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Ultrasound in Obstetrics & Gynecology :... Nov 2023To investigate the national prevalence and prenatal detection rate (DR) of major congenital heart disease (mCHD) in twin pregnancies without twin-to-twin transfusion...
OBJECTIVE
To investigate the national prevalence and prenatal detection rate (DR) of major congenital heart disease (mCHD) in twin pregnancies without twin-to-twin transfusion syndrome (TTTS)-associated CHD in a Danish population following a standardized prenatal screening program.
METHODS
This was a national registry-based study of data collected prospectively over a 10-year period. In Denmark, all women with a twin pregnancy are offered standardized screening and surveillance programs in addition to first- and second-trimester screening for aneuploidies and malformation, respectively: monochorionic (MC) twins every 2 weeks from gestational week 15 and dichorionic (DC) twins every 4 weeks from week 18. The data were retrieved from the Danish Fetal Medicine Database and included all twin pregnancies from 2009-2018, in which at least one fetus had a pre- and/or postnatal mCHD diagnosis. mCHD was defined as CHD requiring surgery within the first year of life, excluding ventricular septal defects. All pregnancy data were pre- and postnatally validated in the local patient files at the four tertiary centers covering the entire country.
RESULTS
A total of 60 cases from 59 twin pregnancies were included. The prevalence of mCHD was 4.6 (95% CI, 3.5-6.0) per 1000 twin pregnancies (1.9 (95% CI, 1.3-2.5) per 1000 live births). The prevalences for DC and MC were 3.6 (95% CI, 2.6-5.0) and 9.2 (95% CI, 5.8-13.7) per 1000 twin pregnancies, respectively. The national prenatal DR of mCHD in twin pregnancies for the entire period was 68.3%. The highest DRs were in cases with univentricular hearts (100%) and the lowest with aortopulmonary window, total anomalous pulmonary venous return, Ebstein's anomaly, aortic valve stenosis and coarctation of the aorta (0-25%). Mothers of children with prenatally undetected mCHD had a significantly higher body mass index (BMI) compared to mothers of children with a prenatally detected mCHD (median, 27 kg/m and 23 kg/m , respectively; P = 0.02).
CONCLUSIONS
The prevalence of mCHD in twins was 4.6 per 1000 pregnancies and was higher in MC than DC pregnancies. The prenatal DR of mCHD in twin pregnancies was 68.3%. Maternal BMI was higher in cases of prenatally undetected mCHD. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Child; Humans; Female; Pregnancy, Twin; Prevalence; Gestational Age; Heart Defects, Congenital; Twins, Dizygotic; Denmark; Retrospective Studies
PubMed: 37191390
DOI: 10.1002/uog.26249 -
Scientific Reports Dec 2023Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the...
Characterization of the pathophysiology of ARDS following chlorine gas inhalation in clinically relevant translational large animal models is essential, as the opportunity for clinical trials in this type of trauma is extremely limited. To investigate Cl concentration and gender-dependent ARDS severity. Sheep (n = 54) were exposed to air or Cl premixed in air at a concentration of 50, 100, 200, and 300 ppm for 30 min under anesthesia/analgesia and monitored for an additional 48 h in a conscious state. Cardiopulmonary variables and survival endpoints were compared between male and female sheep. Overall there were no significant differences in the responses of female and male sheep except pulmonary oxygenation tended to be better in the male sheep (300 ppm group), and the pulmonary arterial pressure was lower (200 ppm group). The onset of mild ARDS (200 < PaO/FiO ≤ 300) was observed at 36 h post exposure in the 50 ppm group, whereas the 100 ppm group developed mild and moderate (100 ≤ PaO/FiO ≤ 200) ARDS by 12 and 36 h after injury, respectively. The 200 ppm and 300 ppm groups developed moderate ARDS within 6 and 3 h after injury, respectively. The 300 ppm group progressed to severe (PaO/FiO ≤ 100) ARDS at 18 h after injury. Increases in pPeak and pPlateau were noted in all injured animals. Compared to sham, inhalation of 200 ppm and 300 ppm Cl significantly increased lung extravascular water content. The thoracic cavity fluid accumulation dose-dependently increased with the severity of trauma as compared to sham. At necropsy, the lungs were red, heavy, solidified, and fluid filled; the injury severity grew with increasing Cl concentration. The severity of ARDS and mortality rate directly correlated to inhaled Cl concentrations. No significant sex-dependent differences were found in measured endpoint variables.
Topics: Male; Female; Animals; Sheep; Chlorine; Lung; Administration, Inhalation; Respiratory Distress Syndrome
PubMed: 38102196
DOI: 10.1038/s41598-023-48720-2 -
Muscle & Nerve Oct 2023The periodic paralyses are muscle channelopathies: hypokalemic periodic paralysis (CACNA1S and SCN4A variants), hyperkalemic periodic paralysis (SCN4A variants), and...
