The Best of Both Worlds: Ultra-high-pitch Pulmonary Angiography with Free-Breathing Technique by Means of Photon-Counting Detector CT for Diagnosis of Acute Pulmonary Embolism.

RATIONALE AND OBJECTIVES: To assess image quality and radiation dose of ultra-high-pitch CT pulmonary angiography (CTPA) with free-breathing technique for diagnosis of pulmonary embolism using a photon-counting detector (PCD) CT compared to matched energy-integrating detector (EID)-based single-energy CTPA. MATERIALS AND METHODS: Fifty-one PCD-CTPAs were prospectively compared to 51 CTPAs on a third-generation dual-source EID-CT. CTPAs were acquired with an ultra-high-pitch protocol with free-breathing technique (40 mL contrast medium, pitch 3.2) at 140 kV (PCD) and 70-100 kV (EID). Iodine maps were reconstructed from spectral PCD-CTPAs. Image quality of CTPAs and iodine maps was assessed independently by three radiologists. Additionally, CT attenuation numbers within pulmonary arteries as well as signal-to-noise and contrast-to-noise ratios (SNR, CNR) were compared. Administered radiation dose was compared. RESULTS: CT attenuation was higher in the PCD-group (all P < 0.05). CNR and SNR were higher in lobar pulmonary arteries in PCD-CTPAs (P < 0.05), whereas no difference was ascertained within the pulmonary trunk (P > 0.05). Image quality of PCD-CTPA was rated best by all readers (excellent/good image quality in 96.1% of PCD-CTPAs vs. 50.9% of EID-CTPAs). PCD-CT produced no non-diagnostic scans vs. three non-diagnostic (5.9%) EID-CTPAs. Radiation dose was lower with PCD-CT than with EID-CT (effective dose 1.33 ± 0.47 vs. 1.80 ± 0.82 mSv; all P < 0.05). CONCLUSION: Ultra-high-pitch CTPA with free-breathing technique with PCD-CT allows for superior image quality with significantly reduced radiation dose and full spectral information. With the ultra-high pitch, only PCD-CTPA enables reconstruction of iodine maps containing additional functional information.

Prospective Deployment of Deep Learning Reconstruction Facilitates Highly Accelerated Upper Abdominal MRI.

RATIONALE AND OBJECTIVES: To compare a conventional T1 volumetric interpolated breath-hold examination (VIBE) with SPectral Attenuated Inversion Recovery (SPAIR) fat saturation and a deep learning (DL)-reconstructed accelerated VIBE sequence with SPAIR fat saturation achieving a 50 % reduction in breath-hold duration (hereafter, VIBE-SPAIRDL) in terms of image quality and diagnostic confidence. MATERIALS AND METHODS: This prospective study enrolled consecutive patients referred for upper abdominal MRI from November 2023 to December 2023 at a single tertiary center. Patients underwent upper abdominal MRI with acquisition of non-contrast and gadobutrol-enhanced conventional VIBE-SPAIR (fourfold acceleration, acquisition time 16 s) and VIBE-SPAIRDL (sixfold acceleration, acquisition time 8 s) on a 1.5 T scanner. Image analysis was performed by four readers, evaluating homogeneity of fat suppression, perceived signal-to-noise ratio (SNR), edge sharpness, artifact level, lesion detectability and diagnostic confidence. A statistical power analysis for patient sample size estimation was performed. Image quality parameters were compared by a repeated measures analysis of variance, and interreader agreement was assessed using Fleiss' κ. RESULTS: Among 450 consecutive patients, 45 patients were evaluated (mean age, 60 years ± 15 [SD]; 27 men, 18 women). VIBE-SPAIRDL acquisition demonstrated superior SNR (P < 0.001), edge sharpness (P < 0.001), and reduced artifacts (P < 0.001) with substantial to almost perfect interreader agreement for non-contrast (κ: 0.70-0.91) and gadobutrol-enhanced MRI (κ: 0.68-0.87). No evidence of a difference was found between conventional VIBE-SPAIR and VIBE-SPAIRDL regarding homogeneity of fat suppression, lesion detectability, or diagnostic confidence (all P > 0.05). CONCLUSION: Deep learning reconstruction of VIBE-SPAIR facilitated a reduction of breath-hold duration by half, while reducing artifacts and improving image quality. SUMMARY: Deep learning reconstruction of prospectively accelerated T1 volumetric interpolated breath-hold examination for upper abdominal MRI enabled a 50 % reduction in breath-hold time with superior image quality. KEY RESULTS: 1) In a prospective analysis of 45 patients referred for upper abdominal MRI, accelerated deep learning (DL)-reconstructed VIBE images with spectral fat saturation (SPAIR) showed better overall image quality, with better perceived signal-to-noise ratio and less artifacts (all P < 0.001), despite a 50 % reduction in acquisition time compared to conventional VIBE. 2) No evidence of a difference was found between conventional VIBE-SPAIR and accelerated VIBE-SPAIRDL regarding lesion detectability or diagnostic confidence.

