Studies of the Energy Dependence of Diboson Polarization Fractions and the Radiation-Amplitude-Zero Effect in WZ Production with the ATLAS Detector.

This Letter presents the first study of the energy dependence of diboson polarization fractions in WZ→ℓνℓ^{'}ℓ^{'}(ℓ,ℓ^{'}=e,µ) production. The dataset used corresponds to an integrated luminosity of 140 fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector. Two fiducial regions with an enhanced presence of events featuring two longitudinally polarized bosons are defined. A nonzero fraction of events with two longitudinally polarized bosons is measured with an observed significance of 5.3 standard deviations in the region with 100200 GeV, where p_{T}^{Z} is the transverse momentum of the Z boson. This Letter also reports the first study of the radiation-amplitude-zero effect. Events with two transversely polarized bosons are analyzed for the ΔY(ℓ_{W}Z) and ΔY(WZ) distributions defined respectively as the rapidity difference between the lepton from the W boson decay and the Z boson and the rapidity difference between the W boson and the Z boson. Significant suppression of events near zero is observed in both distributions. Unfolded ΔY(ℓ_{W}Z) and ΔY(WZ) distributions are also measured and compared to theoretical predictions.

Combination of Searches for Higgs Boson Pair Production in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

This Letter presents results from a combination of searches for Higgs boson pair production using 126-140 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.4 assuming no Higgs boson pair production. Constraints on the Higgs boson self-coupling modifier κ_{λ}=λ_{HHH}/λ_{HHH}^{SM}, and the quartic HHVV coupling modifier κ_{2V}=g_{HHVV}/g_{HHVV}^{SM}, are derived individually, fixing the other parameter to its SM value. The observed 95% CL intervals are -1.2<κ_{λ}<7.2 and 0.6<κ_{2V}<1.5, respectively, while the expected intervals are -1.6<κ_{λ}<7.2 and 0.4<κ_{2V}<1.6 in the SM case. Constraints obtained for several interaction parameters within Higgs effective field theory are the strongest to date, offering insights into potential deviations from SM predictions.

Computed tomography radiomics-based cross-sectional detection of mandibular osteoradionecrosis in head and neck cancer survivors.

Purpose: This study aims to identify radiomic features extracted from contrast-enhanced CT scans that differentiate osteoradionecrosis (ORN) from normal mandibular bone in patients with head and neck cancer (HNC) treated with radiotherapy (RT). Materials and Methods: Contrast-enhanced CT (CECT) images were collected for 150 patients (80% train, 20% test) with confirmed ORN diagnosis at The University of Texas MD Anderson Cancer Center between 2008 and 2018. Using PyRadiomics, radiomic features were extracted from manually segmented ORN regions and the corresponding automated control regions, the later defined as the contralateral healthy mandible region. A subset of pre-selected features was obtained based on correlation analysis (r > 0.95) and used to train a Random Forest (RF) classifier with Recursive Feature Elimination. Model explainability SHapley Additive exPlanations (SHAP) analysis was performed on the 20 most important features identified by the trained RF classifier. Results: From a total of 1316 radiomic features extracted, 810 features were excluded due to high collinearity. From a set of 506 pre-selected radiomic features, the optimal subset resulting on the best discriminative accuracy of the RF classifier consisted of 67 features. The RF classifier was well calibrated (Log Loss 0.296, ECE 0.125) and achieved an accuracy of 88% and a ROC AUC of 0.96. The SHAP analysis revealed that higher values of Wavelet-LLH First-order Mean and Median were associated with ORN of the jaw (ORNJ). Conversely, higher Exponential GLDM Dependence Entropy and lower Square First-order Kurtosis were more characteristic of normal mandibular tissue. Conclusion: This study successfully developed a CECT-based radiomics model for differentiating ORNJ from healthy mandibular tissue in HNC patients after RT. Future work will focus on the detection of subclinical ORNJ regions to guide earlier interventions.

Frailty and Long-Term Mortality Following Emergency Laparotomy: A Comparison Between the 11-Item and 5-Item Modified Frailty Indices.

