The presence of a deep lateral femoral notch sign in ACL-injured patients is associated with a 2.7° steeper posterior tibial slope and a 19% higher frequency of lateral meniscal injuries.

PURPOSE: The purpose of this study was to study the relationship between the presence of a deep lateral femoral notch sign (DLFNS) in anterior cruciate ligament (ACL)-injured patients and a higher posterior lateral tibial slope (LPTS), a reduced meniscal bone angle (MBA), a higher LPTS/MBA ratio and a higher incidence of concomitant injuries in primary ACL tears. METHODS: A retrospective case-control study was performed in patients submitted to primary ACL reconstruction with an available preoperative magnetic resonance imaging (MRI) scan. Patients with ACL tears and a femoral impactation with a depth ≥2 mm were assorted to the DLFNS group and patients with ACL tear and without a DLFNS to the control group. LPTS and MBA were measured in MRI. The presence of concomitant injuries (meniscal, posterior cruciate ligament, medial collateral ligament, lateral collateral ligament and bone injuries) was assessed in MRI. Quantitative data are presented in the median ± interquartile range (IQR). RESULTS: There were 206 patients included in the study, with 46 patients assorted to the DLFNS group and 160 patients to the control group. In the DLFNS group, the median LPTS was 6.7° (IQR: 4.0-8.2) versus 4.0° in the control group (IQR: 2.2-6.5) (p = 0.003). The LPTS/MBA ratio was significantly higher in the DLFNS group, with a median of 0.32 (IQR: 0.19-0.44), in comparison to the control group, with a median of 0.19 (IQR: 0.11-0.31) (p < 0.001). The multivariable logistic regression analysis showed that the LPTS is an independent risk factor to having a DLFNS (odds ratio [OR] = 1.161; 95% confidence interval [CI]: 1.042-1.293, p = 0.007). There was a higher incidence of concomitant lateral meniscal injuries in the DLFNS group (67% vs. 48%, p = 0.017). CONCLUSIONS: In patients with ACL tears, the presence of a DLFNS is associated with a steeper lateral posterior tibial slope, as well as a higher incidence of concomitant lateral meniscal injuries. LEVEL OF EVIDENCE: Level III.

Prognostic impact of shock in patients with type A acute aortic syndrome. Results of a nationwide multicenter study.

OBJECTIVE: To evaluate the clinical characteristics, imaging findings, treatment and prognosis of patients with type A acute aortic syndrome (AAS-A) presenting with shock. To assess the impact of surgery in this patient population. METHODS: The study included 521 patients with A-AAS enrolled in the Spanish Registry of Acute Aortic Syndrome (RESA-III) from January-2018 to December-2019. The RESA-III is a prospective, multicenter registry that contains AAS data from 30 tertiary-care hospitals. Patients were classified in two groups according to the clinical presentation with or without shock. Shock was defined as persistent systolic blood pressure <80mmHg despite adequate volume resuscitation. RESULTS: 97 (18.6%) patients with A-AAS presented with shock. Clinical presentation with syncope was much more common in the Shock-group (45.4% vs 10.1%, p=0.001). Patients in the Shock-group had more complications at diagnosis and before surgery: cardiac tamponade (36.2% vs 9%, p<0.001), acute renal failure (28.9% vs 18.2%, p=0.018) and need for orotracheal intubation (40% vs 9.1%, p<0.001). There were no significant differences in aortic regurgitation (51.6% vs 46.7%, p=0.396) between groups. In-hospital mortality was higher among patients with shock (48.5% vs 27.4%, p<0.001). Surgery was associated with a significant mortality reduction both in patients with and without shock. Surgery had an independent protective effect on mortality (OR 0.03, 95% CI (0.00-0.32)). CONCLUSIONS: Patients with AAS-A admitted with shock have a heavily increased risk of mortality. Syncope and pericardial effusion at diagnosis are strongly associated with shock. Surgery was independently associated with a mortality reduction in patients with AAS-A and shock.

Comprehensive characterization of protein modifications using mass spectrometry and dry blood spots.

