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Journal of Medical Virology Dec 2023Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of...
Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.
Topics: Adult; Humans; Middle Aged; Herpes Zoster Oticus; Herpesvirus 3, Human; Cohort Studies; Dizziness; Hyperacusis; Facial Paralysis; Chickenpox; Hearing Loss; Headache; Denmark
PubMed: 38058258
DOI: 10.1002/jmv.29291 -
Clinical Endocrinology Dec 2023Cardiovascular complications and congenital malformations are known traits in Turner syndrome (TS), which increases mortality. Women with TS have varying phenotype and...
OBJECTIVE
Cardiovascular complications and congenital malformations are known traits in Turner syndrome (TS), which increases mortality. Women with TS have varying phenotype and cardiovascular risks. A biomarker assessing the risk for cardiovascular complications could potentially reduce mortality in high-risk TS and reduce screening in TS participants with low cardiovascular risk.
DESIGN, PATIENTS, PARTICIPANTS AND MEASUREMENTS
As part of a study initiated in 2002, 87 TS participants and 64 controls were invited to magnetic resonance imaging of the aorta, anthropometry, and biochemical markers. TS participants were re-examined thrice lastly in 2016. The focus of this paper is the additional measurements of transforming growth factor beta (TGFβ), matrix metalloproteinase (MMP's), tissue inhibitor of matrix metalloproteinase (TIMP), peripheral blood DNA and their associations with TS and the cardiovascular risk and congenital heart disease.
RESULTS
TS participants had lower TGFβ1 and TGFβ2 values compared to controls. snp11547635 heterozygosity was not associated with any biomarkers but was associated with increased risk of aortic regurgitation. TIMP4 and TGFβ1 were correlated with the aortic diameter at several measuring positions. During follow-up, the antihypertensive treatment decreased the descending aortic diameter and increased TGFβ1 and TGFβ2 levels in TS.
CONCLUSION
TGFβ and TIMP's are altered in TS and may play a role in the development of coarctation and dilated aorta. snp11547635 heterozygosity was not found to impact biochemical markers. Further studies should investigate these biomarkers to further unravel the pathogenesis of the increased cardiovascular risk in TS participants.
Topics: Humans; Female; Turner Syndrome; Transforming Growth Factor beta; Aorta; Genotype; Biomarkers; Matrix Metalloproteinases; Tissue Inhibitor of Metalloproteinase-1
PubMed: 36890688
DOI: 10.1111/cen.14907 -
Pediatric Nephrology (Berlin, Germany) Sep 2023There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic...
BACKGROUND
There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS).
METHODS
A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded.
RESULTS
The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them.
CONCLUSIONS
HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Child; Humans; Rituximab; Nephrotic Syndrome; Agammaglobulinemia; Immunosuppressive Agents; Recurrence; Treatment Outcome
PubMed: 37014530
DOI: 10.1007/s00467-023-05913-1 -
Sleep Medicine Clinics Dec 2023There is an increased risk of becoming pregnant through fertility treatments using assisted reproductive technology (ART) during the COVID-19 pandemic. The aim of this... (Review)
Review
There is an increased risk of becoming pregnant through fertility treatments using assisted reproductive technology (ART) during the COVID-19 pandemic. The aim of this review is to gather comprehensive data from the existing literature on the potential risks of fertility management during the pandemic period, and outline strategies to mitigate them, with a focus on the hormonal and surgical procedures of ART. A comprehensive search of the scientific literature on COVID-19 in relation to fertility was conducted in the PubMed database using the keywords "coronavirus," "COVID-19," "SARS-CoV-2" and "pregnancy," "fertility," "urogenital system," "vertical transmission," "assisted human reproduction," "controlled ovarian stimulation," "oocyte retrieval," "in vitro fertilization," "hormones," "surgical procedures," "embryos," "oocytes," "sperm," "semen," "ovary," "testis," "ACE-2 receptor," "immunology," "cytokine storm," and "coagulation," from January 2020-July 2022. Published data on pregnancy and COVID-19, and the interaction of the urogenital system and SARS-CoV-2 is reported. The immunologic and prothrombotic profiles of patients with COVID-19, and their increased risks from controlled ovarian stimulation (COS) and ART surgeries, and how these procedures could facilitate COVID-19 and/or contribute to the severity of the disease by enhancing the cytokine storm are summarized. Strategies to prevent complications during COS that could increase the risks of the disease in pre-symptomatic patients are considered. The impact of SARS-CoV-2 on pre-symptomatic infertile patients presents a challenge to find ways to avoid the increased hormonal, immunologic, and prothrombotic risks presented by the use of COS in ART protocols during the COVID-19 outbreak. Safe ART procedures and recommendations are highlighted.
