Takotsubo cardiomyopathy secondary to electroconvulsive therapy in a young adult with Down syndrome regression disorder.

We report the case of an 18-year-old woman with Down syndrome (DS) who developed Takotsubo cardiomyopathy (TSC) immediately after the administration of electroconvulsive therapy (ECT), a treatment prescribed for Down syndrome regression disorder resistant to oral psychotropic drugs. TSC is a nonischemic cardiomyopathy related to psychological or physical stress, which has been described as a rare complication of ECT (Kinoshita et al., 2023, Journal of Electroconvulsive Therapy, 39, 185-192). The clinical description of the case is accompanied by a discussion of the peculiarities of the autonomic nervous system in DS.

Analysis of the circumstances associated with death and predictors of mortality in Spanish adults with Down syndrome, 1997-2014.

OBJECTIVES: Characterise the circumstances associated with death during admission of adults with Down syndrome (DS) and to identify predictors of mortality. PATIENTS AND METHODS: Observational study based on data on all emergent admissions of adults with DS to hospitals of the Spanish National Health System between 1997 and 2014. We analysed epidemiological and clinical variables. RESULTS: We analysed admissions of 11,594 adults with DS, mean age 47 years. 1715 patients died (15%), being the highest mortality (35%) in individuals aged 50-59. A past medical history of cerebrovascular disease (aOR 2.95 [2.30-3.77]) or cancer (aOR 2.79 [2.07-3.75]), gross aspiration's admission (aOR 2.59 [2.20-3.04]), immobility (aOR 2.31 [1.46-3-62]), and readmission within 30 days (aOR 2.43 [2.06-2.86]) were identified as predictors of mortality. CONCLUSIONS: Adults with DS have a high in-hospital mortality rate. The main predictors of death were cerebrovascular disease, cancer, early readmission, and conditions commonly associated with advanced dementia.

Animating Clinical Ethics: A Structured Method to Teach Ethical Analysis Through Movies.

Movies can serve valuable didactic purposes teaching clinical ethics to medical students. However, using film sequences as means to develop critical thinking is not a straightforward task. There is a significant gap in the literature regarding how to analyse the ethical content embedded in these clips systematically, in a way that facilitates the students' transition from anecdotal reflections to abstract thinking. This article offers a pedagogical proposal to approach the ethical analysis of film sequences in a systematic fashion. This structured stepwise method encourages students to identify the main ethical problem of a selected scene and to reflect on the theoretical principles involved, emphasizing the application of these norms and values in a contextually situated analysis. We believe this method in film studies both reinforces the students' comprehension of the theoretical framework of an ethical topic, and casts light on its pertinence and limitations under the circumstances of the scene, thus proving a constructive tool to strengthen the bridge between the theoretical teaching of clinical ethics and clinical practice.

Volumetric BMD by 3D-DXA and Trabecular Bone Score in Adults With Down Syndrome.

Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm3 vs 206.9 ± 46.7 mg/cm3, p = 0.007, and 250.5 ± 70.1 mg/cm3 vs 275.7 ± 66.2 mg/cm3, p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects.

Bone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome.

According to reports from small-sized case series, adults with Down syndrome (DS) appear to have lower bone mineral density (BMD) than the general population. The objective of our study was to further characterize the bone mass acquisition curve in an adult DS population. This is a retrospective study of 297 adults with DS from the Adult Down Syndrome Outpatient Clinic of a tertiary care hospital in Madrid, Spain, who underwent a bone densitometry (Hologic QDR-4500W), for clinical purposes between January 2010 and June 2015. The mean age of our sample population was 34 yr (±10.9); 51% were women. Bone mass peak was reached earlier and was lower than the general population (around 20-25 yr), with almost parallel curves. The mean BMD was 0.715 ± 0.12 g/cm2 in femoral neck (FN) and 0.872 ± 0.11 g/cm2 in lumbar spine (LS). According to FN scores, 52% of the subjects were classified as osteopenic and 18% as osteoporotic. According to LS scores, frequencies were 54% and 25%, respectively. BMD was considered inadequate for the age (Z-score < -2 standard deviation) in 18% of the subjects at FN and 40% at LS. BMD at LS was significantly lower in males than in females (52% vs 38%, p < 0.001). Male DS subjects had a 2.58-fold (95% confidence interval: 1.57-4.25) higher risk of developing reduced BMD at LS than females. Persons with DS reach the bone mass peak earlier and this bone mass is lower than the general population. Among subjects with DS, male gender is a risk factor for developing low BMD, especially at LS.

