Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering the pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator's area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including aetiology-specific aspects and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before the expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable.
- MeSH
- Action Potentials MeSH
- Cardiology * standards MeSH
- Tachycardia, Ventricular * physiopathology surgery diagnosis MeSH
- Consensus MeSH
- Humans MeSH
- Radiosurgery * adverse effects standards methods MeSH
- Risk Factors MeSH
- Patient Selection * MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Practice Guideline MeSH
- Geographicals
- Europe MeSH
IMPORTANCE: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. OBJECTIVE: To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. MAIN OUTCOMES AND MEASURES: Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. RESULTS: In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. CONCLUSIONS AND RELEVANCE: Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.
- MeSH
- Amyloid beta-Peptides * cerebrospinal fluid metabolism MeSH
- Apolipoprotein E4 genetics MeSH
- Biomarkers cerebrospinal fluid MeSH
- Depression * MeSH
- Adult MeSH
- Cognitive Dysfunction * MeSH
- Middle Aged MeSH
- Humans MeSH
- Peptide Fragments cerebrospinal fluid MeSH
- Positron-Emission Tomography * MeSH
- Cross-Sectional Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Age Factors MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Lithium is the gold standard prophylactic treatment for bipolar disorder. Most clinical practice guidelines recommend regular calcium assessments as part of monitoring lithium treatment, but easy-to-implement specific management strategies in the event of abnormal calcium levels are lacking. METHODS: Based on a narrative review of the effects of lithium on calcium and parathyroid hormone (PTH) homeostasis and its clinical implications, experts developed a step-by-step algorithm to guide the initial management of emergent hypercalcemia during lithium treatment. RESULTS: In the event of albumin-corrected plasma calcium levels above the upper limit, PTH and calcium levels should be measured after two weeks. Measurement of PTH and calcium levels should preferably be repeated after one month in case of normal or high PTH level, and after one week in case of low PTH level, independently of calcium levels. Calcium levels above 2.8 mmol/l may require a more acute approach. If PTH and calcium levels are normalized, repeated measurements are suggested after six months. In case of persistent PTH and calcium abnormalities, referral to an endocrinologist is suggested since further examination may be needed. CONCLUSIONS: Standardized consensus driven management may diminish the potential risk of clinicians avoiding the use of lithium because of uncertainties about managing side-effects and consequently hindering some patients from receiving an optimal treatment.
- Publication type
- Journal Article MeSH
AIM: To date, there is a lack of international guidelines regarding the management of the endocrine features of individuals with Noonan syndrome (NS). The aim was to develop a clinical practice survey to gather information on current treatment and management of these patients across Europe. MATERIALS AND METHODS: A group of 10 experts from three clinical specialities involved in the management of NS patients (clinical geneticists, paediatric endocrinologists, and paediatric cardiologists) developed a 60-question clinical practice survey. The questionnaire was implemented in Survey Monkey and sent to physicians from these three specialities via European/national societies. Contingency tables and the Chi-Squared test for independence were used to examine differences between specialities and countries. RESULTS: In total, responses of 364 specialists (paediatric endocrinologists, 40%; geneticists, 30%; paediatric cardiologists, 30%) from 20 European countries were analysed. While endocrinologists mostly referred to national growth charts for the general population, geneticists mostly referred to NS-specific growth charts. Approximately half of the endocrinologists perform growth hormone (GH) stimulation tests in short patients with low IGF1 levels. Two thirds of endocrinologists begin GH treatment for short patients in early childhood (4-6.9 years), and over half of them selected a threshold of -2 standard deviation score (SDS) according to national growth charts. The main concerns about GH treatment appear to be presence of hypertrophic cardiomyopathy (HCM) (59%), increased risk of malignancy (46%), and limited efficacy (31%). When asked if they consider HCM as a contraindication for GH treatment, one third of respondents skipped this question, and among those who replied, two thirds selected 'cannot answer', suggesting a high level of uncertainty. A total of 21 adverse cardiac responses to GH treatment were reported. Although most respondents had not encountered any malignancy during GH treatment, six malignancies were reported. Finally, about half of the endocrinologists expected a typical final height gain of 1-1.5 SDS with GH treatment. CONCLUSION: This survey describes for the first time the current clinical practice of endocrine aspects of NS across Europe and helps us to identify gaps in the management but also in the knowledge of this genetic disorder.
