Risk Stratification Research Articles

Endoscopic management of upper non-variceal and lower gastrointestinal bleeding: Where do we stand?

Non-variceal upper gastrointestinal bleeding (GIB) remains a significant clinical challenge with a 30-day mortality of up to 11%. Peptic ulcers are the most common cause, followed by other conditions like Mallory-Weiss syndrome, Dieulafoy’s lesions, and gastric neoplasms. Treatment strategies include acid-suppressive therapy, endoscopic interventions, and surgical or radiological procedures. Endoscopic techniques such as over-the-scope clips, coagulation graspers, and endoscopic ultrasound-guided treatments have significantly improved outcomes, reducing rebleeding rates and the need for surgery. Injectable therapies, mechanical hemostasis via clips, and thermal modalities (e.g. , electrocoagulation, argon plasma coagulation) remain standard approaches for active bleeding. Newer hemostatic powders, such as TC-325, offer promising non-contact treatments, particularly in cases of refractory bleeding or malignancy. Doppler endoscopic probes aid in risk stratification by detecting residual arterial blood flow, improving the efficacy of endoscopic therapy and reducing rebleeding risks. For small bowel bleeding, endoscopic management with enteroscopy and thermal therapies remains key, though medical therapies are evolving. Lower GIB, which often involves conditions like diverticular disease and angioectasia, requires a comprehensive approach combining endoscopic, radiologic, and surgical interventions. Pharmacologic management focuses on balancing antithrombotic therapy with bleeding risks, with reversal agents playing a crucial role in life-threatening bleeding episodes. This review highlights advances in diagnostic tools and endoscopic therapies that have enhanced management outcomes for GIB across various etiologies.

Psychiatric Prognosis Following Index Suicide Attempts in Early Adolescents.

The rates of suicide and suicide attempts are rising precipitously among early adolescents aged 10 to 14 years in the US. While suicide attempts in this age group are more common and associated with lower lethality than in older age groups, very little is known about these individuals' long-term social and psychiatric outcomes. To examine the adult outcomes of individuals making index suicide attempts that came to medical attention between the ages of 10 and 14 years. This population-based cohort constitutes a subsample (n = 164) of a previously reported retrospective-prospective study examining individuals who made index suicide attempts during a 22-year period (1986-2007) in Olmsted County, Minnesota. To collect outcome measures, the medical records of all individuals were queried until March 31, 2023, comprising up to 36 years of follow-up data after the index attempt. Measures included current social, psychiatric, and mortality outcomes as well as lifetime measures of psychiatric hospitalizations and repeat suicide attempts. K-means clustering generated adult groupings based on aggregates of psychiatric hospitalizations and repeat attempts. Multivariable logistic regression identified index attempt factors associated with poor adult outcomes. Of 164 individuals aged 10 to 14 years who made index attempts (128 [78.0%] female; mean [SD] age at index attempt, 13.7 [1.1] years), 3 (1.8%) died on the index attempt. In the follow-up period, no individuals died by suicide. K-means clustering generated a 2-group solution reflecting low (120 [80%]) and high (30 [20%]) rates of adult psychopathology. While a minority of the sample belonged to the high-rate group, characterized by multiple repeat attempts and hospitalizations, the majority had favorable social indicators and fewer reattempts and hospitalizations. Poor adult outcomes were associated with being male (odds ratio, 2.44; 95% CI, 1.00-5.80; P = .04) and having a psychiatric diagnosis prior to the index attempt (odds ratio, 3.27; 95% CI, 1.42-8.07; P = .007). In this sample of early adolescents with index suicide attempts followed into adulthood, all who died by suicide did so on the index attempt. While a small number of individuals went on to develop chronic severe psychopathology, the majority demonstrated little evidence of long-term impairment. Given this discrepancy, future studies should focus on using risk stratification after index attempts to direct postvention resources toward adolescents more susceptible to poor outcomes.