Topics: Female; Humans; Male; Pregnancy; COVID-19; Cytokine Release Syndrome; SARS-CoV-2; Reproductive Techniques, Assisted
PubMed: 38501521
DOI: 10.1016/j.jsmc.2023.06.012 -
Diabetes Care Aug 2023Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin...
OBJECTIVE
Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity.
RESEARCH DESIGN AND METHODS
We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S.
RESULTS
A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S.
CONCLUSIONS
Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.
Topics: Humans; Diabetes Mellitus, Type 2; Insulin Resistance; Metabolic Syndrome; Prevalence; Polyneuropathies; Diabetic Neuropathies
PubMed: 37335990
DOI: 10.2337/dc23-0079 -
Journal of Translational Medicine Mar 2024Long QT syndrome type 7 (Andersen-Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal...
OBJECTIVE
Long QT syndrome type 7 (Andersen-Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism.
METHODS AND RESULTS
We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs. The spontaneous pulsation rate of myocardial cells in the mutation group was significantly lower than that in the repair CRISPR group, the action potential duration was prolonged, and the Kir2.1 current of the inward rectifier potassium ion channel was decreased, which is consistent with the clinical symptoms of ATS patients. Only ZNF528, a chromatin-accessible TF related to pathogenicity, was continuously regulated beginning from the cardiac mesodermal precursor cell stage (day 4), and continued to be expressed at low levels, which was identified by WGCNA method and verified with ATAC-seq data in the mutation group. Subsequently, it indicated that seven pathways were downregulated (all p < 0.05) by used single sample Gene Set Enrichment Analysis to evaluate the overall regulation of potassium-related pathways enriched in the transcriptome and proteome of late mature CMs. Among them, the three pathways (GO: 0008076, GO: 1990573 and GO: 0030007) containing the mutated gene KCNJ2 is involved that are related to the whole process by which a potassium ion enters the cell via the inward rectifier potassium channel to exert its effect were inhibited. The other four pathways are related to regulation of the potassium transmembrane pathway and sodium:potassium exchange ATPase (p < 0.05). ZNF528 small interfering (si)-RNA was applied to hiPSC-derived cardiomyocytes for CRISPR group to explore changes in potassium ion currents and growth and development related target protein levels that affect disease phenotype. Three consistently downregulated proteins (KCNJ2, CTTN and ATP1B1) associated with pathogenicity were verificated through correlation and intersection analysis.
CONCLUSION
This study uncovers TFs and target proteins related to electrophysiology and developmental pathogenicity in ATS myocardial cells, obtaining novel targets for potential therapeutic candidate development that does not rely on gene editing.
Topics: Humans; Andersen Syndrome; Chromatin; Transcriptome; Induced Pluripotent Stem Cells; Mutation; Myocytes, Cardiac; Potassium
PubMed: 38528561
DOI: 10.1186/s12967-024-05125-7 -
European Journal of Medical Genetics Jun 2024Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS...
Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS type I/III caused by pathogenic variants in TRPS1 and TRPS type II caused by contiguous gene deletions also spanning EXT1 and RAD21. Due to its rarity, knowledge of the clinical course of TRPS remains limited. Therefore, we collected and characterized a case series of 15 TRPS type I patients (median age at diagnosis 15 [interquartile range: 10-18] years, 11 females [73%]) seen at Aarhus University Hospital, Denmark, with a median follow-up period of 10 years. We estimated a minimum point prevalence of 0.5 in 100,000 (95% CI: 0.3-0.8 per 100,000) persons. Common craniofacial features included fine and sparse hair with a high anterior hairline, eyebrows with lateral thinning and a thicker medial part, prominent ears, a bulbous nose tip with small nasal alae, a low-hanging, and often wide columella, and a long philtrum with a thin upper vermillion. Specific skeletal features included short stature and deviating and short fingers with cone-shaped epiphyses and shortened metacarpals on radiographs. The most significant morbidity of the cohort was joint complaints, which were reported by all patients, often already before the TRPS diagnosis was established. We identified ten different TRPS1 variants including both frameshift/nonsense, missense, and splice-site variants, including seven variants not previously reported in the literature. In accordance with previous literature, no genotype-phenotype correlation was identified. The clinical trajectories were heterogeneous involving pediatrics, dermatology, orthopedic surgery, clinical genetics, and/or odontology, emphasizing that close multidisciplinary collaboration is essential for early diagnosis of TRPS and to ensure proper and timely patient care and counseling.
Topics: Adolescent; Child; Female; Humans; Male; DNA-Binding Proteins; Fingers; Hair Diseases; Langer-Giedion Syndrome; Nose; Phenotype; Repressor Proteins; Transcription Factors
PubMed: 38574886
DOI: 10.1016/j.ejmg.2024.104937 -
Medicina Clinica Mar 2024
Topics: Humans; Andersen Syndrome; Long QT Syndrome; Mutation
PubMed: 38044185
DOI: 10.1016/j.medcli.2023.10.021 -
The European Respiratory Journal Jul 2023Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is...
BACKGROUND
Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible.
METHODS
We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 μm (PM), nitrogen dioxide (NO), black carbon (BC) and ozone (O) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density.
RESULTS
138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM (per 0.53 μg·m) and NO (per 3.59 μg·m) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O.
CONCLUSION
Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.
Topics: Humans; Cohort Studies; Nitrogen Dioxide; COVID-19; Environmental Exposure; SARS-CoV-2; Air Pollution; Air Pollutants; Particulate Matter; Hospitalization; Soot; Denmark
PubMed: 37343976
DOI: 10.1183/13993003.00280-2023 -
The British Journal of Ophthalmology Aug 2023Ophthalmic complications are profound in Marfan syndrome (MFS). However, the overall burden is not well described. Our purpose was to evaluate the ocular morbidity in a...
BACKGROUND
Ophthalmic complications are profound in Marfan syndrome (MFS). However, the overall burden is not well described. Our purpose was to evaluate the ocular morbidity in a nationwide perspective.
METHODS
We identified the ocular morbidity in patients with MFS (n=407) by use of Danish national healthcare registers, using number and timing of hospital contacts related to ophthalmic diagnoses, to ophthalmic surgery and to prescriptions for ophthalmic medication. An age-matched and gender-matched background population (n=40 700) was used as comparator.
RESULTS
Among MFS, 56% (226/407) of the patients had at least one registration of an ophthalmic diagnosis as inpatient or outpatient during the study period (HR of 8.0 (95% CI 7.0 to 9.2)). Seven out of 11 main groups of diagnoses were affected, including 'Lens', 'Choroid and retina', 'Ocular muscles, binocular movement, accommodation and refraction', 'Glaucoma', Visual disturbances and blindness', 'Vitreous body and globe', and 'Sclera, cornea, iris and ciliary body'. The number of surgical procedures as well as the use of ophthalmic medication in patients with MFS was significantly increased.
CONCLUSION
This nationwide epidemiological study of ocular morbidity in MFS demonstrates a profound burden and emphasises the need for thorough and experienced ophthalmological surveillance.
Topics: Humans; Marfan Syndrome; Cornea; Refraction, Ocular; Epidemiologic Studies; Morbidity
PubMed: 35318224
DOI: 10.1136/bjophthalmol-2021-320871