PURPOSE: The main objective of this study is to characterize and analyze modified peptides in DBS samples. This includes deciphering their specific PTMs and understanding their potential impact on the population or disease cohort under study. EXPERIMENTAL DESIGN: Using mass spectrometry-based proteomic approaches, we performed a comprehensive analysis of DBS samples. Our focus was on the identification and quantification of modified peptides. We also took advantage of recent advances in DBS mass spectrometry to ensure accurate detection and quantification. RESULTS: A comprehensive analysis identified 972 modified peptides in DBS samples. Of these, a subset of 211 peptides was consistently present in all samples, highlighting their potential biological importance and relevance. This indicates a diverse spectrum of PTMs in the proteome of DBS samples. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of mass spectrometry and proteomics has revealed a broad spectrum of modified peptides in DBS samples and highlighted their importance in biological processes and disease progression. Accurate detection of these PTMs may be critical for risk stratification and disease management. This study improves the understanding of molecular mechanisms underlying biological processes and disease development, providing important insights for clinical applications.

Cardiovascular risk factors during pregnancy impact the postpartum cardiac and vascular reverse remodeling.

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.

Postbariatric Abdominoplasty: A Comparative Study on Scarpa Fascia Preservation Versus Classical Technique.

BACKGROUND: Abdominoplasties performed with Scarpa Fascia preservation, improve recovery and reduce complications, particularly seroma. Bariatric patients who experience massive weight loss frequently seek body contouring procedures and represent a high-risk group. This study aimed to evaluate the effects of abdominoplasty with Scarpa Fascia preservation versus the classical technique in a bariatric population. METHODS: A retrospective observational cohort study was performed between March 2015 and March 2021 in 65 postbariatric patients who underwent a classic full abdominoplasty (group A, N = 25) or a similar procedure except for the preservation of Scarpa fascia (group B, N = 40). Total and daily drain output, time until drain removal, long drainers (≥ 6 days), length of hospital stay, emergency department visit, readmission to the hospital, reoperation, local and systemic complications were the outcomes evaluated. RESULTS: Group B had a 3-day reduction in time until drain removal (p < 0.001), a 62.6% reduction of total drain output (p < 0.001) and a 3-day reduction in the length of the hospital stay (p < 0.001). Long drainers (≥ 6 days) were highly reduced (from 56.0% in group A to 7.5% in group B) (p < 0.001). There was a lower incidence of liquid collections in group B, with a 66.7% reduction in seroma incidence. CONCLUSIONS: Abdominoplasty with Scarpa Fascia preservation improves recovery by reducing drain output, allowing earlier drain removal and reducing long periods with suction drains. It also reduces hospital stay and seroma incidence. This technique modifies the high-risk postbariatric patient in such a major way that he behaves like a nonbariatric. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Diagnostic and monitoring applications using near infrared (NIR) spectroscopy in cancer and other diseases.

Early cancer diagnosis plays a critical role in improving treatment outcomes and increasing survival rates for certain cancers. NIR spectroscopy offers a rapid and cost-effective approach to evaluate the optical properties of tissues at the microvessel level and provides valuable molecular insights. The integration of NIR spectroscopy with advanced data-driven algorithms in portable instruments has made it a cutting-edge technology for medical applications. NIR spectroscopy is a simple, non-invasive and affordable analytical tool that complements expensive imaging modalities such as functional magnetic resonance imaging, positron emission tomography and computed tomography. By examining tissue absorption, scattering, and concentrations of oxygen, water, and lipids, NIR spectroscopy can reveal inherent differences between tumor and normal tissue, often revealing specific patterns that help stratify disease. In addition, the ability of NIR spectroscopy to assess tumor blood flow, oxygenation, and oxygen metabolism provides a key paradigm for its application in cancer diagnosis. This review evaluates the effectiveness of NIR spectroscopy in the detection and characterization of disease, particularly in cancer, with or without the incorporation of chemometrics and machine learning algorithms. The report highlights the potential of NIR spectroscopy technology to significantly improve discrimination between benign and malignant tumors and accurately predict treatment outcomes. In addition, as more medical applications are studied in large patient cohorts, consistent advances in clinical implementation can be expected, making NIR spectroscopy a valuable adjunct technology for cancer therapy management. Ultimately, the integration of NIR spectroscopy into cancer diagnostics promises to improve prognosis by providing critical new insights into cancer patterns and physiology.

