Sensory-Processing Sensitivity Is Associated with Increased Neural Entropy.

BACKGROUND: This study aimed at answering the following research questions: (1) Does the self-reported level of sensory-processing sensitivity (SPS) correlate with complexity, or criticality features of the electroencephalogram (EEG)? (2) Are there significant EEG differences comparing individuals with high and low levels of SPS? METHODS: One hundred fifteen participants were measured with 64-channel EEG during a task-free resting state. The data were analyzed using criticality theory tools (detrended fluctuation analysis, neuronal avalanche analysis) and complexity measures (sample entropy, Higuchi's fractal dimension). Correlations with the 'Highly Sensitive Person Scale' (HSPS-G) scores were determined. Then, the cohort's lowest and the highest 30% were contrasted as opposites. EEG features were compared between the two groups by applying a Wilcoxon signed-rank test. RESULTS: During resting with eyes open, HSPS-G scores correlated significantly positively with the sample entropy and Higuchi's fractal dimension (Spearman's ρ = 0.22, p < 0.05). The highly sensitive group revealed higher sample entropy values (1.83 ± 0.10 vs. 1.77 ± 0.13, p = 0.031). The increased sample entropy in the highly sensitive group was most pronounced in the central, temporal, and parietal regions. CONCLUSION: For the first time, neurophysiological complexity features associated with SPS during a task-free resting state were demonstrated. Evidence is provided that neural processes differ between low- and highly-sensitive persons, whereby the latter displayed increased neural entropy. The findings support the central theoretical assumption of enhanced information processing and could be important for developing biomarkers for clinical diagnostics.

[Proposal of a Basic Documentation for Child, Adolescent and Family Psychosomatics Based on a Synopsis of Basic Documentations for Children, Adolescents and Adults]. / Vorschlag einer Basisdokumentation für die Kinder-, Jugend- und Familienpsychosomatik auf Basis einer Synopsis von Basisdokumentationen für Kinder, Jugendliche und Erwachsene.

BACKGROUND: In psychiatry, psychosomatics and psychotherapy, basic documentation (BaDo) is used as a quality assurance tool. For the field of child, adolescent and family psychosomatics, there is no uniform BaDo that can be used across facilities and care areas. The aim of the study was to propose a catalog of characteristics for the context of psychosomatic treatment of children and adolescents on the basis of a synoptic comparison of established BaDos METHODS: In the context of a qualitative document analysis, BaDo items from the children/youth and adult sector were evaluated in content analysis along a category system. The resulting aspects were then classified according to age and multidisciplinary content and evaluated with regard to their child/youth specificity. Descriptive statistical analysis of the results was performed RESULTS: Aspects of the categories Family Anamnesis and Biographical Anamnesis specified a BaDo for children and adolescents. For BaDos from the psychosomatic field, a record of pre-treatments was accentuated across age groups. The recording of socio-demographic data had to be adapted conceptually to the age-related needs of children and adolescents. CONCLUSION: On the basis of an empirical approach, a modular BaDo for child, youth and family psychosomatics could be formulated that enables institutional, sectoral and interdisciplinary evaluations. In a next step, the instrument should be evaluated in an application study and be consented to on a broad level.

L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry.

BACKGROUND: Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by anemia, short stature, congenital anomalies, and cancer predisposition. Most cases are due to mutations in genes encoding ribosomal proteins (RP) leading to RP haploinsufficiency. Effective treatments for the anemia of DBA include chronic red cell transfusions, long-term corticosteroid therapy, or hematopoietic stem cell transplantation. In a small patient series and in animal models, there have been hematologic responses to L-leucine with amelioration of anemia. The study objectives of this clinical trial were to determine feasibility, safety, and efficacy of L-leucine in transfusion-dependent patients with DBA. PROCEDURE: Patients ≥2 years of age received L-leucine 700 mg/m2 orally three times daily for nine months to determine a hematologic response and any improvement in growth (NCT01362595). RESULTS: This multicenter, phase I/II study enrolled 55 subjects; 43 were evaluable. There were 21 males; the median age at enrollment was 10.4 years (range, 2.5-46.1 years). No significant adverse events were attributable to L-leucine. Two subjects had a complete erythroid response and five had a partial response. Nine of 25, and 11 of 25, subjects experienced a positive weight and height percentile change, respectively, at the end of therapy. CONCLUSIONS: L-leucine is safe, resulted in an erythroid response in 16% of subjects with DBA, and led to an increase in weight and linear growth velocity in 36% and 44% of evaluable subjects, respectively. Further studies will be critical to understand the role of L-leucine in the management of patients with DBA.

