-
Medicina Clinica Mar 2024
Topics: Humans; Andersen Syndrome; Long QT Syndrome; Mutation
PubMed: 38044185
DOI: 10.1016/j.medcli.2023.10.021 -
The Journal of Pediatric Pharmacology... 2023We present a case of bidirectional ventricular tachycardia in a 15-year-old boy asymptomatic for arrhythmias, whose major complaint was muscle weakness. At our first...
We present a case of bidirectional ventricular tachycardia in a 15-year-old boy asymptomatic for arrhythmias, whose major complaint was muscle weakness. At our first evaluation he was receiving sotalol for his ventricular arrhythmias. In addition to bidirectional tachycardia, electrocardiogram during sinus rhythm showed prominent U waves and prolonged QT-U interval. These electrocardiographic signs, along with the evidence of clinodactyly and mild hypertelorism, led us to the diagnosis of Andersen-Tawil syndrome, confirmed by genetic analysis that revealed a "" missense mutation of KCNJ2 gene. Monotherapy with flecainide was rapidly effective and almost eliminated ventricular arrhythmias. After a 4-year follow-up there were no adverse events, flecainide has been well tolerated without significant modification of the QRS or repolarization, and ventricular arrhythmias have not been relapsed to date. The case highlights the importance of a correct clinical diagnosis, which is crucial for the optimal selection of the most appropriate drug therapy, which is expected not to be harmful, before being beneficial.
PubMed: 38025154
DOI: 10.5863/1551-6776-28.7.662 -
Therapeutic Advances in... 2023Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in...
BACKGROUND
Severe mental illness (SMI) is associated with increased cardiovascular risk. Dyslipidaemia is a potentially modifiable risk factor, which may be inadequately managed in patients with SMI.
OBJECTIVES
To assess management of dyslipidaemia in patients with SMI healthy controls (HCs) in 2005 and 2015.
DESIGN AND METHODS
Using Danish registers, we identified adult patients with SMI in the Greater Copenhagen Area (schizophrenia spectrum disorders or bipolar disorder) with ⩾1 general practitioner contact in the year before 2005 and 2015, respectively, and HCs without SMI matched on age and gender (1:5). Outcomes were lipid-profile measurements, presence of dyslipidaemia and redemption of lipid-lowering pharmacotherapy. Differences in outcomes between patients with SMI and controls were measured with multivariable logistic regression.
RESULTS
We identified 7217 patients with SMI in 2005 and 9939 in 2015. After 10 years, patients went from having lower odds of lipid measurements to having higher odds of lipid measurements compared with HCs [odds ratio (OR) 0.70 (99% confidence interval (CI) 0.63-0.78) OR 1.34 (99% CI 1.24-1.44); < 0.01]. Patients had higher odds of dyslipidaemia during both years [OR 1.43 (99% CI 1.10-1.85) and OR 1.23 (99% CI 1.08-1.41)]. Patients went from having lower odds of receiving lipid-lowering pharmacotherapy to having higher odds of receiving lipid-lowering pharmacotherapy [OR 0.77 (99% CI 0.66-0.89) OR 1.37 (99% CI 1.24-1.51); < 0.01]. However, among persons at high cardiovascular risk, patients had lower odds of receiving lipid-lowering pharmacotherapy during both years, including subsets with previous acute coronary syndrome [OR 0.30 (99% CI 0.15-0.59) and OR 0.44 (99% CI 0.24-0.83)] and ischaemic stroke or transient ischaemic attack (TIA) [OR 0.43 (99% CI 0.26-0.69) and OR 0.61 (99% CI 0.41-0.89)].
CONCLUSION
These results imply an increased general awareness of managing dyslipidaemia among patients with SMI in the primary prophylaxis of cardiovascular disease. However, secondary prevention with lipid-lowering drugs in patients with SMI at high cardiovascular risk may be lacking.
PubMed: 38022836
DOI: 10.1177/20451253231211574 -
Ugeskrift For Laeger Nov 2023Rusty pipe syndrome (RPS) is a benign, self-limiting condition characterized by bloody milk secretion, and is primarily seen among primiparous women. This case report...
Rusty pipe syndrome (RPS) is a benign, self-limiting condition characterized by bloody milk secretion, and is primarily seen among primiparous women. This case report highlights the clinical presentation of a 31-year-old primiparous woman with bloody milk secretion from gestational week 31. This persisted throughout pregnancy until seven days after birth. RPS should be considered in pregnant women with painless bilateral bloody milk secretion during pregnancy and/or the early days post-partum. The milk can safely be provided to the infant, and RPS is not an indication for formula feeding.
Topics: Infant; Female; Pregnancy; Humans; Adult; Animals; Breast Feeding; Lactation; Milk; Postpartum Period; Syndrome; Parity
PubMed: 38018741
DOI: No ID Found -
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 -
Therapeutic Hypothermia and Temperature... Nov 2023Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen...
Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. This study investigated serial levels of suPAR in differentiated target temperature management and the associations with mortality and 6-month neurological outcome. This is a single-center substudy of the randomized Targeted Temperature Management (TTM) for 24-hour versus 48-hour trial. In this analysis, we included 82 patients and measured serial levels of suPAR at 24, 48, and 72 hours after achievement of target temperature (32-34°C). We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories (CPC) at 6 months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method and serial measurements of suPAR (log transformed) were investigated by Cox proportional-hazards models. Good neurological outcome at 6 months was assessed by logistic regression analyses. Levels of suPAR were significantly different between TTH groups (p = 0.04) with the highest difference at 48 hours, 4.7 ng/mL (95% CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95% CI: 2.2-3.5 ng/mL) in the TTH48 group, < 0.0001. Levels of suPAR above the median value were significantly associated with increased all-cause mortality at any time point (p<0.05). The interaction of suPAR levels and TTH group was not significant (p = NS). A twofold increase in levels of suPAR was significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (p = NS). Prolonged TTM of 48 hours versus 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at 6 months with no significant interaction of TTH group.
PubMed: 37910781
DOI: 10.1089/ther.2023.0039 -
Frontiers in Endocrinology 2023Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including...
BACKGROUND
Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O).
METHODS
Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated.
RESULTS
Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events.
CONCLUSION
Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.
Topics: Humans; Female; Bone Marrow; Glucocorticoids; Cushing Syndrome; Adiposity; Postmenopause; Hyperplasia; Hydrocortisone; Osteoporosis, Postmenopausal; Osteoporosis; Hypertrophy
PubMed: 37881495
DOI: 10.3389/fendo.2023.1232574 -
Toxicology and Applied Pharmacology Nov 2023The use and/or misuse of opioids by pregnant women would expose the fetuses to these drugs during critical stages of development with serious effects for the newborn,...
The use and/or misuse of opioids by pregnant women would expose the fetuses to these drugs during critical stages of development with serious effects for the newborn, like the neonatal abstinence syndrome (NAS). We have revisited an established chicken model for NAS to describe the distribution of morphine and methadone to the brain and explore its validity as a valuable alternative to rodent models. For this purpose, chicken eggs were injected with a single dose of 10 mg/kg or 20 mg/kg morphine or 20 mg/kg methadone onto the chorioallantoic membrane (CAM) on embryonal day 13. Whole brains and lungs were harvested and the concentrations of morphine, methadone and their subsequent metabolites (morphine-3-glucuronide and EDDP, respectively) determined in the brain and lungs at different time points using LC-MS/MS. Morphine and methadone, as well as their metabolites, were detected both in the brain and lungs, with significantly higher concentrations in the lungs. Pharmacokinetic modelling showed that the distribution of morphine to the brain followed a first-order absorption with transit compartments and linear elimination, with concentrations linearly dependent on dose. Moreover, methadone, but not morphine, reduced μ receptor (the main morphine receptor) binding, which can be of relevance for opioid tolerance. The present study is the first to report the brain distribution of morphine, which can be described by standard pharmacokinetic processes, and methadone in the developing chicken embryo. The present findings supplement the already established model and support the use of this chicken model to study NAS.
Topics: Chick Embryo; Infant, Newborn; Animals; Female; Pregnancy; Humans; Methadone; Morphine; Analgesics, Opioid; Chickens; Chromatography, Liquid; Drug Tolerance; Tandem Mass Spectrometry; Neonatal Abstinence Syndrome; Brain; Receptors, Opioid, mu
PubMed: 37866706
DOI: 10.1016/j.taap.2023.116731 -
Journal of the Intensive Care Society Nov 2023The aim of this study was to assess the feasibility and outcome of a neuropsychiatric evaluation protocol intended for adult intensive care unit survivors in a Danish...
The aim of this study was to assess the feasibility and outcome of a neuropsychiatric evaluation protocol intended for adult intensive care unit survivors in a Danish regional hospital, in which a follow-up consultation was conducted 2 months after hospital discharge. Twenty-three participants were able to finalize the neuropsychiatric evaluation, and 20 (87%) among those were detected with neuropsychiatric manifestations, including cognitive impairment ( = 17; 74%) and fatigue ( = 17, 74%). This study finds a high prevalence of neuropsychiatric manifestations and fatigue, and evaluates a follow-up protocol for the ICU patient population.
PubMed: 37841303
DOI: 10.1177/17511437231151527 -
Annals of the Rheumatic Diseases Jan 2024To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.
OBJECTIVES
To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.
METHODS
An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.
RESULTS
The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.
CONCLUSION
The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.
Topics: Humans; Azathioprine; Tacrolimus; Rituximab; Methotrexate; Lupus Erythematosus, Systemic; Immunosuppressive Agents; Cyclophosphamide; Hydroxychloroquine; Glucocorticoids; Enzyme Inhibitors
PubMed: 37827694
DOI: 10.1136/ard-2023-224762