Quality Indicators Compliance and Survival Outcomes in Breast Cancer according to Age in a Certified Center.

Age as a breast cancer (BC) prognostic factor remains debatable. Several studies have investigated clinicopathological features at different ages, but few make an age group direct comparison. The European Society of Breast Cancer Specialists quality indicators (EUSOMA-QIs) allow a standardized quality assurance of BC diagnosis, treatment, and follow-up. Our objective was to compare clinicopathological features, compliance to EUSOMA-QIs and BC outcomes in three age groups (≤45 years, 46-69 years, and ≥70 years). Data from 1580 patients with staged 0-IV BC from 2015 to 2019 were analyzed. The minimum standard and desirable target on 19 mandatory and 7 recommended QIs were studied. The 5-year relapse rate, overall survival (OS), and BC-specific survival (BCSS) were also evaluated. No meaningful differences in TNM staging and molecular subtyping classification between age groups were found. On the contrary, disparities in QIs compliance were observed: 73.1% in ≤45 years and 46-69 years women vs. 54% in older patients. No differences in loco-regional or distant progression were observed between age groups. Nevertheless, lower OS was found in older patients due to concurrent non-oncological causes. After survival curves adjustment, we underscored evidence of undertreatment impacting BCSS in ≥70 years women. Despite a unique exception-more invasive G3 tumors in younger patients-no age-specific differences in BC biology impacting outcome were found. Although increased noncompliance in older women, no outcome correlation was observed with QIs noncompliance in any age group. Clinicopathological features and differences in multimodal treatment (not the chronological age) are predictors of lower BCSS.

Meniscal Bone Angle Is a Strong Predictor of Anterior Cruciate Ligament Injury.

Purpose: To evaluate the influence of lateral posterior tibial slope (LPTS) and meniscal bone angle (MBA) on primary anterior cruciate ligament (ACL) tear risk in an adult population through the LPTS-MBA ratio. Methods: A retrospective case-control study was performed with patients from a tertiary hospital who underwent primary ACL surgery and had preoperative magnetic resonance imaging (MRI). These subjects were matched by age and sex in a 1:1 ratio to patients who had an MRI without ACL tear. LPTS and MBA were measured on MRI scan. Quantitative data are presented in the median ± interquartile range (IQR). Identification of independent risk factors for primary ACL tear was performed using multivariable logistic regression. Receiver operating characteristics curves detected any variable with strong discriminative capacity. Results: In total, 95 patients with primary ACL tear confirmed on MRI were matched with 95 controls (N = 190). Nearly 80% were male subjects, with a median age of 26 years. In the ACL tear group, the median value of LPTS-MBA ratio was 0.20 (IQR 0.11-0.37) versus 0.12 (IQR 0.08-0.19) in the control group (P = .001). LPTS had a median value of 4.20° in the ACL tear group (IQR 2.05-7.35°) and 2.90° in the control group (IQR, 2.05-5.00°) (P = .026), whereas MBA was 19° (IQR, 16-24°) versus 26° (IQR, 24-30°) (P = .001), respectively. Logistic regression showed that LPTS (odds ratio 1.20, 95% confidence interval 1.03-1.42, P = .021) and MBA (odds ratio 0.78, 95% confidence interval 0.71-0.85, P = .001) were independent predictors. The area under the curve (AUC) of LPTS-MBA ratio was 0.69, greater than that of LPTS alone (AUC = 0.61) but lower than that for MBA (AUC = 0.82). Conclusions: In this study, a reduced MBA was the strongest predictive variable associated with a primary ACL tear. A threshold of 22.35° of MBA was associated with an increased risk of ACL tear, with a sensitivity of 70% and specificity of 84%. A cut-off of 0.22 of LPTS-MBA was associated with an increased risk of ACL tear, with a sensitivity of 55% and specificity of 87%. Level of Evidence: Level III, case-control study.

The Use of Radiomic Analysis in Cardiovascular Diseases.