Off the Charts: Medical documentation and selective redaction in the age of transparency.

A growing demand for transparency in medicine has the potential to strain the doctor-patient relationship. While information can empower patients, unrestricted patient access to the electronic medical record may have unintended consequences. Medical documentation is often written in language that is inaccessible to people without medical training, and without guidance, patients have no way to interpret the constellation of acronyms, diagnoses, treatments, impressions, and arguments that appear throughout their own chart. Additionally, full transparency may not allow physicians the intellectual or clinical freedom they need to authentically express questions, problematic impressions, and concerns about the patient's clinical and psychosocial issues. This article examines the ethical challenges of transparency in the digital era and suggests that selective redaction may serve as a means to maintain transparency, affirm physician's discretion, and uphold the core values of the doctor-patient relationship amidst disruptive technological change.

Voxel-based dysconnectomic brain morphometry with computed tomography in Down syndrome.

OBJECTIVE: Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort. METHODS: CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated. RESULTS: Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri. INTERPRETATION: Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain.

De novo variants in immune regulatory genes in Down syndrome regression disorder.

BACKGROUND: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD. METHODS: This study included individuals with DSRD aged 10-30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher's exact test) were used to describe and compare the characteristics of individuals with and without variants. RESULTS: Forty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic (UNC13D, XIAP, RNASEH2A, and DNASE1L3). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger (p = 0.03, 95% CI 1.21-97.06), rapid clinical decline in less than 1 month (p = 0.01, 95% CI 1.67-52.06), and MRI abnormalities (p < 0.001, 95% CI 4.89-527.71). DISCUSSION: A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS.

Medical vulnerability of individuals with Down syndrome to severe COVID-19-data from the Trisomy 21 Research Society and the UK ISARIC4C survey.

BACKGROUND: Health conditions, immune dysfunction, and premature aging associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19. METHODS: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers on patients with COVID-19 and DS. Data collected between April and October 2020 (N=1046) were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. FINDINGS: The mean age of COVID-19 patients with DS in the T21RS survey was 29 years (SD = 18). Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Joint/muscle pain and vomiting or nausea were less frequent (p < 0.01), whereas altered consciousness/confusion were more frequent (p < 0.01). Risk factors for hospitalization and mortality were similar to the general population with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher in patients with DS (T21RS DS versus non-DS patients: risk ratio (RR) = 3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus non-DS patients: RR = 2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. INTERPRETATION: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of medical complications and mortality, especially from age 40. FUNDING: Down Syndrome Affiliates in Action, DSMIG-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, The Matthew Foundation, NDSS, National Task Group on Intellectual Disabilities and Dementia Practices.

An international survey on the impact of COVID-19 in individuals with Down syndrome.

