An ocular lesion of unknown aetiology.
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ABSTRACT:
SUBMITTER: Drosslerova M
PROVIDER: S-EPMC8291921 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five cases who underwent liver transplantation, we detected high levels of adeno-associated virus 2 (AAV2) in the explanted livers. AAV2 was also detected at high levels in blood from 10/11 non-transplanted cases. Low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), both of which enable AAV2 lytic replication, were also found in the five explanted livers and blood from 15/17 and 6/9 respectively, of the 23 non-transplant cases tested. In contrast, AAV2 was detected at low titre in 6/100 whole bloods from child controls from cohorts with presence or absence of hepatitis and/or adenovirus infection. Our data show an association of AAV2 at high titre in blood or liver tissue, with unexplained hepatitis in children infected in the recent HAdV-F41 outbreak. We were unable to find evidence by electron microscopy, immunohistochemistry or proteomics of HAdV or AAV2 viral particles or proteins in explanted livers, suggesting that hepatic pathology is not due to direct lytic infection by either virus. The potential that AAV2, although not previously associated with disease, may, together with HAdV-F41 and/or HHV-6, be causally implicated in the outbreak of unexplained hepatitis, requires further investigation.
2023-04-04 | PXD035925 | Pride
Project description:AimsAtrioventricular block (AVB) of unknown aetiology is rare in the young, and outcome in these patients is unknown. We aimed to assess long-term morbidity and mortality in young patients with AVB of unknown aetiology.Methods and resultsWe identified all Danish patients younger than 50 years receiving a first pacemaker due to AVB between January 1996 and December 2015. By reviewing medical records, we included patients with AVB of unknown aetiology. A matched control cohort was established. Follow-up was performed using national registries. The primary outcome was a composite endpoint consisting of death, heart failure hospitalization, ventricular tachyarrhythmia, and cardiac arrest with successful resuscitation. We included 517 patients, and 5170 controls. Median age at first pacemaker implantation was 41.3 years [interquartile range (IQR) 32.7-46.2 years]. After a median follow-up of 9.8 years (IQR 5.7-14.5 years), the primary endpoint had occurred in 14.9% of patients and 3.2% of controls [hazard ratio (HR) 3.8; 95% confidence interval (CI) 2.9-5.1; P < 0.001]. Patients with persistent AVB at time of diagnosis had a higher risk of the primary endpoint (HR 10.6; 95% CI 5.7-20.0; P < 0.001), and risk was highest early in the follow-up period (HR 6.8; 95% CI 4.6-10.0; P < 0.001, during 0-5 years of follow-up).ConclusionAtrioventricular block of unknown aetiology presenting before the age of 50 years and treated with pacemaker implantation was associated with a three- to four-fold higher rate of the composite endpoint of death or hospitalization for heart failure, ventricular tachyarrhythmia, or cardiac arrest with successful resuscitation. Patients with persistent AVB were at higher risk. These findings warrant improved follow-up strategies for young patients with AVB of unknown aetiology.
| S-EPMC8169155 | biostudies-literature
Project description: Not available
| S-EPMC10425936 | biostudies-literature
Project description:BackgroundEncephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.MethodsWe measured 38 mediators in serum and cerebrospinal fluid (CSF) of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.ResultsHeat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO) concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006). Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03). Multivariate analysis selected serum MPO; classifying 31 (91%) as infectious (p = 0.008) and 17 (85%) as unknown (p = 0.009) as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85%) as infectious as opposed to immune-mediated (p = 0.036). CSF neutrophils were detected in eight (62%) infective and one (14%) immune-mediated cases (p = 0.004); CSF MPO correlated with neutrophils (p<0.0001).ConclusionsMediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.
| S-EPMC4726626 | biostudies-literature
Project description:The composition of the upper respiratory tract microbiome may play an important role in the development of lower respiratory tract infections. Here, we characterised the microbiome of the nasopharynx and oropharynx of hospitalised patients with community-acquired pneumonia (CAP) with unknown aetiology in an attempt to obtain insight into the aetiology of CAP. A random sample of 10 patients hospitalised with CAP previously enrolled in a separate clinical trial (ClinicalTrials.gov registry, Study ID: NCT01248715) in which a complete microbiological workup was not able to define an aetiology were analysed in this pilot study. This larger trial (n = 1,221) enrolled patients from 9 adult hospitals in Louisville, Kentucky, USA. Nasopharyngeal and oropharyngeal swabs were obtained for metagenomic analysis. Polymerase chain reaction (PCR) for Streptococcus pneumoniae was performed in all patients. One patient had a distinct nasophararyngeal microbiome consisting largely of Haemophilus influenzae. This was the only patient with a negative PCR for S. pneumoniae in both nasophararyngeal and oropharyngeal specimens. Overall, substantial differences were found between nasophararyngeal and oropharyngeal microbiomes. The upper respiratory tract microbiome of only one patient suggested H. influenzae as a probable aetiology of CAP. Although this was a pilot study of only 10 patients, the presence of S. pneumoniae in the upper respiratory tract of the other 9 patients warrants further investigation.
