysteine is not normally detected in the urine). In 1962 Cavon and Neil found that homocysteinuria in children is associated with a defect in cystathione-B-synthase and manifests early development of atherosclerosis. It is quite possible that these facts would have remained unnoticed by the medical community had it not been for further research by Kilmer McQuilley, a professor in the Department of Pathology at Harvard Medical School. The scientist suggested that while high concentrations of homocysteine could damage blood vessels in young people, it was likely that lower concentrations of homocysteine, acting over a longer period of time, could cause cardiovascular disease in adults. Subsequent studies enabled him to formulate the "homocysteine" theory of atherosclerosis and to publish its main points in 1969. Hyperhomocysteinaemia in young men has been shown to cause damage to the endothelium of blood vessels, and consequently males face the consequent equally global problem of developing erectile dysfunction. Erection is a state regulated by a neurovascular process, characterized by blood filling of the cavernous bodies, provided by neural and humoral mechanisms occurring at different levels of the nervous system. Erectile dysfunction (ED) refers to the inability to achieve and maintain an erection at a level necessary to ensure satisfactory sexual intercourse, Although ED is not life-threatening. it is a serious psychological and physiological problem, and it has now been shown to correlate the quality of intimate life with general health and even with life expectancy, In the USA alone, ED is reported in 20-30 million men, and the prevalence of these disorders increases with age. A study of the homocysteine level of multidisciplinary hospital patients was used as the main marker. The work used laboratory and statistical research methods, as well as analysis and synthesis methods. Using patient analyses, laboratory and statistical data, it has been shown that hyperhomosysteinaemia is one of the molecular mechanisms in the development of erectile dysfunction.
Subject(s)
Erectile Dysfunction , Homocysteine , Hyperhomocysteinemia , Humans , Hyperhomocysteinemia/complications , Male , Erectile Dysfunction/etiology , Homocysteine/bloodABSTRACT
Type 2 diabetes mellitus is the most widespread type of diabetes, mainly affecting adults. Long-term complications are related to the progression of type 2 diabetes mellitus. Metformin is a key treatment option for type 2 diabetes. OBJECTIVES: To evaluate serum irisin, visfatin, and RBP4 levels and to determine the effects of metformin treatment on irisin, visfatin, and RBP4 levels in patients with type 2 diabetes mellitus (Type 2 DM). MATERIAL AND METHODS: A total of 70 patients with type 2 diabetes mellitus, aged between 48 and 82 years were enrolled in the current study. Serum collected and irisin, visfatin, and RBP4 levels were measured, in Type 2 DM patients and control, using the ELISA Kit. RESULTS: The findings observed that there were significantly increased levels of irisin, visfatin, and RBP4 in patients with T2DM when compared with control groups. After 3 months of metformin treatment, irisin levels significantly decreased irisin, visfatin, and RBP4 in patients with T2DM when compared before treatment. Receiver operator characteristic curve investigation shows the levels of visfatin, and irisin are the best biomarkers differentiating subjects with T2DM. CONCLUSION: In patients with type 2 diabetes, 3 months of treatment with metformin reduces levels of Irisin, Visfatin, and RBP4.The clinical significance of these findings remains to be investigated.