Risk stratification and conservative management of women aged 25–40 years with cervical intraepithelial neoplasia grade 2(CIN2)

BackgroundCervical intraepithelial neoplasia grade 2 (CIN2) can progress to CIN3 or worse (CIN3+). Some patients diagnosed with CIN2 from a punch biopsy exhibit varied risks of occult CIN3+ in the loop electrosurgical excision procedure (LEEP) specimens following treatment, underscoring the need for risk stratification.MethodsWe conducted a retrospective observational study of 307 women aged ≤ 40 years, diagnosed with CIN2 via colposcopy-guided punch biopsy where the squamocolumnar junction was visible, and who underwent LEEP within three months. We compared the diagnoses from punch biopsies with the histology of the LEEP specimens and developed a stratified management algorithm based on identified risk factors.ResultsThe risk of CIN3+ in the LEEP specimens for women aged 25–40 years was 24.9% (including one case of cervical microinvasive squamous cell carcinoma), significantly higher than in women under 25 years in univariate analysis (24.9% vs. 7.1%, P < 0.05). Multivariate analysis revealed HPV16/18 (OR 2.61, [95% CI 1.41–4.85]) and HSIL cytology (OR 4.14, [95% CI 2.03–8.47]) as independent risk factors.ConclusionPatients aged 25–40 years with CIN2 diagnosed in punch biopsy exhibited a substantial risk of CIN3+ in LEEP specimens, warranting consideration for surgical intervention, particularly in those with HPV16/18 and HSIL cytology. Approximately 30% of CIN2 patients with HPV16/18 and ASC-US/LSIL, or other high-risk HPV types and HSIL cytology, also showed CIN3+, suggesting that treatment should be individualized considering the patient’s preferences and adherence. Conversely, the risk was low for those with HPV16/18 and normal cytology or other high-risk HPV types and ASC-US/LSIL, making conservative management a viable option.

Important aspects of the multimodal perioperative management in gynecology.

Multimodal perioperative management is an integrative, holistic approach to optimizing perioperative patient care. The aim is to accelerate postoperative recovery, minimize complications and increase patient satisfaction. This approach combines various strategies that are tailored to the individual needs of patients. A comprehensive preoperative assessment, in particular preoperative individual risk stratification and perioperative medication management, makes it possible to identify risk factors and take targeted measures. Our overview is intended to provide compact information, particularly for the preoperative setting, and to provide suggestions for practice based on the guideline-oriented summary.

Cardiac Structure, Function and Mechanics in Hypertensive Disorders of Pregnancy: A Systematic Review and Meta-Analysis.

Hypertensive disorders of pregnancy (HDP) are among the most common pregnancy complications and leading causes of maternal morbidity and mortality worldwide. This study aimed to perform the largest meta-analysis to date comparing conventional and advanced echocardiographic features in HDP against healthy pregnancy. PubMed (MEDLINE) and EMBASE were systematically searched for research articles published up to March 2024. Included studies reported at least 1 relevant echocardiographic parameter in pregnancies complicated by HDP and normotensive healthy pregnancies separately. A total of 53 studies met the inclusion criteria, comprising 7168 participants (3381 HDP and 3787 controls). Myocardial mechanics, as measured by global longitudinal strain (weighted mean difference (WMD), -2.81% [95% CI, -3.70 to -1.91]; P<0.001) and left atrial reservoir strain (WMD, -9.36% [95% CI, -12.73 to -5.99]; P<0.001), were significantly impaired in HDP compared with healthy pregnancy. Furthermore, there were prominent cardiac structural differences, with significantly greater left ventricular mass index (WMD, 12.20 [95% CI, 9.77-14.64]; P<0.001), relative wall thickness (WMD, 0.055 [95% CI, 0.04-0.07]; P<0.001), left atrial size (WMD, 2.34 cm [95% CI, 1.62-3.06]; P<0.001), and left atrial volume index (WMD, 2.38 mL/m2 [95% CI, 1.44-3.32]; P<0.001) in HDP compared with healthy pregnancy. Finally, the ratio between early mitral inflow velocity and early mitral annular velocity average was significantly greater in HDP (WMD, 1.90 [95% CI, 1.42-2.38; P<0.001), indicative of an elevated left ventricular filling pressure. This meta-analysis highlights clinically relevant differences in echocardiographic measures between HDP and healthy pregnancy. These results may enhance the utilization of echocardiography for the risk stratification and management of women with HDP. Advanced myocardial mechanics, including global longitudinal strain and left atrial reservoir strain, likely play a key role in detecting subclinical myocardial dysfunction and guidance for early intervention.

Pictorial review of bilateral adnexal lesions.