Right ventricular-pulmonary arterial coupling in patients with first acute myocardial infarction: An emerging post-revascularization triage tool.

BACKGROUND: Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling, studied in chronic RV pressure overload syndromes. However, its prognostic utility in patients with acute myocardial infarction (AMI) that may cause acute RV pressure overload remains unexplored. OBJECTIVES: To determine predictors of RV-PA uncoupling in patients with first AMI and examine whether it could improve risk stratification for cardiovascular in-hospital mortality after revascularization. METHODS: Three-hundred consecutive patients with first AMI were prospectively studied (age 61.2±11.8, 24% females). An echocardiogram was performed 24 hours after successful revascularization and TAPSE/PASP was evaluated. Cardiovascular in-hospital mortality was recorded. RESULTS: The optimal cutoff value of TAPSE/PASP to determine cardiovascular in-hospital mortality was 0.49 mm/mmHg. RV-PA uncoupling was considered for patients with TAPSE/PASP ≤0.49 mm/mmHg. Left ventricular ejection fraction (LVEF) was independently associated with RV-PA uncoupling. A total of 23 (7.7%) patients died in-hospital despite successful revascularization. TAPSE/PASP was independently associated with in-hospital mortality, after adjustment for Global Registry of Cardiovascular Events (GRACE) risk score and LVEF (Odds Ratio 0.14, 95% Confidence Intervals [0.03-0.56], P-value 0.007). The prognostic value of a baseline model including GRACE risk score and NT-pro-BNP (χ2 26.55) was significantly improved by adding LVEF ≤40 % (χ2 44.71, P-value <0.001), TAPSE ≤17 mm (χ2 75.42, P-value <0.001) and TAPSE/PASP ≤0.49 mm/mmHg (χ2 101.74, P-value <0.001) for predicting cardiovascular in-hospital mortality. CONCLUSIONS: RV-PA uncoupling, assessed by echocardiographic TAPSE/PASP ≤0.49 mm/mmHg 24 hours after revascularization, may improve risk stratification for cardiovascular in-hospital mortality post first AMI.

Incidence and Prognostic Factors of Radial Artery Occlusion in Transradial Coronary Catheterization.

Background/Objectives: Radial artery occlusion (RAO) is the most common complication of transradial coronary catheterization. In this study, we aimed to evaluate the incidence of RAO and identify the risk factors that predispose patients to it. Methods: We conducted an investigator-initiated, prospective, multicenter, open-label study involving 1357 patients who underwent cardiac catheterization via the transradial route for angiography and/or a percutaneous coronary intervention (PCI). Univariate and multivariate logistic regression analyses were performed to identify potential predictors of RAO occurrence. Additionally, a subgroup analysis only for patients undergoing PCIs was performed. Results: The incidence of RAO was 9.5% overall, 10.6% in the angiography-only group and 6.2% in the PCI group. Independent predictors of RAO were as follows: (i) the female gender (aOR = 1.72 (1.05-2.83)), (ii) access site cross-over (aOR = 4.33 (1.02-18.39)), (iii) increased total time of the sheath in the artery (aOR = 1.01 (1.00-1.02)), (iv) radial artery spasms (aOR = 2.47 (1.40-4.36)), (v) the presence of a hematoma (aOR = 2.28 (1.28-4.06)), (vi) post-catheterization dabigatran use (aOR = 5.15 (1.29-20.55)), (vii) manual hemostasis (aOR = 1.94 (1.01-3.72)) and (viii) numbness at radial artery ultrasound (aOR = 8.25 (1.70-40)). Contrariwise, two variables were independently associated with increased odds for radial artery patency (RAP): (i) PCI performance (aOR = 0.19 (0.06-0.63)), and (ii) a higher dosage of intravenous heparin per patient weight (aOR = 0.98 (0.96-0.99)), particularly, a dosage of >50 IU/kg (aOR = 0.56 (0.31-1.00)). In the PCI subgroup, independent predictors of RAO were as follows: (i) radial artery spasms (aOR = 4.48 (1.42-14.16)), (ii) the use of intra-arterial nitroglycerin as a vasodilator (aOR = 7.40 (1.67-32.79)) and (iii) the presence of symptoms at echo (aOR = 3.80 (1.46-9.87)), either pain (aOR = 2.93 (1.05-8.15)) or numbness (aOR = 4.66 (1.17-18.57)). On the other hand, the use of intra-arterial verapamil as a vasodilator (aOR = 0.17 (0.04-0.76)) was independently associated with a greater frequency of RAP. Conclusions: The incidence of RAO in an unselected, all-comers European population after transradial coronary catheterization for angiography and/or PCIs is similar to that reported in the international literature. Several RAO prognostic factors have been confirmed, and new ones are described. The female gender, radial artery trauma and manual hemostasis are the strongest predictors of RAO. Our results could help in the future identification of patients at higher risk of RAO, for whom less invasive diagnostic procedures maybe preferred, if possible.