INTRODUCTION: Emergency laparotomy (EL) is a high-risk operation which is increasingly performed on an aging patient population. Objective frailty assessment using a validated index has the potential to improve preoperative risk stratification. This study aimed to assess the correlation between frailty and long-term mortality and morbidity outcomes for older EL patients. Secondary aims were to compare the 11-item and shortened five-item modified frailty indices (mFIs) in terms of value and predictive validity. METHODS: A prospective multicenter observational study of patients aged ≥55 y undergoing EL was conducted across five hospitals in New Zealand between 2017 and 2022. Frailty was measured using the 11-item and abbreviated five-item mFIs. Multivariable logistic regression was used to determine whether frailty was independently associated with one-year postoperative mortality and other morbidity outcomes. Correlation between the two frailty indices were assessed with the Spearman's correlation coefficient (P). RESULTS: Frailty assessments were performed in 861 participants, with the prevalence being 18.7% and 29.8% using the 11-item and five-item mFIs, respectively. Both frailty indices demonstrated similar associations with one-year mortality (two-fold increased risk), major complications, admission to intensive care unit, rehabilitation, and 30-d readmission. The 11-item mFI demonstrated a greater association with early mortality (four-fold increased risk), reoperations, and increased length of stay compared with the five-item frailty index. Spearman P was 0.6 (P < 0.001). CONCLUSIONS: Frailty, as identified by the 11-item and five-item mFIs, was associated with one-year mortality and other important morbidity outcomes for older EL patients. These forms of frailty assessment provide important information that may aid in risk assessment and patient-centered decision-making.

Laxative Properties of Microencapsulated Oleic Acid Delivered to the Distal Small Intestine in Patients with Constipation after Bariatric Surgery or Treatment with Glucagon-Like- Peptide 1 Analogues.

BACKGROUND: Constipation is prevalent after bariatric surgery and glucagon-like-peptide 1 (GLP-1) analogues. Increasing fat content in the distal small intestine and colon can enhance colonic peristalsis, potentially alleviating symptoms of constipation. AIM: We investigated whether oleic acid can ameliorate constipation in patients undergoing bariatric surgery or receiving GLP-1 analogues. METHODOLOGY: Fourteen adults with chronic constipation according to Rome IV criteria following bariatric surgery or GLP-1 analogues were on stable treatment for constipation for more than 4 weeks. This randomized double-blind crossover trial compared microcapsules containing 21.25 g of oleic acid delivered in the distal small intestine or the stomach. The primary outcome was changed in the number of bowel motions over 24 h. Exploratory endpoints included alterations in straining, diarrhoea, faecal leakage over 24 h and hunger, fullness, nausea and calorie intake for the 3 h after ingesting the microcapsules. FINDINGS: Receiving oleic acid into the distal small intestine increased number of bowel movements per day (2.5 vs 1.1, p = 0.009) and caused softer stool consistency (p = 0.03). 9/14 of the control group passed motions and 13/14 of the intervention group passed motions in 24 h (p = 0.059). No significant differences were observed in straining (p = 0.65), rapid bowel movements (p = 0.08), accidental leakage (p = 0.32), hunger, fullness, nausea or food intake between the groups (all p > 0.05). There were no disparities in safety profile between groups. CONCLUSION: Microcapsules containing oleic acid delivered to the distal small intestine appear to be a safe and effective relief from chronic constipation in patients undergoing bariatric surgery and/or receiving GLP-1 analogues.

Frailty using the Clinical Frailty Scale to predict short- and long-term adverse outcomes following emergency laparotomy: meta-analysis.