Bilateral adnexal lesions involve structures such as the ovaries, fallopian tubes, and surrounding tissues, arising from diverse etiologies, including inflammatory, infectious, neoplastic, and functional causes. Their variable presentation poses a diagnostic challenge in clinical practice, necessitating a multidisciplinary approach for accurate assessment and management. The American College of Radiology (ACR) introduced the Ovarian-Adnexal Reporting and Data System (O-RADS) as a standardized lexicon and risk stratification tool for evaluating adnexal lesions via ultrasound (US) and magnetic resonance imaging (MRI). While MRI is the most accurate modality for assessing indeterminate adnexal masses, bilateral lesions frequently present diagnostic dilemmas, particularly when they exhibit divergent O-RADS classifications or arise from different etiologies. The O-RADS system does not provide specific guidelines for bilateral lesions, requiring independent classification of each lesion, with management dictated by the highest assigned category. Certain pathologies demonstrate a propensity for bilateral involvement, underscoring the importance of recognizing their imaging characteristics and differential diagnoses. Integrating this knowledge into diagnostic reports enhances clinical decision-making and optimizes patient outcomes.

Risk stratification of node-positive early-stage cervical cancer treated with radical hysterectomy followed by chemoradiotherapy: a retrospective single-center study

BackgroundLimited data exist on the effectiveness of concurrent chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT) after radical surgery in patients with node-positive early-stage cervical cancer. This study aimed to identify prognostic factors and categorize patients into risk groups for personalized adjuvant therapy.MethodsThe study included consecutive patients with pathologically confirmed node-positive cervical cancer who underwent radical hysterectomy and lymphadenectomy followed by CRT from January 2013 to October 2024 at our institute. Patients with parametrial invasion or positive resection margins were excluded. All patients received modern volumetric-modulated arc therapy with platinum-based concurrent chemotherapy. Data on clinicopathologic features, treatment details, and oncologic outcomes were collected. Univariate and multivariate Cox regression analyses were conducted to identify factors associated with disease-free survival (DFS) and overall survival (OS). Patients were further stratified into distinct risk categories for recurrence based on identified prognostic factors.ResultsA total of 160 patients were included, with a median age of 44 years. The median number of lymph nodes retrieved was 33, and 11 patients presented with para-aortic lymph node metastasis (LNM). Over a median follow-up period of 39.7 months, 31 patients experienced disease progression, and 12 succumbed to the disease, yielding 3-year DFS and OS rates of 81.3% and 93.7%, respectively. Multivariate analysis identified non-squamous histotype (hazard ratio [HR]: 1.526, 95% confidence interval [CI]: 1.044–2.232, p = 0.029) and LNM ≥ 4 (HR: 1.521, 95% CI: 1.027–2.252, p = 0.036) as independent predictors of poorer DFS. Utilizing these prognostic factors for DFS, a risk stratification system was developed, categorizing patients into low-risk (no risk factors, n = 108) and high-intermediate risk (one or two risk factors, n = 52) groups. The high-intermediate-risk group exhibited significantly inferior DFS and OS compared to the low-risk group (3-year DFS: 67.4% versus 87.3%, HR: 1.697, 95% CI: 1.192–2.417, p = 0.002; 3-year OS: 82.5% versus 98.8%, HR: 3.577, 95% CI: 1.668–7.667, p < 0.001, respectively).ConclusionsNode-positive early-stage cervical cancer exhibits heterogeneous outcomes following radical hysterectomy and postoperative CRT. In patients with non-SCC histotype or ≥ 4 LNM, consolidation chemotherapy does not confer an additional survival benefit, indicating a need for innovative therapeutic strategies.

Cardiovascular imaging techniques for electrophysiologists.

Rapid technological advancements in noninvasive and invasive imaging including echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography have allowed for improved anatomical visualization and precise measurement of cardiac structure and function. These imaging modalities allow for evaluation of how cardiac substrate changes, such as myocardial wall thickness, fibrosis, scarring and chamber enlargement and/or dilation, have an important role in arrhythmia initiation and perpetuation. Here, we review the various imaging techniques and modalities used by clinical and basic electrophysiologists to study cardiac arrhythmia mechanisms, periprocedural planning, risk stratification and precise delivery of ablation therapy. We also review the use of artificial intelligence and machine learning to improve identification of areas for triggered activity and isthmuses in reentrant arrhythmias, which may be favorable ablation targets.