Why are some cases not on track? An item analysis of the Assessment for Signal Cases during inpatient psychotherapy.

Within the Routine Outcome Monitoring system "OQ-Analyst," the questionnaire "Assessment for Signal Cases" (ASC) supports therapists in detecting potential reasons for not-on-track trajectories. Factor analysis and a machine learning algorithm (LASSO with 10-fold cross-validation) were applied, and potential predictors of not-on-track classifications were tested using logistic multilevel modeling methods. The factor analysis revealed a shortened (30 items) version of the ASC with good internal consistency (α = 0.72-0.89) and excellent predictive value (area under the curve = 0.98; positive predictive value = 0.95; negative predictive value = 0.94). Item-level analyses showed that interpersonal problems captured by specific ASC items (not feeling able to speak about problems with family members; feeling rejected or betrayed) are the most important predictors of not-on-track trajectories. It should be considered that our results are based on analyses of ASC items only. Our findings need to be replicated in future studies including other potential predictors of not-on-track trajectories (e.g., changes in medication, specific therapeutic techniques, or treatment adherence), which were not measured this study.

[The "popular saint" Therese of Konnersreuth and her stigmata : An historical example for the interaction of psyche and religiosity]. / Die "Volksheilige" Therese Neumann von Konnersreuth und ihre Stigmata : Ein historisches Beispiel zur Wechselwirkung von Psyche und Religiosität.

BACKGROUND: In present times, we see ourselves confronted by the challenge of engaging increasingly diverse views of the world, god and healing in a constructive dialogue. Consequently, it is important to research into the contrary effects of religiosity on the human psyche. METHODS: Original- and literary medical historian research RESULTS: Gottfried Ewald (1888-1963), a psychiatric expert at the Friedrich-Alexander University of Erlangen, was appointed 90 years ago with the task of examining Therese Neumann (1898-1962), colloquially known as Resl of Konnersreuth. In 1927, Ewald retrospectively confirmed the diagnosis of "most severe hysteria with blindness and partial paralysis". Within the context of regular pastoral care, Resl's "hysterical blindness" disappeared on 24.06.1923. This remission might be ascribed to a positive effect of religiosity on mental health. Besides the beneficial effects of religiosity on healing, pathogenic phenomena of religion can also be seen in the case of Resl. During Lent in 1926, Resl experienced ecstatic states as well as blood-stained tears. On Good Friday in 1926, bleeding of the scalp occurred; since Holy Saturday 1927, she experienced stigmata on her hands and the soles of her feet. Ewald assessed the latter as probably being genuine, although he spoke in favor of a clinical observation in hospital to obtain scientifically substantiated findings. DISCUSSION: The story of Resl of Konnersreuth shows the contrary influences of religiosity on mental health in one and the same individual. CONCLUSION: Detailed psychiatric historical and ethical research on the interaction of the psyche and religiosity can provide information about mechanisms that channel the psychic power of religiosity to promote remission. It is further important to take a religious and spiritual history of the patients.

[500 Years of Reformation: The History of Martin Luther's Pathography and its Ethical Implications]. / 500 Jahre Reformation: Zur Historie der Pathographie Martin Luthers und ethischen Implikationen.

Introduction In the context of the 500th anniversary of the Reformation, it is time to take a survey of the history of Martin Luther's (1483-1546) pathography and to deduce possible conclusions from it for psychiatric practice. Results In a 1035-page work written in German between 1937 and 1941, the Dane Paul Reiter retrospectively diagnosed Luther as manic-depressive. In 1956, Grossmann was unable to prove persistent synchronicity of depressive mood and reduced motivation in Luther in the key years 1527 and 1528, which led him to conclude that Luther had a cyclothymic personality with a pyknic constitution. Discussion One very central source of Luther's life's work may have arisen from the tension between emotional constraints and crises of faith, on the one hand, and resilience and trust in God, on the other. Conclusion Luther can be used as an example of the importance of religiousness as a curative resource for the psyche.