Prognostic Impact of Body Mass Index in Atrial Fibrillation.

Background/Objectives: Contradictory results have been reported regarding the influence of obesity on the prognosis of atrial fibrillation (AF). The present study aimed to explore the potential association of body mass index (BMI) with the clinical outcomes of hospitalized patients with AF. Methods: In this retrospective, post hoc analysis of the MISOAC-AF randomized trial, 1113 AF patients were included and stratified as the following: underweight (BMI < 18 kg/m2), normal weight (BMI 18-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). The primary outcome was all-cause mortality; the secondary composite outcome was any hospitalization related to AF, heart failure (HF), or stroke. Cox regression analysis, survival analysis, and spline curve models were utilized. Results: Of the patients (median age: 76 years (IQR: 13), male: 54.6%), the majority were overweight (41.4%), followed by obese (33%), normal weight (24%), and underweight (1.6%). During a median 31-month follow-up, 436 (39.2%) patients died and 657 (59%) were hospitalized due to AF, HF, or stroke. Underweight, overweight, and obesity groups were significantly associated with an increased risk of all-cause mortality (p-values 0.02, 0.001, and <0.001, respectively), while overweight and obesity were significantly associated with the composite endpoint (p-values 0.01, <0.001, respectively) compared to normal weight. The spline curve analyses yielded that BMIs > 26.3 and > 25 were incrementally associated with all-cause mortality and the composite endpoint, respectively. A J-shaped relationship between BMI and AF prognosis was deduced. Conclusions: In conclusion, in recently hospitalized AF patients, BMI values outside the normal range were independently associated with poorer prognosis; therefore, it is essential that AF patients maintain a normal weight.

Viscoelasticity of diverse biological samples quantified by Acoustic Force Microrheology (AFMR).

In the context of soft matter and cellular mechanics, microrheology - the use of micron-sized particles to probe the frequency-dependent viscoelastic response of materials - is widely used to shed light onto the mechanics and dynamics of molecular structures. Here we present the implementation of active microrheology in an Acoustic Force Spectroscopy setup (AFMR), which combines multiplexing with the possibility of probing a wide range of forces ( ~ pN to ~nN) and frequencies (0.01-100 Hz). To demonstrate the potential of this approach, we perform active microrheology on biological samples of increasing complexity and stiffness: collagen gels, red blood cells (RBCs), and human fibroblasts, spanning a viscoelastic modulus range of five orders of magnitude. We show that AFMR can successfully quantify viscoelastic properties by probing many beads with high single-particle precision and reproducibility. Finally, we demonstrate that AFMR to map local sample heterogeneities as well as detect cellular responses to drugs.

Epigenetic predictors of species maximum life span and other life-history traits in mammals.

By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span (R = 0.89), gestation time (R = 0.96), and age at sexual maturity (R = 0.85). Our maximum life-span predictor indicates a potential innate longevity advantage for females over males in 17 mammalian species including humans. The DNAm maximum life-span predictions are not affected by caloric restriction or partial reprogramming. Genetic disruptions in the somatotropic axis such as growth hormone receptors have an impact on DNAm maximum life span only in select tissues. Cancer mortality rates show no correlation with our epigenetic estimates of life-history traits. The DNAm maximum life-span predictor does not detect variation in life span between individuals of the same species, such as between the breeds of dogs. Maximum life span is determined in part by an epigenetic signature that is an intrinsic species property and is distinct from the signatures that relate to individual mortality risk.