BACKGROUND: Emergency laparotomy has high morbidity and mortality rates. Frailty assessment remains underutilized in this setting, in part due to time constraints and feasibility. The Clinical Frailty Scale has been identified as the most appropriate tool for frailty assessment in emergency laparotomy patients and is recommended for all older patients undergoing emergency laparotomy. The prognostic impact of measured frailty using the Clinical Frailty Scale on short- and long-term mortality and morbidity rates remains to be determined. METHODS: Observational cohort studies were identified by systematically searching Medline, Embase, Scopus and CENTRAL databases up to February 2024, comparing outcomes following emergency laparotomy for frail and non-frail participants defined according to the Clinical Frailty Scale. The primary outcomes were short- and long-term mortality rates. A random-effects model was created with pooling of effect estimates and a separate narrative synthesis was created. Risk of bias was assessed. RESULTS: Twelve articles comprising 5704 patients were included. Frailty prevalence was 25% in all patients and 32% in older adults (age ≥55 years). Older patients with frailty had a significantly greater risk of postoperative death (30-day mortality rate OR 3.84, 95% c.i. 2.90 to 5.09, 1-year mortality rate OR 3.03, 95% c.i. 2.17 to 4.23). Meta-regression revealed that variations in cut-off values to define frailty did not significantly affect the association with frailty and 30-day mortality rate. Frailty was associated with higher rates of major complications (OR 1.93, 95% c.i. 1.27 to 2.93) and discharge to an increased level of care. CONCLUSION: Frailty is significantly correlated with short- and long-term mortality rates following emergency laparotomy, as well as an adverse morbidity rate and functional outcomes. Identifying frailty using the Clinical Frailty Scale may aid in patient-centred decision-making and implementation of tailored care strategies for these 'high-risk' patients, with the aim of reducing adverse outcomes following emergency laparotomy.

Deep Learning Algorithms for the Detection of Suspicious Pigmented Skin Lesions in Primary Care Settings: A Systematic Review and Meta-Analysis.

Early detection of suspicious pigmented skin lesions is crucial for improving the outcomes and survival rates of skin cancers. However, the accuracy of clinical diagnosis by primary care physicians (PCPs) is suboptimal, leading to unnecessary referrals and biopsies. In recent years, deep learning (DL) algorithms have shown promising results in the automated detection and classification of skin lesions. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of DL algorithms for the detection of suspicious pigmented skin lesions in primary care settings. A comprehensive literature search was conducted using electronic databases, including PubMed, Scopus, IEEE Xplore, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Data from eligible studies were extracted, including study characteristics, sample size, algorithm type, sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and receiver operating characteristic curve analysis. Three studies were included. The results showed that DL algorithms had a high sensitivity (90%, 95% CI: 90-91%) and specificity (85%, 95% CI: 84-86%) for detecting suspicious pigmented skin lesions in primary care settings. Significant heterogeneity was observed in both sensitivity (p = 0.0062, I2 = 80.3%) and specificity (p < 0.001, I2 = 98.8%). The analysis of DOR and PLR further demonstrated the strong diagnostic performance of DL algorithms. The DOR was 26.39, indicating a strong overall diagnostic performance of DL algorithms. The PLR was 4.30, highlighting the ability of these algorithms to influence diagnostic outcomes positively. The NLR was 0.16, indicating that a negative test result decreased the odds of misdiagnosis. The area under the curve of DL algorithms was 0.95, indicating excellent discriminative ability in distinguishing between benign and malignant pigmented skin lesions. DL algorithms have the potential to significantly improve the detection of suspicious pigmented skin lesions in primary care settings. Our analysis showed that DL exhibited promising performance in the early detection of suspicious pigmented skin lesions. However, further studies are needed.

Statistical Combination of ATLAS Run 2 Searches for Charginos and Neutralinos at the LHC.

Statistical combinations of searches for charginos and neutralinos using various decay channels are performed using 139 fb^{-1} of pp collision data at sqrt[s]=13 TeV with the ATLAS detector at the Large Hadron Collider. Searches targeting pure-wino chargino pair production, pure-wino chargino-neutralino production, or Higgsino production decaying via standard model W, Z, or h bosons are combined to extend the mass reach to the produced supersymmetric particles by 30-100 GeV. The depth of the sensitivity of the original searches is also improved by the combinations, lowering the 95% C.L. cross-section upper limits by 15%-40%.

Evaluation of the Transfemoral Bone-Implant Interface Properties Using Vibration Analysis.