Relation Between Obesity, Metabolic Syndrome, Successful Long-Term Weight Reduction, and Right Ventricular Function.

This study sought to examine the relationships between right ventricular (RV) function and geometry, morbid obesity with and without the metabolic syndrome, and the effect of long-term weight loss. Obese (n = 153, BMI 41.2 ± 8.7 kg/m(2)) and healthy non-obese control subjects (n = 38, BMI 25.5 ± 3.3 kg/m(2)) of similar age and gender distribution were prospectively studied during the course of a 1-year weight reduction program with echocardiography at baseline and after one year of follow up. Function and geometry of the right heart were evaluated by tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TDI S'), RV myocardial performance index (TEI), RV end-diastolic (RVEDD) and end-systolic diameter (RVESD), area of the right atrium (RAA), and systolic pulmonary artery pressure (PAP). Whereas parameters of systolic and diastolic LV function were significantly worse in the obese subjects than those in the non-obese subjects (EF 66 ± 6 versus 69 ± 6%, P = 0.004; E/E' 7.4 ± 2.5 versus 6.3 ± 2.6, P = 0.010), parameters of RV function (TAPSE 25.6 ± 4.5 versus 25.1 ± 3.5 mm, P = 0.528; TDI S' 13.5 ± 2.9 versus 13.8 ± 2.9 mm/second, P = 0.553; TEI 0.25 ± 0.13 versus 0.28 ± 0.09, P = 0.283) as well as geometry measurements were comparable between the obese and non-obese participants and also in obese subjects with full blown metabolic syndrome. Additionally, successful weight reduction did not alter the RV parameters. Nevertheless, in the few obese subjects with RV dysfunction (n = 7), metabolic syndrome parameters were more pronounced than in obese with normal RV function.Morbid obesity with and without the metabolic syndrome is accompanied by an impaired LV systolic and diastolic function. In contrast, RV function appears to be less affected by obesity independent of the presence of the metabolic syndrome.

Successful weight reduction improves left ventricular diastolic function and physical performance in severe obesity.

Obesity and the metabolic syndrome (MetS) are risk factors for left ventricular diastolic dysfunction (LVDD). However, little is known about the impact of successful weight reduction (WR) on diastolic function and physical performance.Obese subjects (øBMI 40.2 ± 8.6 kg/m(2)) underwent a 1-year WR program comprising diet and lifestyle components. Echocardiography and exercise capacity (6-minute walk) were performed at baseline and after 1 year. The distribution of weight reduction was split at the sample median and subjects were dichotomized in "successful WR" (% WR ≥ median, corresponding to a weight loss of 8%) and "failed-WR" (% WR < median).From a total of 188 obese subjects, 71 had LVDD at baseline. Obese patients with successful WR improved their MetS alterations, including fasting glucose, insulin, lipids, adipokines, blood pressure levels, and epicardial fat thickness. The same was not true for obesity with failed WR. Subjects with successful WR demonstrated significant improvement in echocardiographic LVDD parameters (median [interquartile range]): Δe' (2,5 [-1.0, 4.7], P < 0.01), Δe'/a' (0.34 [0.07, 079], P < 0.01), ΔE/e' (-1.14 [-2.72, -0.54], P < 0.05), ΔE/A (0.08 [-0.04, 0.26], P < 0.05), ΔArd-Ad (-28 [-54, -4], P < 0.01), and 6-minute walk distance (65 [19, 135], P < 0.01). Improvement of ≥ 2 LVDD criteria was accomplished in 30% of subjects with WR versus 10% without (P = 0.009). Using multivariable regression analysis, reduction of epicardial fat thickness was particularly predictive for the improvement of diastolic function.In summary, in severe obesity, successful long-term WR was associated with improved LV diastolic function and exercise capacity.

[The ICD-10 Symptom Rating (ISR): validation of the depression scale in a clinical sample]. / Das ICD-10 Symptomrating (ISR): Validierung der Depressionsskala an einer klinischen Stichprobe.