Development of a machine learning-based predictive risk model combining fatty acid metabolism and ferroptosis for immunotherapy response and prognosis in prostate cancer

Prostate cancer (PCa) remains a leading cause of cancer-related mortality, necessitating robust prognostic models and personalized therapeutic strategies. This study integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to construct a prognostic model based on genes shared between ferroptosis and fatty acid metabolism (FAM). Using the TCGA-PRAD dataset, we identified 73 differentially expressed genes (DEGs) at the intersection of ferroptosis and FAM, of which 19 were significantly associated with progression-free survival (PFS). A machine learning-based prognostic model, optimized using the Lasso + Random Survival Forest (RSF) algorithm, achieved a high C-index of 0.876 and demonstrated strong predictive accuracy (1-, 2-, and 3-year AUCs: 0.77, 0.75, and 0.78, respectively). The model, validated in the DFKZ cohort, stratified patients into high- and low-risk groups, with the high-risk group exhibiting worse PFS and higher tumor mutation burden (TMB). Functional enrichment analysis revealed distinct pathway activities, with high-risk patients showing enrichment in immune-related and proliferative pathways, while low-risk patients were enriched in metabolic pathways. Immune microenvironment analysis revealed heightened immune activity in high-risk patients, characterized by increased infiltration of CD8 + T cells, regulatory T cells, and M2 macrophages, alongside elevated TIDE scores, suggesting immune evasion and resistance to immunotherapy. In contrast, low-risk patients exhibited higher infiltration of plasma cells and neutrophils and demonstrated better responses to immune checkpoint inhibitors (ICIs). Spatial transcriptomics and scRNA-seq further elucidated the spatial distribution of model genes, highlighting the central role of macrophages in mediating risk stratification. Additionally, chemotherapy sensitivity analysis identified potential therapeutic agents, such as Erlotinib and Picolinic acid, for low-risk patients. In vitro experiments showed that overexpression of CD38 in the PC-3 cell line led to elevated lipid peroxidation (C11-BODIPY) and reactive oxygen species (ROS), suggesting increased cell ferroptosis. These findings provide a comprehensive framework for risk stratification and personalized treatment in PCa, bridging molecular mechanisms with clinical outcomes.

Predictive Modeling of Acute Respiratory Distress Syndrome Using Machine Learning: Systematic Review and Meta-Analysis.

Acute respiratory distress syndrome (ARDS) is a critical condition commonly encountered in the intensive care unit (ICU), characterized by a high incidence and substantial mortality rate. Early detection and accurate prediction of ARDS can significantly improve patient outcomes. While machine learning (ML) models are increasingly being used for ARDS prediction, there is a lack of consensus on the most effective model or methodology. This study is the first to systematically evaluate the performance of ARDS prediction models based on multiple quantitative data sources. We compare the effectiveness of ML models via a meta-analysis, revealing factors affecting performance and suggesting strategies to enhance generalization and prediction accuracy. This study aims to evaluate the performance of existing ARDS prediction models through a systematic review and meta-analysis, using metrics such as area under the receiver operating characteristic curve, sensitivity, specificity, and other relevant indicators. The findings will provide evidence-based insights to support the development of more accurate and effective ARDS prediction tools. We performed a search across 6 electronic databases for studies developing ML predictive models for ARDS, with a cutoff date of December 29, 2024. The risk of bias in these models was evaluated using the Prediction model Risk of Bias Assessment Tool. Meta-analyses and investigations into heterogeneity were carried out using Meta-DiSc software (version 1.4), developed by the Ramón y Cajal Hospital's Clinical Biostatistics team in Madrid, Spain. Furthermore, sensitivity, subgroup, and meta-regression analyses were used to explore the sources of heterogeneity more comprehensively. ML models achieved a pooled area under the receiver operating characteristic curve of 0.7407 for ARDS. The additional metrics were as follows: sensitivity was 0.67 (95% CI 0.66-0.67; P<.001; I²=97.1%), specificity was 0.68 (95% CI 0.67-0.68; P<.001; I²=98.5%), the diagnostic odds ratio was 6.26 (95% CI 4.93-7.94; P<.001; I²=95.3%), the positive likelihood ratio was 2.80 (95% CI 2.46-3.19; P<.001; I²=97.3%), and the negative likelihood ratio was 0.51 (95% CI 0.46-0.57; P<.001; I²=93.6%). This study evaluates prediction models constructed using various ML algorithms, with results showing that ML demonstrates high performance in ARDS prediction. However, many of the existing models still have limitations. During model development, it is essential to focus on model quality, including reducing bias risk, designing appropriate sample sizes, conducting external validation, and ensuring model interpretability. Additionally, challenges such as physician trust and the need for prospective validation must also be addressed. Future research should standardize model development, optimize model performance, and explore how to better integrate predictive models into clinical practice to improve ARDS diagnosis and risk stratification. PROSPERO CRD42024529403; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024529403.