Evaluating the bone-implant interface (BII) properties of osseointegrated transfemoral (TFA) implants is important for early failure detection and prescribing loads during rehabilitation. The objective of this work is to derive and validate a 1D finite element (FE) model of the Osseointegrated Prosthetic Limb (OPL) TFA system that can: (1) model its dynamic behaviour and (2) extract the BII properties. The model was validated by: (1) comparing the 1D FE formulation to the analytical and 3D FE solutions for a simplified cylinder, (2) comparing the vibration modes of the actual TFA geometry using 1D and 3D FE models, and (3) evaluating the BII properties for three extreme conditions (LOW, INTERMEDIATE, and HIGH) generated using 3D FE and experimental (where the implant was embedded, using different adhesives, in synthetic femurs) signals for additional validation. The modes predicted by the 1D FE model converged to the analytical and the 3D FE solutions for the cylinder. The 1D model also matched the 3D FE solution with a maximum frequency difference of 2.02% for the TFA geometry. Finally, the 1D model extracted the BII stiffness and the system's damping properties for the three conditions generated using the 3D FE simulations and the experimental INTERMEDIATE and HIGH signals. The agreement between the 1D FE and the 3D FE solutions for the TFA geometry indicates that the 1D model captures the system's dynamic behaviour. Distinguishing between the different BII conditions demonstrates the 1D model's potential use for the non-invasive clinical evaluation of the TFA BII properties.

Ultrasound-Guided Versus Palpation-Guided Techniques to Achieve Vascular Access in Children Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Pediatric heart surgery is a vital therapeutic option for congenital heart disease, which is one of the most prevalent causes of death in children. Arterial cannulation (AC) and central venous catheter (CVC) are required in pediatric cardiac surgery for continuous monitoring of the central venous pressure (CVP), replacement of fluid or blood products, close hemodynamic monitoring, and frequent sampling for arterial blood gases (ABG). A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) retrieved from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. Risk ratio (RR) was used to report dichotomous outcomes, and mean difference (MD) was used to report continuous outcomes, both with a 95% confidence interval (CI) using the random-effects model. Thirteen RCTs with 1060 children were included. Regarding arterial cannulation, the ultrasound-guided technique (US) was associated with a statistically significant increase in successful cannulation [RR: 1.31 with 95% CI (1.10, 1.56), P < 0.0001], and first-attempt success [RR: 1.88 with 95% CI (1.35, 2.63), P < 0.0001]. However, US was not associated with any statistically significant difference in venous cannulation in both outcomes with [RR: 1.13 with 95% CI (0.98, 1.30), P = 0.10], [RR: 1.53 with 95% CI (0.86, 2.71), P = 0.15] respectively. Moreover, US was associated with a statistically significant decrease in the number of attempts either in arterial cannulation with [MD: - 0.73 with 95% CI (- 1.00, - 0.46), P < 0.0001] or in venous cannulation with [MD: - 1.34 with 95% CI (- 2.55, - 0.12), P = 0.03], and the time of attempted cannulation also either in arterial cannulation with [MD: - 2.27 with 95% CI (- 3.38, - 1.16), P < 0.0001] or in venous cannulation with [MD: - 4.13 with 95% CI (- 7.06, - 1.19), P < 0.0001]. US guidance improves successful cannulation rates and first-attempt success in arterial access and reduces the number of attempts and procedural time for arterial and venous access. It was also associated with a lower incidence of complications and procedure failure, particularly in arterial access. However, it was associated with a higher incidence of venous puncture.

Azimuthal Angle Correlations of Muons Produced via Heavy-Flavor Decays in 5.02 TeV Pb+Pb and pp Collisions with the ATLAS Detector.

Angular correlations between heavy quarks provide a unique probe of the quark-gluon plasma created in ultrarelativistic heavy-ion collisions. Results are presented of a measurement of the azimuthal angle correlations between muons originating from semileptonic decays of heavy quarks produced in 5.02 TeV Pb+Pb and pp collisions at the LHC. The muons are measured with transverse momenta and pseudorapidities satisfying p_{T}^{µ}>4 GeV and |η^{µ}|<2.4, respectively. The distributions of azimuthal angle separation Δϕ for muon pairs having pseudorapidity separation |Δη|>0.8, are measured in different Pb+Pb centrality intervals and compared to the same distribution measured in pp collisions at the same center-of-mass energy. Results are presented separately for muon pairs with opposite-sign charges, same-sign charges, and all pairs. A clear peak is observed in all Δϕ distributions at Δϕ∼π, consistent with the parent heavy-quark pairs being produced via hard-scattering processes. The widths of that peak, characterized using Cauchy-Lorentz fits to the Δϕ distributions, are found to not vary significantly as a function of Pb+Pb collision centrality and are similar for pp and Pb+Pb collisions. This observation will provide important constraints on theoretical descriptions of heavy-quark interactions with the quark-gluon plasma.