Subject(s)
Biomarkers , Diabetes Mellitus, Type 2 , Fibronectins , Hypoglycemic Agents , Metformin , Nicotinamide Phosphoribosyltransferase , Retinol-Binding Proteins, Plasma , Humans , Metformin/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Middle Aged , Fibronectins/blood , Nicotinamide Phosphoribosyltransferase/blood , Aged , Male , Female , Biomarkers/blood , Retinol-Binding Proteins, Plasma/metabolism , Retinol-Binding Proteins, Plasma/analysis , Hypoglycemic Agents/therapeutic use , Aged, 80 and over , Adipokines/blood , CytokinesABSTRACT
Hyperglycemia and hyperinsulinemia in type 2 diabetes result in complications exacerbated by oxidative stress, leading to cardiovascular, nephropathic, neuropathic, and retinopathic problems. Substance P(SP), a natural neuropeptide, inhibits cell death and enhances cell growth during oxidative or inflammatory stress, suggesting a potential role in reducing diabetic complications. Objective -investigate serum levels of SP, total antioxidant status (TAS), glycemic measures, and lipid profiles in non-obese type 2 diabetic patients and evaluate the relationships involving these biomarkers. MATERIAL AND METHOD: A case-control study involved 85 adult subjects (46males & 39females), aged (30-60) year, included two groups; diabetic group:53(males & females) non-obese type 2 diabetic patients, healthy group: Apparently healthy subjects of 32 individuals chosen from the general population and matched with patients age, sex and BMI. RESULTS: The results showed that patients' glucose levels increased as percentage increase of (Ë141%),mild elevated insulin levels (Ë50%), higher insulin resistance (Ë250%), the lipid parameters exhibited disruption in comparison to the control group, in diabetic group, the serum levels of TAS, SP decreased considerably in comparison to the control group. CONCLUSION: As evidenced by the outcomes; the TAS showed significant negative correlations with fasting serum glucose and low-density lipoprotein, and positive correlations with high-density lipoprotein. Neither the glycemic indices nor the lipid profiles or TAS demonstrated any notable associations with SP levels. This suggests that while SP levels are reduced in type 2 diabetes, they do not appear to be directly linked with the measured biomarkers.
Subject(s)
Antioxidants , Biomarkers , Blood Glucose , Diabetes Mellitus, Type 2 , Substance P , Humans , Diabetes Mellitus, Type 2/blood , Female , Male , Middle Aged , Adult , Substance P/blood , Biomarkers/blood , Case-Control Studies , Antioxidants/metabolism , Blood Glucose/metabolism , Insulin Resistance , Oxidative Stress , Insulin/bloodABSTRACT
BACKGROUND: Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. OBJECTIVE: With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. METHODS: A total of 25 panelists, including adult and child neurologists, participated in the study. RESULTS: The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSION: The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.
ANTECEDENTES: Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. OBJETIVO: Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. MéTODOS: Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. RESULTADOS: Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSãO: Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.
Subject(s)
Consensus , Encephalitis , Humans , Encephalitis/diagnosis , Encephalitis/therapy , Encephalitis/immunology , Brazil , Child , Adult , Hashimoto Disease/diagnosis , Hashimoto Disease/therapy , Delphi Technique , Autoantibodies/bloodABSTRACT
Myelodysplastic syndromes (MDS) present with polymorphic and non-specific diagnostic features Research parametersfrom hematology analyzers may be useful to discriminate MDS-related cytopenia.Parameters such as Neu X (related to the cytoplasmic complexity) and Neu Y (related to nucleic acid content) show promise to detect dysplasia of MDS and aid to recognize MDS from cytopenias of other etiologies.
Subject(s)
Myelodysplastic Syndromes , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/blood , Humans , Blood Cell CountABSTRACT
Clinical flow cytometry plays a vital role in the diagnosis and monitoring of various red blood cell disorders. The high throughput, precision, and automation potential of this technique allows for cost-effective and timely analysis compared to older and more manual test methods. Flow cytometric analysis serves as the gold standard diagnostic method for multiple hematological disorders, especially in clinical scenarios where an assay needs to have high sensitivity, high specificity, and a short turnaround time. In this review, we discuss the role of flow cytometric analysis in paroxysmal nocturnal hemoglobinuria, fetal-maternal hemorrhage, and hereditary spherocytosis.
Subject(s)
Flow Cytometry , Spherocytosis, Hereditary , Humans , Flow Cytometry/methods , Spherocytosis, Hereditary/diagnosis , Spherocytosis, Hereditary/blood , Erythrocytes/cytology , Hemoglobinuria, Paroxysmal/diagnosis , Hemoglobinuria, Paroxysmal/blood , Hematologic Diseases/diagnosis , Hematologic Diseases/blood , Pregnancy , Female , Fetomaternal Transfusion/diagnosis , Fetomaternal Transfusion/bloodABSTRACT
The term 'routine coagulation' typically applies to hemostasis tests routinely performed in hematology laboratories, often available 24/7, and potentially ordered urgently. These tests would comprise of the prothrombin time (PT), the PT converted to an international normalized ratio, the activated partial thromboplastin time (often called partial thromboplastin time in North American laboratories) and potentially the thrombin time, the D-dimer assay, and fibrinogen assays. Although other tests could feasibly be offered (testing feasible), there are good reasons for not including all of these other tests in all routine coagulation laboratories.