BACKGROUND: Health conditions and immune dysfunction associated with trisomy 21 (Down syndrome, DS) may impact the clinical course of COVID-19 once infected by SARS-CoV-2. METHODS: The T21RS COVID-19 Initiative launched an international survey for clinicians or caregivers/family members on patients with COVID-19 and DS (N=1046). De-identified survey data collected between April and October 2020 were analysed and compared with the UK ISARIC4C survey of hospitalized COVID-19 patients with and without DS. COVID-19 patients with DS from the ISARIC4C survey (ISARIC4C DS cases=100) were matched to a random set of patients without DS (ISARIC4C controls=400) and hospitalized DS cases in the T21RS survey (T21RS DS cases=100) based on age, gender, and ethnicity. FINDING: The mean age in the T21RS survey was 29 years (SD=18), 73% lived with their family. Similar to the general population, the most frequent signs and symptoms of COVID-19 were fever, cough, and shortness of breath. Pain and nausea were reported less frequently (p<0.01), whereas altered consciousness/confusion were reported more frequently (p<0.01). Risk factors for hospitalization and mortality were similar to the general population (age, male gender, diabetes, obesity, dementia) with the addition of congenital heart defects as a risk factor for hospitalization. Mortality rates showed a rapid increase from age 40 and were higher than for controls (T21RS DS versus controls: risk ratio (RR)=3.5 (95%-CI=2.6;4.4), ISARIC4C DS versus controls: RR=2.9 (95%-CI=2.1;3.8)) even after adjusting for known risk factors for COVID-19 mortality. INTERPRETATION: Leading signs/symptoms of COVID-19 and risk factors for severe disease course are similar to the general population. However, individuals with DS present significantly higher rates of mortality, especially from age 40. FUNDING: Down Syndrome Affiliates in Action, Down Syndrome Medical Interest Group-USA, GiGi's Playhouse, Jerome Lejeune Foundation, LuMind IDSC Foundation, Matthews Foundation, National Down Syndrome Society, National Task Group on Intellectual Disabilities and Dementia Practices.

Frequency of Ethical Issues on a Hospitalist Teaching Service at an Urban, Tertiary Care Center.

Little is known about the daily ethical conflicts encountered by hospitalists that do not prompt a formal clinical ethics consultation. We describe the frequencies of ethical issues identified during daily rounds on hospitalist teaching services at a metropolitan, tertiary-care, teaching hospital. Data were collected from September 2017 through May 2018 by two attending hospitalists from the ethics committee who were embedded on rounds. A total of 270 patients were evaluated and 113 ethical issues were identified in 77 of those patients. These issues most frequently involved discussions about goals of care, treatment refusals, decision-making capacity, discharge planning, cardiopulmonary resuscitation status, and pain management. Only five formal consults were brought to the Hospital Ethics Committee for these 270 patients. Our data are the first prospective description of ethical issues arising on academic hospitalist teaching services and are an important step in the development of a targeted ethics curriculum for hospitalists.

Atherosclerotic Surrogate Markers in Adults With Down Syndrome: A Case-Control Study.

The authors aimed to compare surrogate markers of atherosclerosis (pulse wave velocity, intima-media thickness) between adults with and without Down syndrome (DS) and to assess the impact of parathyroid hormone levels and classic cardiovascular risk factors on arterial stiffness. After comparing 51 adults with DS and 51 healthy adults (siblings of DS individuals), the authors found that adults with DS seem to have lower arterial stiffness, as a result of chronic hypotension. Subclinical atherosclerosis parameters do not correlate with traditional cardiovascular risk factors in adults with DS, thus raising the hypothesis that classic predictive models for cardiovascular disease are not valid in this population. Hyperparathyroidism could play an important role in arterial damage in these individuals. The lower than expected prevalence of obesity and dyslipidemia could be explained by better eating habits, with this study being the first to address the anthropometric and clinical profile of a Mediterranean cohort of adults with DS.

Bone Mass Assessment in a Cohort of Adults With Down Syndrome: A Cross-Sectional Study.

Differences in bone mineral density (BMD) have been observed between adults with Down syndrome (DS) and the general population. The purpose of this article is to describe the prevalence of bone mass disorders in a cohort of adults with DS and their predisposing factors. We performed a cross-sectional study of 104 consecutively recruited adults with DS from an outpatient clinic of a tertiary care hospital in Madrid, Spain. We recorded epidemiological and anthropometric data, nutritional variables, coexisting clinical conditions, and laboratory variables. BMD was measured at the lumbar spine, total hip, and femoral neck using dual-energy X-ray absorptiometry. The prevalence of osteopenia ranged from 48% to 52%, and that of osteoporosis ranged from 19% to 22% depending on the site of measurement (femoral neck or lumbar spine, respectively). Age was the greatest risk factor associated for lower BMD, with similar bone mass accrual curve but with lower peak of BMD than the general population. We conclude that low bone mass is an extremely prevalent condition in adult patients with DS.