A The recent years of the cardiovascular medicine saw a rapid development of advanced imaging modalities. The new era of personalized medicine takes advantage of what can be interpreted from medical images, searching for underlying connections between image phenotyping and biological characteristics to support precise clinical decisions. The application of radiomics in cardiovascular imaging has lagged behind other fields, such as oncology. While the current interpretation of cardiac and vascular images mainly depends on subjective and qualitative analysis, radiomics uses advanced image analysis to extract numerous quantitative features from digital images that are unrecognizable to the naked eye. The goal of this narrative review is to highlight the main findings of the recent use of radiomic analysis in the cardiovascular field. English-language articles published in the database PubMed were used for this review. The keywords used in the search included radiomics, cardiovascular or cardiac or aortic. Radiomics is expected to contribute to a more precise phenotyping of the cardiovascular disease, which can improve diagnostic, prognostic, and therapeutic decision making in the near future.

Aortic Valve Surgery in Patients with Infective Endocarditis: Mid-Term Follow-up of Patients Treated With the ST. Jude Medical Trifecta Valve.

BACKGROUND: It is particularly difficult to choose the appropriate prosthesis to treat infective endocarditis. OBJECTIVES: To investigate the outcomes after aortic valve replacement with a stented bioprosthesis (Trifecta) in patients with active or previous infective endocarditis. METHODS: We performed a single-centre, retrospective study including consecutive patients with infective endocarditis who underwent aortic valve replacement between July 2011 and June 2019. Survival and reintervention were assessed as of December 2021. Hospital mortality was defined as death in-hospital or within 30-days of surgery. Kaplan-Meier method was used for time-to-event outcome assessment (all-cause mortality and reoperation). Data are median (minimum and maximum) or absolute (relative) frequencies. RESULTS: We included 51 patients, median age of 69 (40 to 87) years, 78% male. The median follow-up time was 5.4 years and the maximum was 10 years. Most patients (71%) had native valve infective endocarditis and 16% had previous endocarditis. Surgery was urgent in 82%. Hospital mortality occurred in 10 patients (20%). After excluding these patients, 1-, 3-, 6-, and 9-years cumulative survival rates were 93%, 78%, 72%, and 72%, respectively. There were five bioprosthesis-related reoperations: 4 due to endocarditis at 1-year, 3-years, and 5-years on follow-up (n=1, 1 and 2, respectively) and 1 due to non-structural deterioration, 6-years after surgery. CONCLUSIONS: Despite the small sample size, this report supports a satisfactory performance profile of the Trifecta bioprosthesis in the treatment of infective endocarditis.

Interleukin-6, infection and cardiovascular outcomes in acute heart failure: Findings from the EDIFICA registry.

AIMS: Interleukin-6 (IL-6) is upregulated in response to infectious and inflammatory triggers and independently predicts all-cause mortality in acute heart failure (AHF). However, the association of IL-6 with cardiovascular outcomes and its interplay with C-reactive protein and infection, a major precipitating factor in AHF, remains poorly understood. METHODS AND RESULTS: The association between IL-6 and clinical outcomes (180 days) in AHF was evaluated using a cohort of 164 patients from the EDIFICA registry. Median IL-6 levels at admission were 17.4 pg/mL. Patients in the higher admission IL-6 tertile presented with lower blood pressure and more congestion, were diagnosed more frequently with infection, and had a longer hospital stay. Higher IL-6 levels were associated with increased risk of HF rehospitalization (hazard ratio per log2 3.69, 95% confidence interval (CI) 1.26-10.8, p =.017) and the composite of HF rehospitalization or cardiovascular death (hazard ratio per log2 3.50; 95% CI 1.28-9.57; p =.014), independently of major AHF prognosticators, including B-type natriuretic peptide and renal function. However, no independent associations were found for all-cause rehospitalization or mortality. Despite a moderate correlation of IL-6 with C-reactive protein (CRP) levels (R = .51), the latter were not associated with clinical outcomes in this population. CONCLUSIONS: IL-6 levels associate with higher rate of cardiovascular events in AHF, independently of classical prognosticators and evidence of infection, outperforming CRP as an inflammatory outcome biomarker.

Metabolic profiling of induced acute pancreatitis and pancreatic cancer progression in a mutant Kras mouse model.