INTRODUCTION/AIMS
The periodic paralyses are muscle channelopathies: hypokalemic periodic paralysis (CACNA1S and SCN4A variants), hyperkalemic periodic paralysis (SCN4A variants), and Andersen-Tawil syndrome (KCNJ2). Both episodic weakness and disabling fixed weakness can occur. Little literature exists on magnetic resonance imaging (MRI) in muscle channelopathies. We undertake muscle MRI across all subsets of periodic paralysis and correlate with clinical features.
METHODS
A total of 45 participants and eight healthy controls were enrolled and underwent T1-weighted and short-tau-inversion-recovery (STIR) MRI imaging of leg muscles. Muscles were scored using the modified Mercuri Scale.
RESULTS
A total of 17 patients had CACNA1S variants, 16 SCN4A, and 12 KCNJ2. Thirty-one (69%) had weakness, and 9 (20%) required a gait-aid/wheelchair. A total of 78% of patients had intramuscular fat accumulation on MRI. Patients with SCN4A variants were most severely affected. In SCN4A, the anterior thigh and posterior calf were more affected, in contrast to the posterior thigh and posterior calf in KCNJ2. We identified a pattern of peri-tendinous STIR hyperintensity in nine patients. There were moderate correlations between Mercuri, STIR scores, and age. Intramuscular fat accumulation was seen in seven patients with no fixed weakness.
DISCUSSION
We demonstrate a significant burden of disease in patients with periodic paralyses. MRI intramuscular fat accumulation may be helpful in detecting early muscle involvement, particularly in those without fixed weakness. Longitudinal studies are needed to assess the role of muscle MRI in quantifying disease progression over time and as a potential biomarker in clinical trials.
Topics: Humans; Channelopathies; Paralyses, Familial Periodic; Hypokalemic Periodic Paralysis; Muscle, Skeletal; Muscular Dystrophies; Magnetic Resonance Imaging; Paralysis; NAV1.4 Voltage-Gated Sodium Channel; Mutation
PubMed: 37515374
DOI: 10.1002/mus.27947 -
Infection Jun 2024To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome).
PURPOSE
To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome).
METHODS
Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020.
RESULTS
Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27-43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31-514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%).
CONCLUSIONS
Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.
Topics: Humans; Denmark; Female; Adult; Male; Radiculopathy; Cohort Studies; Urinary Retention; Herpesvirus 2, Human; Middle Aged; Lumbosacral Region; Herpes Zoster; Herpesvirus 3, Human
PubMed: 37917395
DOI: 10.1007/s15010-023-02113-9 -
AIDS (London, England) Oct 2023AIDS-defining illness develops at higher CD4 + T-cell counts in individuals infected with HIV-2 compared with HIV-1-infected, which suggests that the two types of HIV...
OBJECTIVE
AIDS-defining illness develops at higher CD4 + T-cell counts in individuals infected with HIV-2 compared with HIV-1-infected, which suggests that the two types of HIV may have different effects on other compartments of the immune system. We here investigate monocyte phenotype, activation and macrophage-derived extracellular vesicles in individuals with different HIV types.
DESIGN
Cross-sectional.
METHODS
ART-naive HIV-1 ( n = 83), HIV-2 ( n = 63), and HIV-1/2 dually positive ( n = 27) participants were recruited in Bissau, Guinea-Bissau, together with HIV-negative controls ( n = 26). Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed by flow cytometry for monocyte phenotype and activation, and plasma was analyzed for extracellular vesicle forms of CD163 and CD206.
RESULTS
Compared with HIV-negative controls, all groups of HIV-positive participants had a skewed monocyte phenotype with a higher proportion of intermediate monocytes, increased CD163 expression and elevated serum levels of the inflammatory biomarkers soluble (s)CD163 and sCD206. HIV-2-positive participants had lower CD163 monocyte expression than HIV-1-positive participants, regardless of HIV RNA or CD4 + cell count. Levels of sCD206 extracellular vesicles were increased in all HIV groups, and higher in HIV-1 compared with HIV-2-positive participants.
CONCLUSION
The monocyte phenotype of HIV-2-positive participants deviated less from healthy controls than did HIV-1 participants. HIV-2-positive participants also had a lower concentration of extracellular CD206 vesicles compared with HIV-1-positive participants. This does not explain the difference in AIDS development.
Topics: Humans; Monocytes; HIV-1; HIV-2; Leukocytes, Mononuclear; Acquired Immunodeficiency Syndrome; HIV Infections; Cross-Sectional Studies; Biomarkers; HIV Seropositivity; Phenotype
PubMed: 37475710
DOI: 10.1097/QAD.0000000000003660 -
MedRxiv : the Preprint Server For... Dec 2023Infants with complex congenital heart disease (CHD) require life-saving corrective/palliative heart surgery in the first weeks of life. These infants are at risk for...
BACKGROUND
Infants with complex congenital heart disease (CHD) require life-saving corrective/palliative heart surgery in the first weeks of life. These infants are at risk for brain injury and poor neurodevelopmental outcomes. Cerebral microhemorrhages (CMH) are frequently seen after neonatal bypass heart surgery, but it remains unknown if CMH are a benign finding or constitute injury. Herein, we investigate the risk factors for developing CMH and their clinical significance.