Strongly Inhibited Spontaneous Emission of PbS Quantum Dots Covalently Bound to 3D Silicon Photonic Band Gap Crystals.

We present an optical study of the spontaneous emission of lead sulfide (PbS) nanocrystal quantum dots in 3D photonic band gap crystals made from silicon. The nanocrystals emit in the near-infrared range to be compatible with 3D silicon nanophotonics. The nanocrystals are covalently bound to polymer brush layers that are grafted from the Si-air interfaces inside the nanostructure by using surface-initiated atom transfer radical polymerization. The presence and position of the quantum dots were previously characterized by synchrotron X-ray fluorescence tomography. We report both continuous wave emission spectra and time-resolved, time-correlated single photon counting. In time-resolved measurements, we observe that the total emission rate greatly increases when the quantum dots are transferred from suspension to the silicon nanostructures, likely due to quenching (or increased nonradiative decay) that is tentatively attributed to the presence of Cu catalysts during the synthesis. In this regime, continuous wave emission spectra are known to be proportional to the radiative rate and thus to the local density of states. In spectra normalized to those taken on flat silicon outside the crystals, we observe a broad and deep stop band that we attribute to a 3D photonic band gap with a relative bandwidth of up to 26%. The shapes of the relative emission spectra match well with the theoretical density of states spectra calculated with plane-wave expansion. The observed inhibition is 4-30 times, similar to previously reported record inhibitions, yet for coincidental reasons. Our results are relevant to applications in photochemistry, sensing, photovoltaics, and efficient miniature light sources.

mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.

Energetic stress compels cells to evolve adaptive mechanisms to adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls cell viability during glucose starvation is not well understood. Here we show that the mTORC1 effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection to mammalian cells and budding yeast under glucose starvation. Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty acid synthesis via translational repression of Acetyl-CoA Carboxylase 1 (ACC1), thereby mitigating oxidative stress. This has important relevance for cancer, as oncogene-transformed cells and glioma cells exploit the 4EBP1/2 regulation of ACC1 expression and redox balance to combat energetic stress, thereby supporting transformation and tumorigenicity in vitro and in vivo. Clinically, high EIF4EBP1 expression is associated with poor outcomes in several cancer types. Our data reveal that the mTORC1-4EBP1/2 axis provokes a metabolic switch essential for survival during glucose starvation which is exploited by transformed and tumor cells.

Diverse task-driven modeling of macaque V4 reveals functional specialization towards semantic tasks.

Responses to natural stimuli in area V4-a mid-level area of the visual ventral stream-are well predicted by features from convolutional neural networks (CNNs) trained on image classification. This result has been taken as evidence for the functional role of V4 in object classification. However, we currently do not know if and to what extent V4 plays a role in solving other computational objectives. Here, we investigated normative accounts of V4 (and V1 for comparison) by predicting macaque single-neuron responses to natural images from the representations extracted by 23 CNNs trained on different computer vision tasks including semantic, geometric, 2D, and 3D types of tasks. We found that V4 was best predicted by semantic classification features and exhibited high task selectivity, while the choice of task was less consequential to V1 performance. Consistent with traditional characterizations of V4 function that show its high-dimensional tuning to various 2D and 3D stimulus directions, we found that diverse non-semantic tasks explained aspects of V4 function that are not captured by individual semantic tasks. Nevertheless, jointly considering the features of a pair of semantic classification tasks was sufficient to yield one of our top V4 models, solidifying V4's main functional role in semantic processing and suggesting that V4's selectivity to 2D or 3D stimulus properties found by electrophysiologists can result from semantic functional goals.

Pharmacotherapy for sleep disturbances in post-traumatic stress disorder (PTSD): A network meta-analysis.

