The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta-analysis.

OBJECTIVES: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra-cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification. METHODS: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010-February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF-PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747. RESULTS: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%-21.6%), 9.3% (95% CI, 6.6%-12.3%) and 35.9% (95% CI, 21.0%-52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%-65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%). CONCLUSION: The likelihood of a monogenic aetiology in fetuses with multi-system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.

New insights into the electronic structure ofα-U andδ-Pu.

This work presents the results of a theoretical study of the electronic structure of two actinide metals,α-U andδ-Pu. We compare ourab-initioresults obtained with the recently developed self-consistent Vertex corrected GW approach with previously published experimental measurements such as photo-electron spectroscopy, for the occupied density of states, and bremsstralung isochromat spectroscopy (BIS) and inverse photo-electron spectroscopy (IPES), for the unoccupied density of states. Ourab-initioapproach includes all important relativistic effects (it is based on Dirac's equation) and it represents the first application of the Vertex corrected GW approach in the physics of actinides. Overall, our theoretical results are in good agreement with the experimental data, which supports the level of approximations which our theoretical method is based upon. By comparing our vertex corrected GW results with our results obtained with less sophisticated approaches (local density approximation and self-consistent GW) we differentiate the strength of correlation effects in Uranium and Plutonium. Also, our theoretical results allow us to elucidate the subtle differences between the previously published experimental BIS and IPES data on the unoccupied density of states inα-U.

Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The first interim analysis of the phase III, randomized, double-blind, placebo-controlled, multinational TITAN study demonstrated improved overall survival (OS) and radiographic progression-free survival (rPFS) with apalutamide added to ongoing androgen deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer. The final analysis confirmed improvement in OS and other long-term outcomes. We evaluated prostate-specific antigen (PSA) kinetics and the association between PSA decline and outcomes in patients with metastatic castration-sensitive prostate cancer from TITAN. PATIENTS AND METHODS: Patients received apalutamide (240 mg/day) or placebo plus ADT (1 : 1). This post hoc exploratory analysis evaluated PSA kinetics and decline in relation to rPFS (22.7 months' follow-up) and OS, time to PSA progression, and time to castration resistance (44.0 months' follow-up) in patients with or without confirmed PSA decline using a landmark analysis, the Kaplan-Meier method, and Cox proportional hazards model. RESULTS: One thousand and fifty-two patients (apalutamide, 525; placebo, 527) were enrolled. Best confirmed PSA declines (≥50% or ≥90% from baseline or to ≤0.2 ng/ml) were achieved at any time during the study in 90%, 73%, and 68% of apalutamide-treated versus 55%, 29%, and 32% of placebo-treated patients, respectively. By 3 months of apalutamide treatment, best deep PSA decline of ≥90% or to ≤0.2 ng/ml occurred in 59% and 51% of apalutamide- and in 13% and 18% of placebo-treated patients, respectively. Achievement of deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer OS [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.25-0.48), rPFS (HR 0.44; 95% CI 0.30-0.65), time to PSA progression (HR 0.31; 95% CI 0.22-0.44), and time to castration resistance (HR 0.38; 95% CI 0.27-0.52) compared with no decline (P < 0.0001 for all). Similar results were observed at landmark 6 and 12 months of apalutamide treatment. CONCLUSIONS: Apalutamide plus ADT demonstrated a robust (rapid, deep, and durable) PSA decline that was associated with improved clinical outcomes, including long-term survival.

Erythema annulare centrifugum induced by COVID-19 vaccination.

With the expansion of the COVID-19 vaccination drive, an increasing number of adverse effects are surfacing. A 74-year-old woman presented with multiple erythematous and itchy patches on several sites. She had no relevant medical history, apart from the first AZD1222 vaccination 1 month previously. Microscopically, epidermal changes, including mild spongiosis and parakeratosis, were observed. Tight perivascular lymphocytic infiltration (coat-sleeve pattern) was also observed in the dermis. The final diagnosis was erythema annulare centrifugum (EAC) induced by SARS-CoV-2 vaccination. Based on this report, dermatologists should be aware of the possibility of EAC from the AZD1222 vaccination.