Impact of pre-existing mesh at the hiatus at revisional hiatal hernia surgery.

Recurrence after laparoscopic hiatus hernia repair (LHR) is high, with few symptomatic patients undergoing redo LHR. Morbidity is higher in redo surgery compared with the primary operation. Tens of studies have explored the safety of redoing LHR. However, the impact of existing mesh on operative risk is rarely examined. We aim to assess the impact of mesh at the hiatus on the safety of redo LHR. This was a cohort study examining redo LHR patients from a prospectively maintained database from January 2002 to December 2023. The primary outcome was intra-/postoperative complications. Follow-up was extracted from clinical records. Predictors of complications were assessed using univariable and multivariable logistic regression analyses. Redo LHR was performed in 100 patients; 22 had previous mesh. One encountered mortality with 23 complications. Five patients had absorbable mesh, with the remainder nonabsorbable. Overall complications were significantly higher with mesh at nine (40.9%) compared to no mesh redo at 14 (17.9%), P = 0.023. There was no difference in rates of visceral injury with mesh at four (18.2%) and no mesh at six (7.7%), P = 0.22. The median follow-up was 7 months; there was no difference in reflux rates (P = 0.70) but higher rates of dysphagia (P = 0.010). Higher overall complications were noted in patients with previous hiatal mesh repair at the time of LHR. However, major visceral complications were similar regardless of mesh use. Mesh at the hiatus should not be a deterrent for reoperative hiatus surgery.

Search for Nearly Mass-Degenerate Higgsinos Using Low-Momentum Mildly Displaced Tracks in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

Higgsinos with masses near the electroweak scale can solve the hierarchy problem and provide a dark matter candidate, while detecting them at the LHC remains challenging if their mass splitting is O(1 GeV). This Letter presents a novel search for nearly mass-degenerate Higgsinos in events with an energetic jet, missing transverse momentum, and a low-momentum track with a significant transverse impact parameter using 140 fb^{-1} of proton-proton collision data at sqrt[s]=13 TeV collected by the ATLAS experiment. For the first time since LEP, a range of mass splittings between the lightest charged and neutral Higgsinos from 0.3 to 0.9 GeV is excluded at 95% confidence level, with a maximum reach of approximately 170 GeV in the Higgsino mass.

Combination of Searches for Resonant Higgs Boson Pair Production Using pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

A combination of searches for a new resonance decaying into a Higgs boson pair is presented, using up to 139 fb^{-1} of pp collision data at sqrt[s]=13 TeV recorded with the ATLAS detector at the LHC. The combination includes searches performed in three decay channels: bb[over ¯]bb[over ¯], bb[over ¯]τ^{+}τ^{-}, and bb[over ¯]γγ. No excess above the expected Standard Model background is observed and upper limits are set at the 95% confidence level on the production cross section of Higgs boson pairs originating from the decay of a narrow scalar resonance with mass in the range 251 GeV-5 TeV. The observed (expected) limits are in the range 0.96-600 fb (1.2-390 fb). The limits are interpreted in the type-I two-Higgs-doublet model and the minimal supersymmetric standard model, and constrain parameter space not previously excluded by other searches.

Exploring structural phase transition, electronic and optical characteristics of optoelectronic phosphides XSiP2 (X = Mg, Cd, and Zn) through First principle computation.