METHODS
192 infants with CHD undergoing corrective cardiac surgery with cardiopulmonary bypass (CPB) at a single institution were prospectively evaluated with pre-(n = 183) and/or postoperative (n = 162) brain magnetic resonance imaging (MRI). CMH severity was scored based on total number of microhemorrhages. Antenatal, perioperative, and postoperative candidate risk factors for CMH and neurodevelopmental (ND) outcomes were analyzed. Eighteen-month neurodevelopmental outcomes were assessed using the Bayley-III Scales of Infants and Toddler Development in a subset of patients (n = 82). Linear regression was used to analyze associations between risk factors or ND outcomes and presence/number of CMH.
RESULTS
The most common CHD subtypes were hypoplastic left heart syndrome (HLHS) (37%) and transposition of the great arteries (TGA) (33%). Forty-two infants (23%) had CMH present on MRI before surgery and 137 infants (85%) post-surgery. No parameters evaluated were significant risk factors for preoperative CMH. In multivariate analysis, cardiopulmonary bypass (CPB) duration (p < 0.0001), use of extracorporeal membrane oxygenation (ECMO) support (p < 0.0005), postoperative seizure(s) (p < 0.03), and lower birth weight (p < 0.03) were associated with new or worsened CMH postoperatively. Higher CMH number was associated with lower scores on motor (p < 0.03) testing at 18 months.
CONCLUSION
CMH is a common imaging finding in infants with CHD with increased prevalence and severity after CPB and adverse impact on neurodevelopmental outcomes starting at a young age. Longer duration of CPB and need for postoperative ECMO were the most significant risk factors for developing CMH. However, presence of CMH on preoperative scans indicates non-surgical risk factors that are yet to be identified. Neuroprotective strategies to mitigate risk factors for CMH may improve neurodevelopmental outcomes in this vulnerable population.
PubMed: 38105980
DOI: 10.1101/2023.12.05.23299539 -
Research Report (Health Effects... Nov 2023Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective...
INTRODUCTION
Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2.
METHODS
We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO), particulate matter with an aerodynamic diameter <2.5 μm (PM), black carbon (BC), and ozone (O) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES.
RESULTS
Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-μg/m increase in PM and 1.18 (CI: 1.14-1.23) per 3.6-μg/m increase in NO. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO. We also found strong positive and statistically significant associations with BC and negative associations with O. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-μg/m increase in PM and 1.06 (CI: 1.01-1.12) per 3.6-μg/m increase in NO, but no association with PM with an aerodynamic diameter <10 μm (PM), BC, or O and no association between any of the pollutants and COVID-19 mortality (N = 2,557).
CONCLUSIONS
This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.
Topics: Humans; Aged; Nitrogen Dioxide; Prospective Studies; Neurodegenerative Diseases; Environmental Exposure; COVID-19; SARS-CoV-2; Air Pollution; Air Pollutants; Particulate Matter; Cardiovascular Diseases; Incidence; Lung Neoplasms; Denmark
PubMed: 38286761
DOI: No ID Found -
The Ocular Surface Jan 2024This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) for the treatment of dry eye disease (DED) secondary to Sjögren's syndrome (SS).
METHODS
Fifty-four participants with severe DED secondary to SS were included and allocated to either ASCs (n = 20), vehicle (n = 20), or a non-randomized observation group (n = 14). The intervention groups received a single injection of either ASCs or an active comparator (vehicle, Cryostor® CS10) into the LG in one eye, while the observation group received lubricating eye drops only. The primary outcome measure was changes in Ocular Surface Disease Index (OSDI) score and secondary outcome measures were non-invasive tear break-up time, tear meniscus height, Schirmer's test, and Oxford score within a 12-month follow-up.
RESULTS
A significant reduction in OSDI score was observed in the ASCs and vehicle groups compared to the observation group. In addition, the ASCs group demonstrated a significant increase in non-invasive tear break-up time compared to the vehicle group at the 4-week follow-up and to the observation group at the 12-month follow-up. A significant improvement in ocular surface staining, tear osmolarity, and Schirmer test score from baseline was also observed in the ASCs group; however, these changes were not significant compared to the other groups.
CONCLUSION
Improvement of subjective and objective signs and symptoms of DED was observed in both intervention groups following injection into the LG compared to the observation group. Future studies should investigate the mode-of-action of both injection treatments.
Topics: Humans; Sjogren's Syndrome; Mesenchymal Stem Cell Transplantation; Dry Eye Syndromes; Tears; Hematopoietic Stem Cell Transplantation
PubMed: 38049032
DOI: 10.1016/j.jtos.2023.11.007 -
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 -
Acta Anaesthesiologica Scandinavica Nov 2023When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.
METHODS
We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.
RESULTS
The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.
CONCLUSIONS
The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
Topics: Adult; Humans; Respiratory Insufficiency; Respiration, Artificial; Lung; Intensive Care Units; Respiration
PubMed: 37737652
DOI: 10.1111/aas.14317