Regional Aneurysm Wall Enhancement is Affected by Local Hemodynamics: A 7T MRI Study.

BACKGROUND AND PURPOSE: Aneurysm wall enhancement has been proposed as a biomarker for inflammation and instability. However, the mechanisms of aneurysm wall enhancement remain unclear. We used 7T MR imaging to determine the effect of flow in different regions of the wall. MATERIALS AND METHODS: Twenty-three intracranial aneurysms imaged with 7T MR imaging and 3D angiography were studied with computational fluid dynamics. Local flow conditions were compared between aneurysm wall enhancement and nonenhanced regions. Aneurysm wall enhancement regions were subdivided according to their location on the aneurysm and relative to the inflow and were further compared. RESULTS: On average, wall shear stress was lower in enhanced than in nonenhanced regions (P = .05). Aneurysm wall enhancement regions at the neck had higher wall shear stress gradients (P = .05) with lower oscillations (P = .05) than nonenhanced regions. In contrast, aneurysm wall enhancement regions at the aneurysm body had lower wall shear stress (P = .01) and wall shear stress gradients (P = .008) than nonenhanced regions. Aneurysm wall enhancement regions far from the inflow had lower wall shear stress (P = .006) than nonenhanced regions, while aneurysm wall enhancement regions close to the inflow tended to have higher wall shear stress than the nonenhanced regions, but this association was not significant. CONCLUSIONS: Aneurysm wall enhancement regions tend to have lower wall shear stress than nonenhanced regions of the same aneurysm. Moreover, the association between flow conditions and aneurysm wall enhancement seems to depend on the location of the region on the aneurysm sac. Regions at the neck and close to the inflow tend to be exposed to higher wall shear stress and wall shear stress gradients. Regions at the body, dome, or far from the inflow tend to be exposed to uniformly low wall shear stress and have more aneurysm wall enhancement.

Overcoming existential loneliness: a cross-cultural study.

BACKGROUND: Moving into a long-term care facility (LTCF) can reduce the ability for older adults to engage in meaningful roles and activities and the size of their social network. These changes and losses can lead them to experience existential loneliness (EL)-the intolerable emptiness and lack of meaningful existence resulted from the losses they have experienced. While EL has often been understood as a universal human experience, it has primarily been studied in people from Western cultures; little is known about how EL may be experienced by and manifested in people from Eastern cultures. Hence, this qualitative study aimed to describe the experience and coping of EL in Hong Kong Chinese and Swedish older adults living in LTCFs. METHODS: A qualitative study using Thorne's (2004) interpretive description was conducted. Thirteen Chinese and 9 Swedes living in LTCFs in Hong Kong, China and Malmo, Sweden, respectively were interviewed about their experience of EL in two series of semi-structured interviews. Data were analyzed using thematic analysis. RESULTS: The core theme of "overcoming EL" described the participants' experience of EL, which came about through the combined process of "Feeling EL" and "Self-Regulating". Both Chinese and Swedish participants had similar experience with EL. Realizing that they did not want to living with EL anymore, they coped by reframing their experience and identifying new meaning in their life. CONCLUSIONS: The study findings suggested that early and clear counselling support that help older adults to define new meaning in life may help them cope. In addition, more opportunities should be available at the LTCFs to promote quality relationships, enable older adults to reflect on their lives with pride, and support their ability to do the things they enjoy.

[Pilot study on subjectively and objectively measurable stress reduction in the daily routine of a university anesthesia department by an intervention program according to mindfulness-based stress reduction]. / Pilotstudie zu subjektiv und objektiv messbarer Stressreduktion im Alltag einer universitären Anästhesieabteilung durch ein Interventionsprogramm nach Mindfulness-Based Stress Reduction (MBSR).