CONTEXT: The present study reports the properties of pressure-induced phase transition, electronic and optical of phosphides XSiP2 under pressure in chalcopyrite, sodium chloride (rock salt), and Wurtzite phases. The study shows the chalcopyrite phase as the most stable phase among the other studied phases. The obtained structural parameters in the chalcopyrite and rock-salt phases reasonably agree with the literature. The computed band structures revealed a semiconductor behavior in chalcopyrite structure and metallic behavior for rock- salt and wurtzite structures. In the energy range of 0 to 30 eV, optical parameters such as the real and imaginary parts of the dielectric constant, refractive index, and reflectivity are calculated and compared with existing data. Our optical properties findings are predictive for the rock-salt and wurtzite phases. Since no results are available in the literature, these results may serve as references for other theoretical and experimental studies. METHOD: The calculations are performed by employing the "full-potential linearized augmented plane wave (FP-LAPW) method within density functional theory (DFT)."

A multifaceted suite of metrics for comparative myoelectric prosthesis controller research.

Upper limb robotic (myoelectric) prostheses are technologically advanced, but challenging to use. In response, substantial research is being done to develop person-specific prosthesis controllers that can predict a user's intended movements. Most studies that test and compare new controllers rely on simple assessment measures such as task scores (e.g., number of objects moved across a barrier) or duration-based measures (e.g., overall task completion time). These assessment measures, however, fail to capture valuable details about: the quality of device arm movements; whether these movements match users' intentions; the timing of specific wrist and hand control functions; and users' opinions regarding overall device reliability and controller training requirements. In this work, we present a comprehensive and novel suite of myoelectric prosthesis control evaluation metrics that better facilitates analysis of device movement details-spanning measures of task performance, control characteristics, and user experience. As a case example of their use and research viability, we applied these metrics in real-time control experimentation. Here, eight participants without upper limb impairment compared device control offered by a deep learning-based controller (recurrent convolutional neural network-based classification with transfer learning, or RCNN-TL) to that of a commonly used controller (linear discriminant analysis, or LDA). The participants wore a simulated prosthesis and performed complex functional tasks across multiple limb positions. Analysis resulting from our suite of metrics identified 16 instances of a user-facing problem known as the "limb position effect". We determined that RCNN-TL performed the same as or significantly better than LDA in four such problem instances. We also confirmed that transfer learning can minimize user training burden. Overall, this study contributes a multifaceted new suite of control evaluation metrics, along with a guide to their application, for use in research and testing of myoelectric controllers today, and potentially for use in broader rehabilitation technologies of the future.

A Cluster Analysis of Neuropsychological Impairment in Borderline Personality Disorder: Identifying a Neurocognitive Subtype Linked to Attention Deficit Hyperactivity Disorder.

INTRODUCTION: Cognitive impairment associated with borderline personality disorder (BPD) has been consistently demonstrated. However, a specific neuropsychological profile has not yet been established for this disorder, maybe due to the heterogeneity of BPD. The aim of this work is the search for distinct neuropsychological subtypes among patients with BPD and for the association of neuropsychological subgroups with specific clinical characteristics. METHODOLOGY: One hundred fifteen patients with BPD diagnosis received an extensive neuropsychological evaluation assessing attentional, memory and executive functions indexes. For subtyping strategies, a cluster analysis of neuropsychological BPD distribution was performed. Central clinical dimensions of BPD were measured and analysed in relation with the obtained neuropsychological clusters. RESULTS: Two clusters were found: Cluster 1 showed a significantly lower score on the working memory index, and Cluster 2 had significantly worse overall executive performance, response inhibition and planning abilities. Patients in the neurocognitive Cluster 2 showed significantly higher clinical deficits of attention as measured with subscales of the CAARS attention deficit hyperactivity disorder (ADHD) index (F = 2.549, p < 0.005, d = 11.49). CONCLUSIONS: Two neuropsychological clusters of patients were found in the BPD sample: Cluster 1 patients showed greater impairment in working memory, while Cluster 2 patients had greater deficits of executive functioning, particularly for response inhibition and planning. In addition, BPD patients with greater executive deficits presented greater levels of ADHD clinical features. These findings might also facilitate earlier diagnosis of severe BPD patient profiles and to establish more personalized treatment based on neurocognitive stimulation.