Leukoaraiosis severity and outcomes of endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

Endovascular thrombectomy (EVT) is the standard of care for eligible patients with large vessel occlusion (LVO). Yet, little is known regarding the impact of leukoaraiosis (LA) on outcomes following EVT for LVO. We conducted a systematic review and meta-analysis to investigate the impact of LA on outcomes following EVT. A literature search was performed in PubMed, Embase, Scopus, and Web of Science, from inception until January 7, 2024. Patients were categorized into two groups based on the level of LA: one with absent to mild LA (AMLA) and the other with moderate to severe LA (MSLA). The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0-2. Secondary outcomes included symptomatic intracranial hemorrhage (sICH), thrombolysis in cerebral infarction (TICI) score 2b-3, and mortality. Using R software, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). We included 18 studies with 7022 patients. MSLA was associated with lower rates of mRS 0-2 (OR, 0.32 [95% CI: 0.26-0.41]; p < 0.001), similar rates of TICI 2b-3 (OR, 0.91 [95% CI: 0.77-1.07]; p = 0.235) and sICH (OR, 1.18 [95% CI: 0.92-1.51]; p = 0.202), and greater rates of mortality (OR, 2.89 [95% CI: 2.38-3.52]; p < 0.001) compared to AMLA. MSLA is associated with lower rates of mRS 0-2 and worse safety outcomes following EVT for LVO, despite similar rates of TICI 2b-3. Future prospective studies should further study MSLA as a prognosticator following EVT. Question Does the severity of LA impact functional and safety outcomes following EVT for acute ischemic stroke due to LVO? Findings Moderate-to-severe LA was associated with lower rates of good functional outcome and higher mortality following EVT, despite similar rates of successful reperfusion and sICH. Clinical relevance LA severity is an independent prognostic factor in EVT outcomes. Identifying patients with moderate-to-severe LA can aid in risk stratification and post-procedural management, optimizing individualized stroke treatment and follow-up strategies.

Association of Body Mass Index in Late Life, and Change from Midlife to Late Life, With Incident Dementia in the ARIC Study Participants.

Midlife obesity is a risk factor of dementia, but late-life obesity has been associated with lower dementia risk. We investigated this paradox by exploring the relationship between late-life body mass index (BMI) category and dementia, with and without considering midlife to late-life BMI change. This observational cohort study included participants of the community-based Atherosclerosis Risk in Communities (ARIC) study who were dementia-free at visit 5 (2011-2013). Dementia was ascertained by expert-adjudicated, algorithmic classification from an in-person neuropsychological battery, as well as telephone interviews and International Classification of Diseases codes from medical records. We first assessed the association of incident dementia with visit 5 BMI categories (normal weight, overweight, obese). Next, we used a cross-classification of visit 5 BMI categories with visit 4-visit 5 BMI change (decrease [loss of ≥2 kg/m2], increase [gain of ≥2 kg/m2], or stable [loss or gain of <2 kg/m2]) occurring during the 15 years before baseline. Cox regression was used. A total of 5,129 participants were included in the study (59% female; 22% identified as Black; mean (standard deviation) age at visit 5 of 75 (5) years). Over 8 years of follow-up, 20% of the sample developed dementia (n = 1,026). After covariate adjustment, participants with high late-life BMI had a lower risk of dementia; the hazard ratio (95% CI) was 0.86 (0.73-1.00) for overweight and 0.81 (0.68-0.96) for obesity. In stratified models, elevated dementia risk was observed only for participants of each late-life BMI category whose BMI had decreased from midlife to late life. Compared with normal-weight individuals who had maintained BMI from midlife to late life, the hazard ratio (95% CI) for those with BMI loss was 2.08 (1.62-2.67) for normal-weight individuals, 1.62 (1.25-2.10) for those with overweight, and 1.36 (1.00-1.85) for those with obesity. Our results provide insight into the dementia obesity paradox at older ages, tempering a causal interpretation of high late-life BMI as protective against dementia. Instead, they highlight the importance of considering weight loss from midlife to late life in conjunction with late-life BMI in dementia risk stratification.