BACKGROUND: Chronic stress and high workload in physicians can lead to loss of interest, emotional exhaustion and finally in burnout syndrome. This can cause serious consequences not only for the physicians personally and their own health by developing extensive health impairments, e.g. depression, suicide, substance abuse and poor self-care but also for patient care, reflected in an increase of medical errors, longer recovery times, lower care quality and consequently lower patient satisfaction. Additionally, it can also have negative effects on the healthcare system by reduced productivity, increased physician turnover and thereby higher costs. OBJECTIVE: This pilot study investigated brief interventions inspired by mindfulness-based stress reduction (MBSR) combined with short daily meditation exercises in the everyday work of anesthetists at a university hospital. Secondly, whether this program increases the development of coping mechanisms for stress and improves participants' resilience and health status. MATERIAL AND METHODS: The pilot study was designed as a monocenter prospective interventional study with four different points of measurement. Subjective and objective stress parameters were measured directly before (t0) and after (t1) the intervention as well as 3 (t2) and 6 (t3) months after end of the intervention. Measurements took place during work time and at the workplace. The intervention was based on the classical MBSR including short daily exercises and lasted for 6 weeks with sessions lasting 1- 1.5 h and an additional 20 min of daily mediation exercises. The subjective parameters were based on validated questionnaires, such as the World Health Organization (WHO) well-being index (WHO-5), resilience scale (RS-11), Maslach burnout inventory (MBI-22) and perceived stress scale (PSS-10). For objective parameters heart rate variability (HRV) was evaluated during rest and after exposure to physical exercise and hair cortisol concentrations (HCC) in a 1.5 cm length of a hair, which represents the equivalent of a 6-week period. RESULTS: Data from 27 subjects could be analyzed. Between t3 and t0 a significant improvement of resilience was detected as a positive personality trait measured by RS-11 with a large effect size (p = 0.013; r = 0.59) as well as a significant reduction of burnout symptoms (MBI-22) also with a large effect size (p = 0.019; r = 0.57). Furthermore, a significant decrease was found in well-being (WHO-5) between t2 and t0 (p = 0.003, r = 0.67) and between t1 and t0 (p = 0.001, r = 0.71). The objective parameters did not show any significant differences between the examinations. CONCLUSION: An MBSR-based intervention in combination with short exercises during and after work can be implemented in daily work of anesthetists at a university hospital. Furthermore, there was clear evidence that the intervention program increased resilience and reduced burnout symptoms for up to 6 months. These findings are in line with the literature that MBSR reduces risk of burnout symptoms. The decrease in well-being might be biased by a high amount of socially accepted answers at the beginning of the study (t0).

Artificial Intelligence for the Future Radiology Diagnostic Service.

Radiology historically has been a leader of digital transformation in healthcare. The introduction of digital imaging systems, picture archiving and communication systems (PACS), and teleradiology transformed radiology services over the past 30 years. Radiology is again at the crossroad for the next generation of transformation, possibly evolving as a one-stop integrated diagnostic service. Artificial intelligence and machine learning promise to offer radiology new powerful new digital tools to facilitate the next transformation. The radiology community has been developing computer-aided diagnosis (CAD) tools based on machine learning (ML) over the past 20 years. Among various AI techniques, deep-learning convolutional neural networks (CNN) and its variants have been widely used in medical image pattern recognition. Since the 1990s, many CAD tools and products have been developed. However, clinical adoption has been slow due to a lack of substantial clinical advantages, difficulties integrating into existing workflow, and uncertain business models. This paper proposes three pathways for AI's role in radiology beyond current CNN based capabilities 1) improve the performance of CAD, 2) improve the productivity of radiology service by AI-assisted workflow, and 3) develop radiomics that integrate the data from radiology, pathology, and genomics to facilitate the emergence of a new integrated diagnostic service.