| S-EPMC5922341 | biostudies-literature
Project description:Hepatitis is a general term meaning inflammation of the liver, which can be caused by a variety of viruses. However, a substantial number of cases remain with unknown aetiology. We analysed the serum of patients with clinical signs of hepatitis using a metagenomics approach to characterize their viral species composition. Four pools of patients with hepatitis without identified aetiological agents were evaluated. Additionally, one pool of patients with hepatitis E (HEV) and pools of healthy volunteers were included as controls. A high diversity of anelloviruses, including novel sequences, was found in pools from patients with hepatitis of unknown aetiology. Moreover, viruses recently associated with gastroenteritis as sapovirus GV.2 and astrovirus VA3 were also detected only in those pools. Besides, most of the HEV genome was recovered from the HEV pool. Finally, GB virus C and human endogenous retrovirus were found in the HEV and healthy pools. Our study provides an overview of the virome in serum from hepatitis patients suggesting a potential role of these viruses not previously described in cases of hepatitis. However, further epidemiologic studies are necessary to confirm their contribution to the development of hepatitis.
| S-EPMC5628893 | biostudies-literature
Project description:BackgroundAn outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children during 2022 was subsequently linked to infections with adenovirus-associated virus 2 and other 'helper viruses', including human adenovirus. It is possible that evidence of such an outbreak could be identified at a population level based on routine data captured by electronic health records (EHR).MethodsWe used anonymised EHR to collate retrospective data for all emergency presentations to Oxford University Hospitals NHS Foundation Trust in the UK, between 2016-2022, for all ages from 18 months and older. We investigated clinical characteristics and temporal distribution of presentations of acute hepatitis and of adenovirus infections based on laboratory data and clinical coding. We relaxed the stringent case definition adopted during the AS-Hep-UA to identify all cases of acute hepatitis with unknown aetiology (termed AHUA). We compared events within the outbreak period (defined as 1st Oct 2021-31 Aug 2022) to the rest of our study period.ResultsOver the study period, there were 903,433 acute presentations overall, of which 391 (0.04%) were classified as AHUA. AHUA episodes had significantly higher critical care admission rates (p < 0.0001, OR = 41.7, 95% CI:26.3-65.0) and longer inpatient admissions (p < 0.0001) compared with the rest of the patient population. During the outbreak period, significantly more adults (≥ 16 years) were diagnosed with AHUA (p < 0.0001, OR = 3.01, 95% CI: 2.20-4.12), and there were significantly more human adenovirus (HadV) infections in children (p < 0.001, OR = 1.78, 95% CI:1.27-2.47). There were also more HAdV tests performed during the outbreak (p < 0.0001, OR = 1.27, 95% CI:1.17-1.37). Among 3,707 individuals who were tested for HAdV, 179 (4.8%) were positive. However, there was no evidence of more acute hepatitis or increased severity of illness in HadV-positive compared to negative cases.ConclusionsOur results highlight an increase in AHUA in adults coinciding with the period of the outbreak in children, but not linked to documented HAdV infection. Tracking changes in routinely collected clinical data through EHR could be used to support outbreak surveillance.