- MeSH
- Endocrinologists MeSH
- Practice Patterns, Physicians' MeSH
- Humans MeSH
- Human Growth Hormone therapeutic use MeSH
- Dwarfism diagnosis drug therapy MeSH
- Noonan Syndrome diagnosis drug therapy MeSH
- Surveys and Questionnaires MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
BACKGROUND: The majority of children with Noonan syndrome (NS) or other diseases from the RASopathy spectrum suffer from congenital heart disease. This study aims to survey cardiac care of this patient cohort within Europe. METHODS: A cross-sectional exploratory survey assessing the treatment and management of patients with NS by paediatric endocrinologists, cardiologists and clinical geneticists was developed. This report details responses of 110 participating paediatric cardiologists from multiple countries. RESULTS: Most paediatric cardiologists responding to the questionnaire were associated with university hospitals, and most treated <10 patients/year with congenital heart disease associated with the NS spectrum. Molecular genetic testing for diagnosis confirmation was initiated by 81%. Half of the respondents reported that patients with NS and congenital heart disease typically present <1y of age, and that a large percentage of affected patients require interventions and pharmacotherapy early in life. A higher proportion of infant presentation and need for pharmacotherapy was reported by respondents from Germany and Sweden than from France and Spain (p = 0.031; p = 0.014; Fisher's exact test). Older age at first presentation was reported more from general hospitals and independent practices than from university hospitals (p = 0.031). The majority of NS patients were followed at specialist centres, but only 37% reported that their institution offered dedicated transition clinic to adult services. Very few NS patients with hypertrophic cardiomyopathy (HCM) were reported to carry implantable cardioverter defibrillators for sudden cardiac death prevention. Uncertainty was evident in regard to growth hormone treatment in patients with NS and co-existing HCM, where 13% considered it not a contra-indication, 24% stated they did not know, but 63% considered HCM either a possible (20%) or definite (15%) contraindication, or a cause for frequent monitoring (28%). Regarding adverse reactions for patients with NS on growth hormone therapy, 5/19 paediatric cardiology respondents reported a total of 12 adverse cardiac events. CONCLUSIONS: Congenital heart disease in patients with NS or other RASopathies is associated with significant morbidity during early life, and specialty centre care is appropriate. More research is needed regarding the use of growth hormone in patients with NS with congenital heart disease, and unmet medical needs have been identified.
- MeSH
- Child MeSH
- Genetic Testing MeSH
- Cardiologists MeSH
- Practice Patterns, Physicians' * MeSH
- Humans MeSH
- Human Growth Hormone therapeutic use MeSH
- Noonan Syndrome * complications diagnosis genetics therapy MeSH
- Surveys and Questionnaires MeSH
- Heart Defects, Congenital * diagnosis etiology genetics therapy MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The COVID-19 pandemic is commonly believed to have increased common mental disorders (CMD, i.e., depression and anxiety), either directly due to COVID-19 contractions (death of near ones or residual conditions), or indirectly by increasing stress, economic uncertainty, and disruptions in daily life resulting from containment measure. Whereas studies reporting on initial changes in self-reported data frequently have reported increases in CMD, pandemic related changes in CMD related to primary care utilization are less well known. Analyzing time series of routinely and continuously sampled primary healthcare data from Sweden, Norway, Netherlands, and Latvia, we aimed to characterize the impact of the pandemic on CMD recorded prevalence in primary care. Furthermore, by relating these changes to country specific time-trajectories of two classes of containment measures, we evaluated the differential impact of containment strategies on CMD rates. Specifically, we wanted to test whether school restrictions would preferentially affect age groups corresponding to those of school children or their parents. METHODS: For the four investigated countries, we collected time-series of monthly counts of unique CMD patients in primary healthcare from the year 2015 (or 2017) until 2021. Using pre-pandemic timepoints to train seasonal Auto Regressive Integrated Moving Average (ARIMA) models, we predicted healthcare utilization during the pandemic. Discrepancies between observed and expected time series were quantified to infer pandemic related changes. To evaluate the effects of COVID-19 measures on CMD related primary care utilization, the predicted time series were related to country specific time series of levels of social distancing and school restrictions. RESULTS: In all countries except Latvia there was an initial (April 2020) decrease in CMD care prevalence, where largest drops were found in Sweden (Prevalence Ratio, PR = 0.85; 95% CI 0.81-0.90), followed by Netherlands (0.86; 95% CI 0.76-1.02) and Norway (0.90; 95% CI 0.83-0.98). Latvia on the other hand experienced increased rates (1.25; 95% CI 1.08-1.49). Whereas PRs in Norway and Netherlands normalized during the latter half of 2020, PRs stayed low in Sweden and elevated in