The ICD-10 Symptom Rating (ISR) 1 measures the severity of psychiatric disorders with 29 items on 5 subscales as comprehensively as possible. The following syndromes are measured: Depressive syndrome, anxiety syndrome, obsessive-compulsive syndrome, Somatoform syndrome, eating disorder syndrome as well as additional items that cover various mental syndromes, and an overall score. The study reports findings on the validity and sensitivity to change of the depression subscale (ISR-D). In a clinical sample of N=949 inpatients with depression spectrum disorders the convergent validity was determined by correlation with the Beck Depression Inventory (BDI) 3 and the subscale "depression" of the Symptom-Checklist-90-R (SCL-90-R) 4. The high correlation between the different instruments confirms the validity of the ISR-Depression Scale. The sensitivity to change of the ISR seems higher than that of the BDI and the SCL-90. Because of its economy and the good psychometric properties the ISR is recommended for use in clinical samples.

Extreme deviations from expected recovery curves and their associations with therapeutic alliance, social support, motivation, and life events in psychosomatic in-patient therapy.

OBJECTIVES: Within the clinical support tools (CST) of the OQ-Analyst, the "Assessment for Signal Cases" (ASC) evaluates the therapeutic alliance, social support, motivation, and life events. We investigated whether the ASC covers domains of importance in treatment weeks with extreme deviations from expected recovery curves (ERCs). METHODS: Psychosomatic in-patients were monitored weekly with the ASC and the "Outcome Questionnaire" (OQ-45). The ERCs of the OQ-45 empirical algorithm were used to define treatment weeks with extreme positive deviations (EPD), extreme negative deviations (END), or without extreme deviations (NO). Associations between the ASC scales and EPD as well as END were analyzed by multilevel models. RESULTS: While each ASC scale was positively associated with EPD, only the social support and life events scales were negatively related to END. CONCLUSIONS: CSTs prioritizing social support and life events might be more effective in preventing treatment failure.

Effectiveness of a multimodal treatment program for somatoform pain disorder.

Chronic pain conditions are highly prevalent, with somatoform pain disorder accounting for a large proportion. However, the psychological forms of treatment currently used achieve only small to medium effect sizes. This retrospective study investigated the effectiveness of a 5-week multimodal pain program for patients with somatoform pain disorder. The diagnosis of somatoform pain disorder was confirmed by a specialist for anesthesiology and pain management and a specialist for psychosomatic medicine. Therapy outcome was evaluated with a Numeric Rating Scale (NRS), the Pain Disability Index (PDI), and the Pain Perception Scale. Within the study sample (n = 100), all parameters showed a significant and clinically relevant improvement at the end of therapy (P values < 0.001). The highest effect sizes (d) were found for reduction in average pain rating (NRS: d = 1.00) and the affective items of the Pain Perception Scale (SES-A: d = 0.07). The lowest effect sizes were found for improvement of pain-related disabilities (PDI: d = 0.42) and sensory items of the Pain Perception Scale (SES-S: d = 0.50). Despite high chronification of pain condition, with average pain duration of greater than 8 years, the multimodal treatment program showed medium to large effect sizes on the outcome of patients with somatoform pain disorder. Compared with previous data with small to moderate effect sizes, a multimodal program seems to be more effective than other interventions to address somatoform pain disorder.

Healing beyond the joint: Addressing mental health in periprosthetic joint infection in a prospective longitudinal study.

OBJECTIVE: Periprosthetic joint infection (PJI) is a devastating complication following joint replacement surgeries. While the somatic impacts of PJI have been extensively explored, the influence on mental health remains understudied. This study aimed to longitudinally assess the psychological burden, quality of life, and expectations in individuals undergoing treatment for PJI. METHODS: A prospective study was conducted at a German trauma center between January 2020 and December 2022. Patients diagnosed with PJI (n = 29, mean age 71.4 ± 8.8 years) were assessed at five timepoints, within one week before revision surgery, one month, three, six, and twelve months postoperatively. Outcomes included the ICD-10 symptom-rating (ISR), German Short-Form 36 (SF-36), European Quality of Life 5 Dimensions (EQ-5D), and an expectation questionnaire. RESULTS: Psychological scores exhibited significant upward trends over time. The ISR score increased from 0.55 preoperatively to 0.87 at the 12-month follow-up (p = 0.002), surpassing the clinically relevant threshold. Depression and anxiety scores peaked at 6 months (1.6, p = 0.005) and 12 months (1.12, p = 0.001), respectively. Quality of life, measured by SF-36, showed stable physical component summary scores but declining mental component summary scores. Patients' expectations of returning to normal health consistently decreased (p = 0.009). CONCLUSION: Patients undergoing treatment for PJI experience significant psychological burden, with implications for quality of life and expectations of recovery. The findings underscore the importance of addressing psychological well-being in the management of PJI and emphasize the need for comprehensive care strategies that encompass both somatic and psychological dimensions.