Arginine methylation modulates tumor fate and prognosis in clear cell renal cell carcinoma

BackgroundArginine methylation, a key post-translational modification, plays a pivotal role in regulating various cellular processes and has been implicated in cancer progression. However, the potential of arginine methylation-related genes as prognostic markers in clear cell renal cell carcinoma (ccRCC) remains underexplored.MethodsWe utilized public transcriptomic datasets from TCGA, E-MTAB-1980 and ICGC, for model construction and validation. Single-cell RNA sequencing datasets were employed to evaluate gene expression patterns at the cellular level. Consensus clustering, KM survival analysis, and GSVA were applied to identify molecular subtypes and related pathways. Univariate and multivariate Cox regression analyses were applied to develop an arginine methylation-related signature (AMS). Immune profiling, mutation landscape, and drug sensitivity prediction were also employed to explore the model’s association with clinical features, immune infiltration, mutation burden, and therapeutic responses.ResultsThe AMS demonstrated robust prognostic performance, with consistent validation across external cohorts. High-risk patients exhibited significantly worse survival, elevated TMB, and an immunosuppressive tumor microenvironment characterized by increased infiltration of regulatory immune cells. Single-cell RNA sequencing revealed key prognostic genes expressed predominantly in cancer and immune cells, supporting their role in tumor progression and immune interactions.ConclusionThe arginine methylation-based prognostic model provides a reliable framework for survival risk stratification in ccRCC and holds promise for guiding personalized therapeutic strategies. Future research should emphasize clinical validation of this model and explore its potential role in optimizing immunotherapy and targeted treatment strategies for ccRCC.

Association of Nonmodifiable Risk Factors With Alzheimer Disease Blood Biomarkers in Community-Dwelling Adults in the ESTHER Study.

Dementia-related blood biomarkers are the future of large-scale dementia risk stratification; however, the extent to which phosphorylated tau (P-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are associated with nonmodifiable risk factors has yet to be confirmed in the community, and the role of menopause has yet to be investigated. Therefore, the aim of this study was to examine the association of age, sex, APOEe4 status, and menopause, with dementia-related blood biomarker levels (P-tau181, NfL, and GFAP) and rate of change over 11 years in longitudinal biomarker measurements in community-dwelling adults. Within this German population-based Epidemiologische Studie zu Chancen der Verhütung, Früherkennung und optimierten Therapie chronischer Erkrankungen in der älteren Bevölkerung cohort study (n = 9,940), a nested case-control study of 1,026 participants (1:1, without dementia during follow-up: incident dementia during follow-up) aged 50-75 years at baseline followed over 17 years was conducted. Blood biomarker measurements (P-tau181, NfL, and GFAP) were completed in blood from baseline, 8-year, and 11-year follow-ups, and cross-sectional and longitudinal regression analyses were used to assess the association with age, sex, APOEe4, and menopause. The mean age of participants was 64 years, and women accounted for slightly over half (54%) of the sample. Age was cross-sectionally and longitudinally significantly associated with all dementia-related biomarkers (p < 0.001). NfL and GFAP levels more strongly correlated (Spearman R = 0.55 and 0.49) with age at baseline than P-tau181 levels (Spearman R = 0.21). Women experienced significantly higher levels and rates of increase in GFAP (p < 0.001) while men experienced higher levels of NfL after adjusting for age and APOEe4 (p < 0.01). APOEe4 status was significantly associated with baseline and longitudinal levels of P-tau181 (baseline β = 0.30, p < 0.05) and GFAP (baseline β = 15.84, p < 0.001). Of interest, premenopausal status was significantly associated with higher GFAP levels after adjusting for age, sex, and APOEe4 (β = 19.09, p < 0.05). This population-based study on dementia biomarkers found that P-tau181 was dependent on age and APOEe4; NfL on age and sex; and GFAP on age, sex, APOEe4, and menopause status. GFAP levels and rate of increase were higher in women, especially in premenopausal participants. Future research should confirm these findings and further explore the role of menopause in dementia pathogenesis among women.

Impedance Cardiography Is a Potent Non-Invasive Method in Cardiac Output Measurement and Pulmonary Arterial Hypertension Risk Assessment.

Impedance cardiography (ICG) offers a potential alternative for hemodynamic assessment in pulmonary arterial hypertension (PAH) as a non-invasive technique. A total of 132 patients who underwent right heart catheterization (RHC) were included. Cardiac output (CO) and stroke volume (SV) measured by thermodilution during RHC (COTD) and ICG (COICG) were compared. The capacity of ICG in PAH risk stratification and clinical deterioration prediction was also analyzed. Ninety-three pre-capillary pulmonary hypertension patients were enrolled, 54 (58.06%) patients belong to Group 1 PAH, and 39 (41.94%) patients were diagnosed with chronic thromboembolic pulmonary hypertension. The mean COTD was 4.93 ± 1.06 L/min, while the COICG was 4.41 ± 1.23 L/min, showing a moderate correlation (r = 0.49, P < .001). In Group 1 PAH patients, the COTD was 5.13 ± 1.10 L/min, and COICG was 4.57 ± 1.22 L/min (r = 0.52, P < .001). Bland-Altman analysis indicated a mean difference of 0.52 L/min and limits of agreement from -1.76 to 2.80 L/min. The mean SVTD was 64.63 ± 17.10 mL, and the SVICG was 60.94 ± 18.03 mL (r = 0.53, P < .001) with a mean difference of 3.69 mL. After a 1-year follow-up, the CIICG and SVIICG showed potential power in predicting clinical deterioration in PAH patients, with area under the curves of 0.76 and 0.81, respectively. Impedance cardiography measured CO and SV presented an acceptable correlation with RHC in PAH patients. Stroke volume index and cardiac index measured by ICG is potent to identify the low-risk status and predict clinical deterioration in PAH patients.