Latvia. The overall changes in PR during the pandemic year 2020 was significantly changed only for Sweden (0.91; 95% CI 0.90-0.93) and Latvia (1.20; 95% CI 1.14-1.26). Overall, the relationship between containment measures and CMD care prevalence were weak and non-significant. In particular, we could not observe any relationship of school restriction to CMD care prevalence for the age groups best corresponding to school children or their parents. CONCLUSION: Common mental disorders prevalence in primary care decreased during the initial phase of the COVID-19 pandemic in all countries except from Latvia, but normalized in Norway and Netherlands by the latter half of 2020. The onset of the pandemic and the containment strategies were highly correlated within each country, limiting strong conclusions on whether restriction policy had any effects on mental health. Specifically, we found no evidence of associations between school restrictions and CMD care prevalence. Overall, current results lend no support to the common belief that the pandemic severely impacted the mental health of the general population as indicated by healthcare utilization, apart from in Latvia. However, since healthcare utilization is affected by multiple factors in addition to actual need, future studies should combine complementary types of data to better understand the mental health impacts of the pandemic.
- Publication type
- Journal Article MeSH
An estimated 1.3 million pregnant women were living with HIV in 2018. HIV infection is associated with adverse pregnancy outcomes and all HIV-positive pregnant women, regardless of their clinical stage, should receive a combination of antiretroviral drugs to suppress maternal viral load and prevent vertical fetal infection. Although antiretroviral treatment in pregnant women has undoubtedly minimized mother-to-child transmission of HIV, several uncertainties remain. For example, while pregnancy is accompanied by changes in pharmacokinetic parameters, relevant data from clinical studies are lacking. Similarly, long-term adverse effects of exposure to antiretrovirals on fetuses have not been studied in detail. Here, we review current knowledge on HIV effects on the placenta and developing fetus, recommended antiretroviral regimens, and pharmacokinetic considerations with particular focus on placental transport. We also discuss recent advances in antiretroviral research and potential effects of antiretroviral treatment on placental/fetal development and programming.
- MeSH
- Anti-Retroviral Agents pharmacology MeSH
- HIV Infections drug therapy transmission MeSH
- Pregnancy Complications, Infectious drug therapy virology MeSH
- Humans MeSH
- Placenta virology MeSH
- Pregnancy MeSH
- Infectious Disease Transmission, Vertical prevention & control MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
PURPOSE: Microwave ablation (MWA) is a clinically established modality for treatment of lung tumors. A challenge with existing application of MWA, however, is local tumor progression, potentially due to failure to establish an adequate treatment margin. This study presents a robust simulation-based treatment planning methodology to assist operators in comparatively assessing thermal profiles and likelihood of achieving a specified minimum margin as a function of candidate applied energy parameters. METHODS: We employed a biophysical simulation-based probabilistic treatment planning methodology to evaluate the likelihood of achieving a specified minimum margin for candidate treatment parameters (i.e., applied power and ablation duration for a given applicator position within a tumor). A set of simulations with varying tissue properties was evaluated for each considered combination of power and ablation duration, and for four different scenarios of contrast in tissue biophysical properties between tumor and normal lung. A treatment planning graph was then assembled, where distributions of achieved minimum ablation zone margins and collateral damage volumes can be assessed for candidate applied power and treatment duration combinations. For each chosen power and time combination, the operator can also visualize the histogram of ablation zone boundaries overlaid on the tumor and target volumes. We assembled treatment planning graphs for generic 1, 2, and 2.5 cm diameter spherically shaped tumors and also illustrated the impact of tissue heterogeneity on delivered treatment plans and resulting ablation histograms. Finally, we illustrated the treatment planning methodology on two example patient-specific cases of tumors with irregular shapes. RESULTS: The assembled treatment planning graphs indicate that 30 W, 6 min ablations achieve a 5-mm minimum margin across all simulated cases for 1-cm diameter spherical tumors, and 70 W, 10 min ablations achieve a 3-mm minimum margin across 90% of simulations for a 2.5-cm diameter spherical tumor. Different scenarios of tissue heterogeneity between tumor and lung tissue revealed 2 min overall difference in ablation duration, in order to reliably achieve a 4-mm minimum margin or larger each time for 2-cm diameter spherical tumor. CONCLUSIONS: An approach for simulation-based treatment planning for microwave ablation of lung tumors is illustrated to account for the impact of specific geometry of the treatment site, tissue property uncertainty, and heterogeneity between the tumor and normal lung.