Waning waves of mood: The declining trend of hospitalized patients with affective disorders in Germany.

INTRODUCTION: Affective disorders profoundly affect individuals' emotional well-being and quality of life. This study investigates the epidemiology of affective disorders in Germany from 2011 to 2021, focusing on incidence rates, age- and sex-standardized rates, and developmental trends. METHODS: Using nationwide data of ICD-10 diagnosis codes from 2011 to 2021, this cross-sectional study analyzed inpatient cases of affective disorders in individuals aged 20 years or older. Age- and sex-standardized incidence rates were calculated based on the population size of each birth cohort in the 16 German federal states. Incidence rate ratios (IRRs) for 2011 to 2021 and 2019 to 2021 were compared with a two-sample z-test. RESULTS: Between 2011 and 2021, F30 (manic episode) showed a decline of 42.8 % to an incidence of 4.9 per 100,000 inhabitants, even though not statistically significant (p = 0.322). F31 (bipolar affective disorder) remained relatively stable with a reduction of 15.3 % to an incidence of 13.6 per 100,000 inhabitants in 2021 (p = 0.653). F32 (depressive episode) decreased statistically significant by 25.7 % to an incidence of 64.1 per 100,000 inhabitants (p = 0.072). F33 (recurrent depressive disorder) slightly increased by 18.3 % to an incidence of 94.6 per 100,000 inhabitants (p = 0.267). No statistically significant differences were found when comparing the COVID-19 pandemic year 2021 to 2019 incidences (p ≥ 0.529). CONCLUSION: The study provides valuable insights into the changing landscape of affective disorders in Germany over the past decade. The observed decline in incidence rates underscores the importance of continued efforts to promote mental health awareness and access to care.

Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971.

Transient myeloproliferative disorder (TMD), restricted to newborns with trisomy 21, is a megakaryocytic leukemia that although lethal in some is distinguished by its spontaneous resolution. Later development of acute myeloid leukemia (AML) occurs in some. Prospective enrollment (n = 135) elucidated the natural history in Down syndrome (DS) patients diagnosed with TMD via the use of uniform monitoring and intervention guidelines. Prevalent at diagnosis were leukocytosis, peripheral blast exceeding marrow blast percentage, and hepatomegaly. Among those with life-threatening symptoms, most (n = 29/38; 76%) received intervention therapy until symptoms abated and then were monitored similarly. Organomegaly with cardiopulmonary compromise most frequently led to intervention (43%). Death occurred in 21% but only 10% were attributable to TMD (intervention vs observation patients: 13/14 vs 1/15 because of TMD). Among those solely observed, peripheral blasts and all other TMD symptoms cleared at a median of 36 and 49 days from diagnosis, respectively. On the basis of the diagnostic clinical findings of hepatomegaly with or without life-threatening symptoms, 3 groups were identified with differing survival: low risk with neither finding (38%), intermediate risk with hepatomegaly alone (40%), and high risk with both (21%; overall survival: 92% ± 8%, 77% ± 12%, and 51% ± 19%, respectively; P ≤ .001). Among all, AML subsequently occurred in 16% at a median of 441 days (range, 118-1085 days). The trial is registered at http://www.clinicaltrials.gov as NCT00003593.

Attention deficits and depressive symptoms improve differentially after rehabilitation of post-COVID condition - A prospective cohort study.