Efficacy and safety of aldafermin in non-alcoholic steatohepatitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced subtype of non-alcoholic fatty liver disease (NAFLD). NASH prevalence is increasing exponentially and carries a high risk for disease progression, cirrhosis, and liver-related mortality. Aldafermin, a fibroblast growth factor 19 (FGF19) analog, is one of the evolving therapeutic agents with the potential to regulate multiple pathways involved in the pathogenesis of NASH. We aimed to investigate the efficacy and safety of aldafermin in patients with NASH. METHODS: PubMed, Scopus, Cochrane Library, and Web of Science were searched till November 2023 to identify eligible randomized controlled trials (RCTs). Continuous data were pooled as mean difference (MD), while dichotomous data were pooled as risk ratios (RR) with a 95 % confidence interval. A subgroup meta-analysis was conducted to evaluate the efficacy of the two doses (1 mg and 3 mg) of aldafermin. RESULTS: Four RCTs with a total of 491 patients were included. Aldafermin showed a dose-dependent improvement in the ≥30 % reduction in the liver fat content (RR: 2.16, 95 % CI [1.41 to 3.32]) and (RR: 5.00, 95 % CI [1.34 to 18.64]), alanine aminotransferase levels (MD: -19.79, 95 % CI [-30.28 to -9.3]) and (MD: -21.91, 95 % CI [-29.62 to -14.21]), aspartate aminotransferase levels (MD: -11.79, 95 % CI [-18.06 to -5.51]) and (MD: -13.9, 95 % CI [-18.59 to -9.21]), and enhanced liver fibrosis score (ELF) (MD: -0.13, 95 % CI [-0.29 to 0.02]) and (MD: -0.33, 95 % CI [-0.50 to -0.17]), in the 1 mg and 3 mg subgroups respectively. No significant differences were detected in the aldafermin group regarding histologic endpoints, lipid profile, metabolic parameters, and overall adverse effects, except for the increased occurrence of diarrhea in the aldafermin 3 mg subgroup. CONCLUSION: Aldafermin is a promising well-tolerated therapeutic agent for NASH with evidence supporting its ability to reduce liver fat content, fibrosis serum biomarkers, and liver enzymes. However, its effectiveness in improving histologic fibrosis, while showing numerical trends, still lacks statistical significance. Larger and longer NASH trials are warranted to enhance the robustness of the evidence.

Diagnostic accuracy of ePOS score in predicting DNR labeling after ICU admission: A prospective observational study (ePOS-DNR).

Background: Resuscitation can sometimes be futile and making a do-not-resuscitate (DNR) decision is in the best interest of the patient. The electronic poor outcome screening (ePOS) score was developed to predict 6-month poor outcomes of critically ill patients. We explored the diagnostic accuracy of the ePOS score in predicting DNR decisions in the intensive care unit (ICU). Methods: This study was conducted at the ICU of a tertiary referral hospital in Saudi Arabia between March and May 2023. Prospectively, we calculated ePOS scores for all eligible consecutive admissions after 48 h in the ICU and recorded the DNR orders. The ability of the score to predict DNR was explored using logistic regression. Youden's ideal cut-off value was calculated using the DeLong method, and different diagnostic accuracy measures were generated with corresponding 95 % confidence intervals (CIs). Results: We enrolled 857 patients, 125 received a DNR order and 732 did not. The average ePOS score of DNR and non-DNR patients was 28.2±10.7 and 15.2±9.7, respectively. ePOS score, as a predictor of DNR order, had an area under receiver operator characteristic (AUROC) curve of 81.8 % (95% CI: 79.0 to 84.3, P <0.001). Youden's ideal cut-off value >17 was associated with a sensitivity of 87.2 (95% CI: 80.0 to 92.5, P <0.001), specificity of 63.9 (95% CI: 60.3 to 67.4, P <0.001), positive predictive value of 29.2 (95% CI: 24.6 to 33.8, P <0.001), negative predictive value of 96.7 (95% CI: 95.1 to 98.3, P <0.001), and diagnostic odds ratio 12.1 (95% CI: 7.0 to 20.8, P <0.001). Conclusions: In this study, the ePOS score performed well as a diagnostic test for patients who will be labeled as DNR during their ICU stay. A cut-off score >17 may help guide clinical decisions to withhold or commence resuscitative measures.