BACKGROUND: Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of pharmacotherapy on sleep outcomes among patients with PTSD. METHODS: Medline/Embase/PsychInfo/CENTRAL/clinicaltrials.gov/ICTRP, reference lists of published reviews and all included studies were searched for Randomised Controlled Trials (RCTs) examining any pharmacotherapy vs. placebo or any other drug among patients with PTSD. PRIMARY OUTCOMES: total sleep time, nightmares, sleep quality. SECONDARY OUTCOMES: sleep onset latency, number of nocturnal awakenings, time spent awake following sleep onset, dropouts due to sleep-related adverse-effects, insomnia/somnolence/vivid-dreams as adverse-effects. Pairwise and network meta-analyses were performed. RESULTS: 99 RCTs with 10,481 participants were included. Prazosin may be the most effective treatment for insomnia (SMD = -0.88, 95%CI = [-1.22;-0.54], nightmares (SMD = -0.44, 95%CI = [-0.84;-0.04]) and poor sleep quality (SMD = -0.55, 95%CI = [-1.01;-0.10]). Evidence is scarce and indicates lack of efficacy for SSRIs, Mirtazapine, z-drugs and benzodiazepines, which are widely used in daily practice. Risperidone and Quetiapine carry a high risk of causing somnolence without having a clear therapeutic benefit. Hydroxyzine, Trazodone, Nabilone, Paroxetine and MDMA-assisted psychotherapy may be promising options, but more research is needed. CONCLUSIONS: Underpowered individual comparisons and very-low to moderate confidence in effect estimates hinder the generalisability of the results. More RCTs, specifically reporting on sleep-related outcomes, are urgently needed.

Coronary angiography through the interosseous artery: expanding the limits of the wrist approach.

A 59-year-old diabetic man with a history of numerous coronary angiographies (CAs) and peripheral artery disease underwent CA due to a non-ST elevation myocardial infarction. Femoral, radial, and ulnar arteries were unpalpable.

Spliceosomal complex components are critical for adjusting the C:N balance during high-light acclimation.

Plant acclimation to an ever-changing environment is decisive for growth, reproduction, and survival. Light availability limits biomass production on both ends of the intensity spectrum. Therefore, the adjustment of plant metabolism is central to high-light (HL) acclimation, and the accumulation of photoprotective anthocyanins is commonly observed. However, mechanisms and factors regulating the HL acclimation response are less clear. Two Arabidopsis mutants of spliceosome components exhibiting a pronounced anthocyanin overaccumulation in HL were isolated from a forward genetic screen for new factors crucial for plant acclimation. Time-resolved physiological, transcriptome, and metabolome analysis revealed a vital function of the spliceosome components for rapidly adjusting gene expression and metabolism. Deficiency of INCREASED LEVEL OF POLYPLOIDY1 (ILP1), NTC-RELATED PROTEIN1 (NTR1), and PLEIOTROPIC REGULATORY LOCUS1 (PRL1) resulted in a marked overaccumulation of carbohydrates and strongly diminished amino acid biosynthesis in HL. While not generally limited in N-assimilation, ilp1, ntr1, and prl1 showed higher glutamate levels and reduced amino acid biosynthesis in HL. The comprehensive analysis reveals a function of the spliceosome components in the conditional regulation of the carbon:nitrogen balance and the accumulation of anthocyanins during HL acclimation. The importance of gene expression, metabolic regulation, and re-direction of carbon towards anthocyanin biosynthesis for HL acclimation are discussed.

The effect of repeated concussions on clinical and neurocognitive symptom severity in different contact sports.

INTRODUCTION: The potential consequences of repeated concussions in sport are well documented. However, it remains unclear whether the cumulative impact of sports-related concussions differs between different contact sports. Therefore, the aim of the current study was to investigate the cumulative effects of sports-related concussions on clinical and neurocognitive health in different contact sports. MATERIALS AND METHODS: In a prospective multicenter study, we examined 507 (74 females) active professional athletes between 18 and 40 years of age from five different contact sports (soccer, handball, American football, basketball, and ice hockey). Data collection involved concussion history, clinical symptom evaluation, neurocognitive assessment, and the collection of other sports-related information. Composite scores were built for clinical symptoms (such as neck pain and balance disturbances) and for neurocognitive symptoms (such as memory and attention impairments). RESULTS: Athletes having suffered 3+ concussions in the past showed disproportionally higher clinical symptom severity than athletes with less than three concussions across all sports. The level of clinical symptom burden in athletes with 3+ concussions indicated mild impairment. The number of past concussions did not affect neurocognitive performance. DISCUSSION: Repeated sports-related concussions appear to have a cumulative impact on clinical-but not cognitive-symptom severity. Although clinical symptom burden in athletes with 3+ concussions in the past was not alarmingly high yet in our sample, increased caution should be advised at this point. Despite few exceptions, results are similar for different contact sports, suggesting a similar multidisciplinary concussion management across all types of sport.