Untargeted Nuclear Magnetic Resonance (NMR) metabolomics of polar extracts from the pancreata of a caerulin-induced mouse model of pancreatitis (Pt) and of a transgenic mouse model of pancreatic cancer (PCa) were used to find metabolic markers of Pt and to characterize the metabolic changes accompanying PCa progression. Using multivariate analysis a 10-metabolite metabolic signature specific to Pt tissue was found to distinguish the benign condition from both normal tissue and precancerous tissue (low grade pancreatic intraepithelial neoplasia, PanIN, lesions). The mice pancreata showed significant changes in the progression from normal tissue, through low-grade and high-grade PanIN lesions to pancreatic ductal adenocarcinoma (PDA). These included increased lactate production, amino acid changes consistent with enhanced anaplerosis, decreased concentrations of intermediates in membrane biosynthesis (phosphocholine and phosphoethanolamine) and decreased glycosylated uridine phosphates, reflecting activation of the hexosamine biosynthesis pathway and protein glycosylation.

Tracking Prostate Carcinogenesis over Time through Urine Proteome Profiling in an Animal Model: An Exploratory Approach.

Prostate cancer (PCa) is one of the most lethal diseases in men, which justifies the search for new diagnostic tools. The aim of the present study was to gain new insights into the progression of prostate carcinogenesis by analyzing the urine proteome. To this end, urine from healthy animals and animals with prostate adenocarcinoma was analyzed at two time points: 27 and 54 weeks. After 54 weeks, the incidence of pre-neoplastic and neoplastic lesions in the PCa animals was 100%. GeLC-MS/MS and subsequent bioinformatics analyses revealed several proteins involved in prostate carcinogenesis. Increased levels of retinol-binding protein 4 and decreased levels of cadherin-2 appear to be characteristic of early stages of the disease, whereas increased levels of enolase-1 and T-kininogen 2 and decreased levels of isocitrate dehydrogenase 2 describe more advanced stages. With increasing age, urinary levels of clusterin and corticosteroid-binding globulin increased and neprilysin levels decreased, all of which appear to play a role in prostate hyperplasia or carcinogenesis. The present exploratory analysis can be considered as a starting point for studies targeting specific human urine proteins for early detection of age-related maladaptive changes in the prostate that may lead to cancer.

Decoding the radiomic and proteomic phenotype of epicardial adipose tissue associated with adverse left atrial remodelling and post-operative atrial fibrillation in aortic stenosis.

AIMS: Epicardial adipose tissue (EAT) volume and attenuation on computed tomography (CT) have been associated with atrial fibrillation. Beyond these conventional CT measures, radiomics allows extraction of high-dimensional data and deep quantitative adipose tissue phenotyping, which may capture its underlying biology. We aimed to explore the EAT proteomic and CT-radiomic signatures associated with impaired left atrial (LA) remodelling and post-operative atrial fibrillation (POAF). METHODS AND RESULTS: We prospectively included 132 patients with severe aortic stenosis with no prior atrial fibrillation referred for aortic valve replacement. Pre-operative non-contrast CT images were obtained for extraction of EAT volume and other radiomic features describing EAT texture. The LA function was assessed by 2D-speckle-tracking echocardiography peak atrial longitudinal strain and peak atrial contraction strain. The EAT biopsies were performed during surgery for proteomic analysis by sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS). The POAF incidence was monitored from surgery until discharge. Impaired LA function and incident POAF were associated with EAT up-regulation of inflammatory and thrombotic proteins, and down-regulation of cardioprotective proteins with anti-inflammatory and anti-lipotoxic properties. The EAT volume was independently associated with LA enlargement, impaired function, and POAF risk. On CT images, EAT texture of patients with POAF was heterogeneous and exhibited higher maximum grey-level values than sinus rhythm patients, which correlated with up-regulation of inflammatory and down-regulation of lipid droplet-formation EAT proteins. The CT radiomics of EAT provided an area under the curve of 0.80 (95% confidence interval: 0.68-0.92) for discrimination between patients with POAF and sinus rhythm. CONCLUSION: Pre-operative CT-radiomic profile of EAT detected adverse EAT proteomics and identified patients at risk of developing POAF.

Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study.

To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2*Q1062H and VASN*R161Q and an adverse role of AMBP*A286G and CD55*S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer.

Sex differences in circulating proteins of patients with rheumatoid arthritis: A cohort study.

OBJECTIVES: Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in rheumatoid arthritis (RA). Studies focusing on sex differences in circulating proteins in RA patients are scarce. Our objective was to investigate the sex differences in circulating proteins of RA patients. METHODS: Cohort study enrolling 399 RA patients. Ninety-four circulating protein-biomarkers (92CVDIIOlink®  + troponin-T + C-reactive protein) were measured. Clinical, demographic, and echocardiographic characteristics were compared between men and women. Sex differences in biomarker expression were assessed using regression modeling. RESULTS: In all, 306 (76.7%) patients were women. Compared with men, women had less visceral fat, smoked less, had diabetes and chronic obstructive pulmonary disease less frequently, and expressed more fatigue, anxiety, and depression. The association with cardiovascular outcomes did not differ between sexes. After adjusting for potential confounders, women expressed higher levels of circulating proteins related to adipokine signaling and vascular function (eg, leptin and vascular endothelial growth factor), whereas men expressed higher levels of circulating proteins related to extracellular matrix organization and inflammation (eg, matrix metalloproteinase-2 and C-reactive protein). These results were not found in patients without RA. CONCLUSION: Sex differences in circulating proteins reflect distinct pathways implicated in the pathogenesis of RA, including inflammation, adiposity, angiogenesis, and extracellular matrix organization. These findings may help further investigations into factors underlying sex-based differences and allow future studies focused on sex-specific personalized treatment approaches in RA. CLINICALTRIALS: gov ID: NCT03960515.

Multiple versus single arterial grafting in the elderly: a meta-analysis of randomized controlled trials and propensity score studies.

INTRODUCTION: The benefit of adding a second arterial conduit is still controversial, mainly in specific subgroups. We conducted a meta-analysis of randomized controlled trials (RCTs) and propensity score (PS) studies comparing survival and early results in elderly patients who underwent coronary artery bypass grafting (CABG) with multiple (MAG) versus single arterial grafting (SAG). EVIDENCE ACQUISITION: MEDLINE, Web of Science and Cochrane Library were used to find relevant literature (1960-April 2020). Survival at a ≥1-year follow-up and early outcomes were evaluated. Outcomes were collected from matched samples or PS adjusted analysis: hazard ratio (HR) along with their variance, frequencies or odds ratios. Random effect models were used to compute combined statistical measures and 95% confidence intervals (CI) through generic inverse variance method (time-to-event) or Mantel-Haenszel method (binary events). EVIDENCE SYNTHESIS: Eleven PS cohorts and 1 RCT comprising >18,800 patients older than 70 (>6200 MAG and >12,500 SAG) were included in this meta-analysis. MAG was associated with lower long-term mortality (pooled HR: 0.81, 95% CI: 0.72-0.91, P<0.01, I2=64%) in the absence of higher risk of early mortality (pooled OR: 0.74, 95% CI: 0.44 to 1.25, P=0.27, I2=0%). In a meta-regression, MAG survival advantage was more pronounced in studies with a higher MAG usage rate (ß=-0.0052, P=0.021). CONCLUSIONS: Current evidence suggests that advanced age should not limit MAG's use considering its benefits in long-term survival. Of note, an individualized patient selection for this approach is warranted.

A systematic review and meta-analysis of randomized controlled studies comparing off-pump versus on-pump coronary artery bypass grafting in the elderly.