Cardiac troponin T determination plays a dominant role in diagnosis of myocardial pathologies. Despite generally accepted use of high-sensitive cardiac troponin T assays (hscTnT) and clearly defined cut-off limit in adults, the uncertainty persists in infants. The aim of this study was to assess plasmatic concentrations of hscTnT and describe sequential age-related dynamic changes of hscTnT in healthy infants and toddlers. Seventy-eight children (52 males/26 females) from Czech Republic aged 44 to 872 days (median, interquartile range 271; 126 to 486 days) were consecutively enrolled in the single-center, prospective observational study. Plasma concentrations of hscTnT were analyzed by the electrochemiluminescent method, age-related reference intervals were calculated using the polynominal regression model. Amongst the study population (n=78), the upper limit of hscTnT concentration defined as the 99th percentile was calculated. The 99th percentile with 95 % confidence interval at the end of 2nd, 3rd, 4th, 5th, 6th and 7th month of postnatal life were: 81 (40.6 to 63.6), 61 (36.0 to 55.3), 47 (31.9 to 48.3), 37 (28.1 to 42.3), 30 (24.7 to 37.2) and 25 (21.5 to 32.7) ng/l, respectively. Concentration of adults 99th percentile (14 ng/l) was achieved approximately at 1 year of postnatal life. Statistically significant negative correlation of hscTnT concentration with age (r=-0.81, p<0.001) was found. Significant gender differences were not found (p>0.07). The study revealed substantially increased reference intervals of hscTnT levels in infants when compared with adult population. Based on our preliminary results, the age-related interpretation of hscTnT plasmatic concentration is recommended.
- MeSH
- Biomarkers blood MeSH
- Myocardial Infarction blood diagnosis epidemiology MeSH
- Infant MeSH
- Humans MeSH
- Child, Preschool MeSH
- Prospective Studies MeSH
- Reference Values MeSH
- Sex Factors MeSH
- Troponin T blood MeSH
- Age Factors MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Ionizing radiation is a genotoxic anthropogenic stressor. It can cause heritable changes in the plant genome, which can be either adaptive or detrimental. There is still considerable uncertainty about the effects of chronic low-intensity doses since earlier studies reported somewhat contradictory conclusions. Our project focused on the recovery from the multiyear chronic ionizing radiation stress. Soybean (Glycine max) was grown in field plots located at the Chernobyl exclusion zone and transferred to the clean ground in the subsequent generation. We profiled proteome of mature seeds by two-dimensional gel electrophoresis. Overall, 15 differentially abundant protein spots were identified in the field comparison and 11 in the recovery generation, primarily belonging to storage proteins, disease/defense, and metabolism categories. Data suggested that during multigenerational growth in a contaminated environment, detrimental heritable changes were accumulated. Chlorophyll fluorescence parameters were measured on the late vegetative state, pointing to partial recovery of photosynthesis from stress imposed by contaminating radionuclides. A plausible explanation for the observed phenomena is insufficient provisioning of seeds by lower quality resources, causing a persistent effect in the offspring generation. Additionally, we hypothesized that immunity against phytopathogens was compromised in the contaminated field, but perhaps even primed in the clean ground, yet this idea requires direct functional validation in future experiments. Despite showing clear signs of physiological recovery, one season was not enough to normalize biochemical processes. Overall, our data contribute to the more informed agricultural radioprotection.
- MeSH
- Electrophoresis, Gel, Two-Dimensional MeSH
- Chernobyl Nuclear Accident * MeSH
- Stress, Physiological * MeSH
- Glycine max growth & development physiology radiation effects MeSH
- Radiation, Ionizing * MeSH
- Proteome radiation effects MeSH
- Plant Proteins metabolism MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Ukraine MeSH