Design optimization and simulated performance evaluation of a self-collimated cardiac SPECT with simultaneous high sensitivity and resolution.

Cardiac single photon emission computed tomography (SPECT) is an important noninvasive molecular imaging technology for the diagnosis and risk stratification of heart diseases. However, since its inception, the clinical impact of cardiac SPECT has been constrained by its reliance on mechanical collimation using a metal apertured-plate structure, which causes an inherent inverse interdependency between the system's resolution and sensitivity. Recently, our group introduced self-collimation (SC) detector architecture in single photon emission imaging: in a structure with multiple layers of sparsely distributed active detector elements, certain detectors also function as collimators for others. We have shown that SPECT with SC detector architecture transcends the performance of its counterpart with conventional mechanical collimation. This study aims to (1) produce the blueprint of a cardiac SC-SPECT system that achieves high sensitivity and resolution simultaneously, and (2) evaluate the system's performance through Monte Carlo simulation studies. Based on our prior SC-SPECT studies and general design considerations for cardiac imaging, we choose a half-hexagon configuration, comprising three identical trapezoid-shaped detector heads, for the detector gantry of the cardiac SC-SPECT. The targeted field of view (FOV) is a spherical volume with a diameter of 190mm. Each detector head includes a tungsten plate on the side facing the FOV, followed by four stacked detector layers with spacing between each layer. With the distance from the fourth detector layer to the center of FOV, as well as the size of individual detector scintillators fixed, we use an established system resolution and variance evaluation scheme to optimize detector configuration parameters, namely, the placement positions of the first three detector layers, the distribution pattern of the apertures and aperture to metal ratio on the tungsten plate. The SC-SPECT with the set of optimized configuration parameters is then evaluated with a set of simulated phantom studies, and the results are compared against that of a conventional dual-head SPECT system. The phantoms include a hot-rod phantom, a cold-rod phantom, and a XCAT phantom configured for emulating various myocardial ischemia conditions under realistic injection dose and variable acquisition times. A cardiac SC-SPECT design with optimized parameters is obtained. The system achieves an average sensitivity of 0.54% within the FOV, and can clearly resolve hot rods with a diameter of 4mm and cold rods with a diameter of 5mm. In contrast, the conventional SPECT system exhibits an average sensitivity of 0.02% in the FOV, resolves 6 mm diameter hot rods and none of the cold rods (4-9mm) with a body-contour orbit, and resolves 5 mm diameter hot rods and 7 mm diameter cold rods with a 150 mm radius circular orbit. The cardiac SC-SPECT reliably identifies cardiac defects with significantly shorter time than that required by its conventional SPECT reference. The optimized cardiac SC-SPECT shows very promising performance improvement over conventional SPECT.

Development and validation of a pediatric spine surgical invasiveness index.

Development and validation of a pediatric spine surgical invasiveness index.

Clinical Outcome Prediction Model in Tetralogy of Fallot Without Pulmonary Valve Replacement Using Contraction Fraction From the SCOUT-TOF Registry.