| S-EPMC11251388 | biostudies-literature
Project description:Background: Diagnosing stroke as a cause of acute vertigo, dizziness, or double vision remains a challenge, because symptom characteristics can be variable. The purpose of this study was to prospectively investigate lesion-symptom relationships in patients with acute vestibular or ocular motor stroke. Methods: Three hundred and fifty one patients with acute and isolated vestibular or ocular motor symptoms of unclear etiology were enrolled in the EMVERT lesion trial. Symptom quality was assessed by the chief complaint (vertigo, dizziness, double vision), symptom intensity by the visual analog scale, functional impairment by EQ-5D-5L, and symptom duration by daily rating. Acute vestibular and ocular motor signs were registered by videooculography. A standardized MRI (DWI-/FLAIR-/T2-/T2*-/3D-T1-weighted sequences) was recorded within 7 days of symptom onset. MRIs with DWI lesions were further processed for voxel-based lesion-symptom mapping (VLSM). Results: In 47 patients, MRI depicted an acute unilateral stroke (13.4%). The chief complaints were dizziness (42.5%), vertigo (40.4%) and double vision (17.0%). Lesions in patients with vertigo or dizziness showed a large overlap in the cerebellar hemisphere. VLSM indicated that strokes in the medial cerebellar layers 7b, 8, 9 were associated with vertigo, strokes in the lateral cerebellar layer 8, crus 1, 2 with dizziness, and pontomesencephalic strokes with double vision. Symptom intensity and duration varied largely between patients. Higher symptom intensity and longer duration were associated with medial cerebellar lesions. Hemispheric lesions of the cortex were rare and presented with milder symptoms of shorter duration. Conclusions: Prospective evaluation of patients with acute vestibular or ocular motor stroke revealed that symptom quality, intensity and duration were not suited to differentiating peripheral from central etiologies. Lesions in the lateral cerebellum, thalamus, or cortex presented with unspecific, mild and transient symptoms prone to being misdiagnosed.
| S-EPMC7424024 | biostudies-literature
Project description:In a recent issue of Clinical Kidney Journal (CKJ), Gutierrez-Peña et al. reported a high incidence and prevalence of advanced chronic kidney disease (CKD) in Aguascalientes, Mexico. This contradicts Global Burden of Disease estimates, which should be updated. A key component of this high burden of CKD relates to young people ages 20-40 years in whom the cause of CKD was unknown [CKD of unknown aetiology (CKDu)]. The incidence of kidney replacement therapy in this age group in Aguascalientes is among the highest in the world, second only to Taiwan. However, high-altitude Aguascalientes, with a year-round average temperature of 19°C, does not fit the geography of other CKDu hotspots. Furthermore, kidney biopsies in young people showed a high prevalence of focal segmental glomerulosclerosis. Potential causes of CKDu in Aguascalientes include the genetic background (no evidence, although podocytopathy genes should be explored) and environmental factors. The highest prevalence of CKD was found in Calvillo, known for guava farming. Thus guava itself, known to contain bioactive, potentially nephrotoxic molecules and pesticides, should be explored. Additionally, there are reports of water sources in Aguascalientes contaminated with heavy metals and/or pesticides. These include fluoride (increased levels found in Calvillo drinking water) as well as naturally occurring arsenic, among others. Fluoride may accumulate in bone and cause kidney disease years later, and maternal exposure to excess fluoride may cause kidney disease in offspring. We propose a research agenda to clarify the cause of CKDu in Aguascalientes that should involve international funders. The need for urgent action to identify and stem the cause of the high incidence of CKD extends to other CKD hotspots in Mexico, including Tierra Blanca in Veracruz and Poncitlan in Jalisco.
| S-EPMC8573004 | biostudies-literature
Project description:BackgroundChronic Kidney Disease of unknown origin (CKDu) excludes known primary renal conditions or systemic disease (such as diabetes mellitus or hypertension). Prominence of CKDu has been noted for some decades in Sri Lanka, especially among men in particular rural areas, prompting many studies directed towards environmental causation. This article critically reviews relevant primary studies.MethodsArticles for this literature review (n = 86) were found by searching Medline, Embase, Global Health and ProQuest databases over 2000-2020 utilizing a standard algorithm. Articles were critiqued according to criteria for diagnosis of CKDu, aetiological agents investigated, analytic methods employed and findings.ResultsCriteria for diagnosis of CKDu varied significantly, including pre-selection by proteinuria, eGFR and biopsy proven interstitial nephritis. Prevalence studies have been largely conducted in the North Central Province, with recent studies demonstrating the presence of CKDu in other regions. Aetiological factors investigated in primary studies included water source, use of agrochemicals, agricultural work, heavy metals, snake bites, ayurvedic medication, heat stress, infectious diseases and usage of tobacco and betel leaf. There is no conclusive evidence for any one aetiological agent despite consistent evidence of distal factors such as male sex, rural residence and farming.ConclusionsThe current body of evidence for any aetiological agent as the cause of CKDu in Sri Lanka is limited. Further research with stronger study designs is necessary to increase knowledge of aetiology of CKDu in Sri Lanka to identify and eliminate exposure to possible causative agent(s) prior to concluding that the disease is multifactorial.
| S-EPMC9298898 | biostudies-literature