INTRODUCTION: Comparison of short and mid-term outcomes between off-pump CABG (OPCAB) and on-pump CABG (ONCAB) in patients older than 65 throughout a meta-analysis of randomized clinical trials (RCTs). EVIDENCE ACQUISITION: A literature search was conducted using 3 databases. RCTs reporting mortality outcomes of OPCAB versus ONCAB among the elderly were included. Data on myocardial infarction, stroke, re-revascularization, renal failure and composite endpoints after CABG were also collected. Random effects models were used to compute statistical combined measures and 95% confidence intervals (CI). EVIDENCE SYNTHESIS: Five RCTs encompassing 6221 patients were included (3105 OPCAB and 3116 ONCAB). There were no significant differences on mid-term mortality (pooled HR: 1.02, 95%CI: 0.89-1.17, P=0.80) and composite endpoint incidence (pooled HR: 0.98, 95%CI: 0.88-1.09, P=0.72) between OPCAB and ONCAB. At 30-day, there were no differences in mortality, myocardial infarction, stroke and renal complications. The need for early re-revascularization was significantly higher in OPCAB (pooled OR: 3.22, 95%CI: 1.28-8.09, P=0.01), with a higher percentage of incomplete revascularization being reported for OPCAB in trials included in this pooled result (34% in OPCAB vs. 29% in ONCAB, P<0.01). CONCLUSIONS: Data from RCTs in elderly patients showed that OPCAB and ONCAB provide similar mid-term results. OPCAB was associated with a higher risk of early re-revascularization. As CABG on the elderly is still insufficiently explored, further RCTs, specifically designed targeting this population, are needed to establish a better CABG strategy for these patients.

Frailty-Independent Undertreatment Negative Impact on Survival in Older Patients With Breast Cancer.

PURPOSE: The management of older adults with breast cancer (BC) remains controversial. The challenging assessment of aging idiosyncrasies and the scarce evidence of therapeutic guidelines can lead to undertreatment. Our goal was to measure undertreatment and assess its impact on survival. METHODS: Consecutive patients with BC aged 70 years or older were prospectively enrolled in 2014. Three frailty screening tools (G8, fTRST, and GFI) and two functional status scales (Karnofsky performance score and Eastern Cooperative Oncology Group Performance Status) were applied. Disease characteristics, treatment options, and causes of mortality were recorded during a 5-year follow-up. In addition, we defined undertreatment and correlated its survival impact with frailty. RESULTS: A total of 92 patients were included in the study. The median age was 77 (range 70-94) years. The prevalence of frailty was discordant (G8, 41.9%; fTRST, 74.2%; GFI, 32.3%). Only 47.8% of the patients had a local disease, probably due to a late diagnosis (73.9% based on self-examination). Thirty-three patients (35.6%) died, of which 15 were from BC. We found a considerably high proportion (53.3%) of undertreatment, which had a frailty-independent negative impact on the 5-year survival (hazard ratio [HR], 5.1; 95% confidence interval [CI], 2.1-12.5). Additionally, omission of surgery had a frailty-independent negative impact on overall survival (HR, 3.9; 95% CI, 1.9-7.9). CONCLUSION: BC treatment in older adults should be individualized. More importantly, assessing frailty (not to treat) is essential to be aware of the risk-benefit profile and the patient's well-informed willingness to be treated. Undertreatment in daily practice is frequent and might have a negative impact on survival, as we report.

Mining the Biomarker Potential of the Urine Peptidome: From Amino Acids Properties to Proteases.

Native biofluid peptides offer important information about diseases, holding promise as biomarkers. Particularly, the non-invasive nature of urine sampling, and its high peptide concentration, make urine peptidomics a useful strategy to study the pathogenesis of renal conditions. Moreover, the high number of detectable peptides as well as their specificity set the ground for the expansion of urine peptidomics to the identification of surrogate biomarkers for extra-renal diseases. Peptidomics further allows the prediction of proteases (degradomics), frequently dysregulated in disease, providing a complimentary source of information on disease pathogenesis and biomarkers. Then, what does urine peptidomics tell us so far? In this paper, we appraise the value of urine peptidomics in biomarker research through a comprehensive analysis of all datasets available to date. We have mined > 50 papers, addressing > 30 different conditions, comprising > 4700 unique peptides. Bioinformatic tools were used to reanalyze peptide profiles aiming at identifying disease fingerprints, to uncover hidden disease-specific peptides physicochemical properties and to predict the most active proteases associated with their generation. The molecular patterns found in this study may be further validated in the future as disease biomarker not only for kidney diseases but also for extra-renal conditions, as a step forward towards the implementation of a paradigm of predictive, preventive and personalized (3P) medicine.