BACKGROUND: Depressive and cognitive symptoms like fatigue, loss of energy or sleep disorders characterise the post-COVID condition. Post-COVID psychosomatic rehabilitation should focus on both symptom groups. The current prospective cohort study addresses the change in these symptoms in the context of a psychosomatic rehabilitation. METHOD: N = 80 patients with post-COVID symptoms underwent psychological testing on admission and discharge: PHQ-9 questionnaire for depression, TAP - test battery for the attention test with the sub-tests working memory, sustained attention, divided attention and alertness. Sample characteristics, including health-related and work-related parameters, the general symptom load and the course of symptoms during the five weeks of rehabilitation were evaluated. RESULTS: On admission, the PHQ-9 indicated the presence of depressive symptoms in post-COVID patients (PHQ-9 = 15.15 ± 5.11). Over the course of rehabilitation, the depressive symptoms decreased to a sub-clinical level (PHQ-9 = 8.80 ± 4.61), suggesting a strong effect of post-COVID inpatient rehabilitation (Cohen's d = 1.57). At the same time, post-COVID patients showed clinically relevant impairments in attention and working memory that persisted throughout the rehabilitation period despite multimodal post-COVID treatment. CONCLUSION: Over the course of post-COVID rehabilitation, depressive symptoms appear to be significantly reduced. With regard to cognitive impairment, a comparable effect within the short period of 5 weeks is not evident. Our results suggest the need for specific treatment of persistent neuropsychological deficits following post-COVID rehabilitation.

Neurophysiological signatures of sensory-processing sensitivity.

Background: Sensory processing sensitivity is mainly captured based on questionnaires and it's neurophysiological basis is largely unknown. As hitherto no electroencephalography (EEG) study has been carried out, the aim of this work was to determine whether the self-reported level of SPS correlates with the EEG activity in different frequency bands. Methods: One hundred fifteen participants were measured with 64-channel EEG during a task-free resting state. After artifact correction, a power spectrum time series was calculated using the Fast Fourier Transform (FFT) for the following frequency bands: Delta: 1-3.5 Hz, theta: 4-7.5 Hz, alpha1: 8-10 Hz, alpha2: 10.5-12 Hz, beta1: 12.5-15 Hz, beta2: 15.5-25 Hz, gamma: 25.5-45 Hz, global: 1-45 Hz. Correlations with the 'Highly Sensitive Person Scale' (HSPS-G) scores were determined. Then, the lowest and the highest 30% of the cohort were contrasted as polar opposites. EEG features were compared between the two groups applying a paired two-tailed t-test. Results: The HSPS-G scores correlated statistically significantly positive with beta 1 and 2, and global EEG power during resting with eyes open, but not during resting with eyes closed. The highly sensitive group revealed higher beta power (4.38 ± 0.32 vs. 4.21 ± 0.17, p = 0.014), higher gamma power (4.21 ± 0.37 vs. 4.00 ± 0.25, p = 0.010), and increased global EEG power (4.38 ± 0.29 vs. 4.25 ± 0.17, p = 0.041). The higher EEG activity in the HSP group was most pronounced in the central, parietal, and temporal region, whereas lower EEG activity was most present in occipital areas. Conclusion: For the first time, neurophysiological signatures associated with SPS during a task free resting state were demonstrated. Evidence is provided that neural processes differ between HSP and non-HSP. During resting with eyes open HSP exhibit higher EEG activity suggesting increased information processing. The findings could be of importance for the development of biomarkers for clinical diagnostics and intervention efficacy evaluation.

A multilocus genetic risk score for obesity: Association with BMI and metabolic alterations in a cohort with severe obesity.

Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with obesity, yet effect sizes of individual SNPs are small. Therefore, the aim of our study was to investigate whether a genetic risk score (GRS) comprising risk alleles of SNPs identified in the GIANT consortium meta-analyses shows association with body mass index (BMI) and other BMI related metabolic alterations in a cohort with an extreme phenotype. Genotyping of 93 SNPs was performed in 314 obese individuals (mean BMI 40.5 ± 7.8 kg/m², aged 45 ± 12 years), participating in a standardized weight reduction program, and in 74 lean controls (mean BMI 24.6 ± 3.3 kg/m², aged 41.7 ± 13.4 years). Allele numbers of all 93 SNPs were added to a GRS. Anthropometric parameters, parameters of glucose/insulin and lipid metabolism were assessed standardized after a 12 hours fast. GRS was significantly different between controls and obese individuals (unweighted GRS: 86.6 vs 89.0, P = .002; weighted GRS: 84.9 vs 88.3, P = .005). Furthermore, linear regression analysis showed significant associations of GRS with BMI ( P < .0001), weight ( P = .0005), waist circumference ( P = .0039), fat mass ( P < .0001) and epicardial fat thickness ( P = .0032), yet with small effect sizes ( r ² < 0.06). In conclusion, in our study GRS could differentiate between extreme obese and lean individuals, and was associated with BMI and its related traits, yet with small effect sizes.