Few large scale prediction models of clinical outcomes in repaired tetralogy of Fallot (rTOF) exist. Further, contraction fraction, a novel parameter indexing stroke volume by mass reflecting myocardial efficiency, has not been studied. The goals of this study were to develop and validate an rTOF prediction model of clinical outcome from a single center, the SCOUT-TOF (Single Center Outcomes Using Cardiac Magnetic Resonance in Tetralogy of Fallot) registry, using readily available cardiac magnetic resonance parameters and explore novel metrics. We retrospectively reviewed cardiac magnetic resonance parameters of patients with rTOF undergoing cardiac magnetic resonance from 2005 to 2021. Composite outcome 1 (CO1) included death, transplantation, ventricular tachycardia, and pacemaker placement, and composite outcome 2 (CO2) added cardiovascular hospitalizations. An elastic net was used to identify significant variables to enter a best subsets logistic regression. A group of 761 patients with rTOF were studied with a median follow-up of 4.15 years; 31 and 44 CO1 and CO2 events occurred respectively. Right ventricular (RV) contraction fraction was the most significant predictor for CO1 (area under the curve, 0.72; odds ratio [OR], 0.54; P=0.01) and CO2 (area under the curve, 0.69; OR, 0.60; P=0.01). RV contraction fraction was lower for those met that CO1 and CO2 end points (median 1.84 [1.48-2.39] versus 2.34 [1.72-3.02] and 1.88 [1.51-2.53] versus 2.34 [1.72-3.02] cc×cm2.7/g×m1.4, P<0.01 respectively). Additional significant predictors for CO1 were indexed RV mass/volume and left ventricular ejection fraction whereas for CO2, left ventricular global function index and left ventricular mass were additional predictors. In rTOF, RV contraction fraction, a novel biomarker of ventricular efficiency, may be used to possibly improve risk stratification. In addition, not only RV but left ventricular measures of remodeling should be considered in the follow-up of these patients.

Nonlinear association between AST/ALT ratio and 28-day all-cause mortality following ICU admission in critically ill cirrhotic patients: a retrospective cohort study

BackgroundThe AST/ALT ratio is a biochemical marker associated with poor clinical outcomes in various patients, but its role in severe cirrhosis is unclear. This study investigated the relationship between the AST/ALT ratio and mortality in the intensive care unit (ICU) patients with cirrhosis.MethodsThis retrospective cohort study analyzed 2,090 liver cirrhosis patients from the MIMIC-IV database, focusing on their first ICU admission between 2008 and 2019. The AST/ALT ratio, measured within 24 h of admission, was the exposure variable, and the main outcome was 28-day mortality. A multivariable logistic regression model evaluated the link between the AST/ALT ratio and mortality. Nonlinear relationships were explored using smooth curve fitting and saturation effect analyses. Stratified analyses and interaction tests were also performed based on demographic and clinical characteristics.ResultsThe study involved 2,090 critically ill liver cirrhosis patients, averaging 59.1 years old, with 65% male and a 28-day post-ICU admission mortality rate of 29%. The AST/ALT ratio was linked to mortality risk (adjusted odds ratio (OR) 1.1, 95% confidence interval (CI) 1.0–1.2; p = 0.015), showing a nonlinear pattern with a critical point at 3.6. Below this, each unit increase raised mortality risk by 40% (adjusted OR 1.4, 95% CI 1.2–1.6, p < 0.001), but the effect plateaued beyond this level (adjusted OR 1.0, 95% CI 0.8–1.1, p = 0.600). Subgroup analyses confirmed the consistent association, with interaction P values over 0.05.ConclusionsThe AST/ALT ratio is an independent predictor of 28-day mortality in critically ill cirrhotic patients, with a nonlinear relationship (risk increases up to a ratio of ~ 3.6, then plateaus). This marker could enhance ICU risk stratification and inform clinical decision-making.

Heterogeneity of IKZF1 genomic alterations and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia.

Genomic alterations of IKZF1 are common and associated with adverse clinical features in B-progenitor acute lymphoblastic leukemia (B-ALL). The relationship between the type of IKZF1 alteration, B-ALL genomic subtype and outcome are incompletely understood. B-ALL subtype and genomic alterations were determined using transcriptome and genomic sequencing, and SNP microarray analysis in 688 pediatric patients with B-ALL in the St. Jude Total Therapy XV and 16 studies. IKZF1 alterations were identified in 115 (16.7%) patients, most commonly in BCR::ABL1 (78%) and CRLF2-rearranged, BCR::ABL1-like B-ALL (70%). These alterations were associated with 5-year cumulative incidence of relapse (CIR) of 14.8 ± 3.3% compared to 5.0 ± 0.9% for patients without any IKZF1 alteration (P < 0.0001). In separate multivariable analyses adjusting for genetic subtype groups and other factors, IKZF1 deletions of exons 4-7 (P = 0.0002), genomic IKZF1plus with any IKZF1 deletion (P = 0.006) or with focal IKZF1 deletion (P = 0.0007), and unfavorable genomic subtypes (P < 0.005) were independently adverse prognostic factors. Associations of genomic IKZF1plus and exon 4-7 deletions with adverse outcomes were confirmed in an independent cohort. The type of IKZF1 alteration, together with the subtype, are informative for risk stratification and to predict response in patients with B-ALL.