Catheter Ablation for Channelopathies: When Is Less More?

Ventricular fibrillation (VF) is a common cause of sudden cardiac death in patients with channelopathies, particularly in the young population. Although pharmacological treatment, cardiac sympathectomy, and implantable cardioverter defibrillators (ICD) have been the mainstay in the management of VF in patients with channelopathies, they are associated with significant adverse effects and complications, leading to poor quality of life. Given these drawbacks, catheter ablation has been proposed as a therapeutic option for patients with channelopathies. Advances in imaging techniques and modern mapping technologies have enabled increased precision in identifying arrhythmia triggers and substrate modification. This has aided our understanding of the underlying pathophysiology of ventricular arrhythmias in channelopathies, highlighting the roles of the Purkinje network and the epicardial right ventricular outflow tract in arrhythmogenesis. This review explores the role of catheter ablation in managing the most common channelopathies (Brugada syndrome, congenital long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia). While the initial results for ablation in Brugada syndrome are promising, the long-term efficacy and durability of ablation in different channelopathies require further investigation. Given the genetic and phenotypic heterogeneity of channelopathies, future studies are needed to show whether catheter ablation in patients with channelopathies is associated with a reduction in VF, and psychological distress stemming from recurrent ICD shocks, particularly relative to other available therapeutic options (e.g., quinidine in high-risk Brugada patients).

Most discriminative stimuli for functional cell type clustering.

Identifying cell types and understanding their functional properties is crucial for unraveling the mechanisms underlying perception and cognition. In the retina, functional types can be identified by carefully selected stimuli, but this requires expert domain knowledge and biases the procedure towards previously known cell types. In the visual cortex, it is still unknown what functional types exist and how to identify them. Thus, for unbiased identification of the functional cell types in retina and visual cortex, new approaches are needed. Here we propose an optimization-based clustering approach using deep predictive models to obtain functional clusters of neurons using Most Discriminative Stimuli (MDS). Our approach alternates between stimulus optimization with cluster reassignment akin to an expectation-maximization algorithm. The algorithm recovers functional clusters in mouse retina, marmoset retina and macaque visual area V4. This demonstrates that our approach can successfully find discriminative stimuli across species, stages of the visual system and recording techniques. The resulting most discriminative stimuli can be used to assign functional cell types fast and on the fly, without the need to train complex predictive models or show a large natural scene dataset, paving the way for experiments that were previously limited by experimental time. Crucially, MDS are interpretable: they visualize the distinctive stimulus patterns that most unambiguously identify a specific type of neuron.

Antidepressants compared to placebo for people with binge eating disorder: A systematic review and meta-analysis.

Binge eating disorder (BED) is the most prevalent eating disorder. Treatment options include pharmacotherapy as well as psychotherapy, with the latter recommended as a first-line option. However, the use of psychotherapeutic interventions poses several challenges. Antidepressants are easily accessible, but they lack robust evidence-base. This systematic review aims to comprehensively examine the efficacy and safety of antidepressants for the treatment of BED. Five databases were searched for randomized controlled trials (RCTs) comparing antidepressants vs. placebo in BED until 23/11/2023. Pairwise meta-analytic evaluations were performed. The primary outcomes were remission and binge eating frequency. Secondary outcomes were response to treatment, eating psychopathology, depression, anxiety, body weight, Body Mass Index (BMI), all-cause discontinuation, discontinuation due to adverse effects and total adverse events. Sixteen RCTs with a total of 984 participants were meta-analysed. Antidepressants were more effective than placebo in achieving remission (RR: 1.39, 95 % CI: 1.04 to 1.86) and in reducing binge eating episodes (SMD: -0.29, 95 % CI: -0.51 to -0.06). Similarly, in the secondary outcomes of response and depression, antidepressants demonstrated superiority over placebo. Antidepressants appear to be effective in reducing symptoms of BED. Small samples and effect sizes hinder the generalizability and clinical utility of these results. There is a lack of follow-up findings regarding the maintenance of effects. There is a pressing need for more RCTs examining antidepressants and other types of pharmacotherapy. Future research should include larger number of participants and increase the duration of follow-up.

Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.