Improvement of obstructive sleep apnea does not rescue left atrial enlargement in obese participants of a multimodal weight reduction program.

The aim of our study was to investigate the effect of obstructive sleep apnea (OSA) and its weight loss related improvement on left atrial (LA) area in individuals with severe obesity participating in a multimodal weight reduction (WR) program. Participants with obesity (body mass index, BMI, 40.2 ± 7.3 kg/m2) underwent a 1-year WR program. Phenotyping was performed at baseline and after 12 months. Individuals were categorized according to their baseline apnea-hypopnea-index (AHI) into "no OSA" (AHI < 5) and "OSA" (AHI ≥ 5). From a total of 84 study participants, 69 completed the program. Average WR was 19.0 ± 15.7 kg after 12 months. Participants with obesity and OSA had a larger LA area at baseline as compared to participants with obesity but without OSA (22.4 ± 5.6 vs 18.8 ± 3.8 cm2; P = .008). Linear regression showed significant associations of AHI and BMI with LA area. In contrast, despite a significant decrease of AHI in participants with OSA as compared to those without OSA at 1 year follow up (ΔAHI was -12 ± 14) ΔLA area did not significantly differ between groups. Multivariable linear regression showed no significant association of ΔAHI or ΔBMI with ΔLA. In conclusion, the presence of obstructive sleep apnea contributes to LA enlargement on top of obesity in our study cohort. Yet, successful WR with subsequently improved OSA was not associated with an improvement of LA area.

Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group trial A2971: a report from the Children's Oncology Group.

BACKGROUND: Children who are treated for myeloid leukemia associated with Down syndrome (DS) experience superior survival compared with children who have myeloid leukemia without DS. To maintain excellent outcomes while avoiding toxicity, the Children's Oncology Group (COG) conducted the phase 3 trial COG A2971, the first trial solely designed to provide uniform treatment of myeloid leukemia in North American children with DS. A2971 eliminated 2 induction drugs and 3 months of maintenance therapy from the standard-timing regimen of dexamethasone, cytarabine, 6-thioguanine, etoposide, and rubidomycin/daunomycin (DCTER) used in the previous study (Children's Cancer Group [CCG] 2891). METHODS: COG A2971 was a multi-institutional, nonrandomized, clinical trial that enrolled 132 patients who had DS with either acute myeloid leukemia (n = 91) or myelodysplastic syndrome (n = 41). RESULTS: The median follow-up was 4.8 years (range, 0.8-8.6 years), the median age at diagnosis was 1.7 years (range, 0.3-13.6 years), and the median white blood cell count was 6200/µL (range, 900-164,900/µL). The remission rate (92.7% ± 6%) was similar to that reported in the CCG 2891 study (91.3% ± 5%; P = .679). The 5-year event free survival (EFS) rate was 79% ± 7% (vs 77% ± 7% in CCG 2891; P = .589), the disease-free survival (DFS) rate was 89% ± 6% (vs 85% ± 6% in CCG 2891; P = .337), and the overall survival rate was 84% ± 6% (vs 79% ± 7% in CCG 2891; P = .302). Induction day-14 bone marrow response trended toward a more favorable outcome (EFS: P = .12). Age >4 years was an adverse risk factor (5-year EFS rate: 33% ± 38% for children aged >4 years [median, 8.5 years; n = 6] vs 81% ± 7% for children ages 0-4 years [median, 1.7 years; n = 126]; P = .001). CONCLUSIONS: The COG A2971 trial reduced the chemotherapy dose and maintained survival to that achieved by the CCG 2891 trial in children who had myeloid leukemia associated with DS.