Purpose: Keratoconus is traditionally classified as a noninflammatory corneal ectasia, despite growing evidence suggesting an underlying inflammatory component. This study evaluates whether patients with stable keratoconus exhibit persistent inflammatory activity in tear fluid compared to healthy controls. Methods: Cross-sectional case-control study. Keratoconus progression was evaluated using tomographic and clinical criteria. Tear fluid samples were collected under standardized conditions and concentrations of nine cytokines (IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, and TNF-α) were quantified using a multiplex assay. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curves were performed to evaluate cytokine expression and network behavior. Results: A total of 23 stable keratoconus patients and 25 age-matched healthy controls were included. The stable keratoconus group exhibited significantly elevated levels of tear fluid inflammatory cytokines compared to controls (all P < 0.05, except IL-2). Spearman correlation heatmaps revealed a coordinated cytokine network in the keratoconus group, suggesting persistent immunological activation despite clinical quiescence. No significant correlations were observed between cytokine levels and keratoconus staging indices. ROC analysis indicated moderate discriminatory performance of IL-6 (area under the curve = 0.68). Conclusions: Even clinically stable keratoconus is associated with a distinct proinflammatory tear fluid cytokine profile, challenging the traditional paradigm of keratoconus as a noninflammatory disease. These findings highlight the potential utility of tear fluid-based inflammatory biomarkers in keratoconus and suggest inflammation may persist independently of clinical progression. Translational relevance: This study highlights the potential role of tear-based inflammatory biomarkers for monitoring disease activity, understanding keratoconus pathophysiology and guiding adjunctive anti-inflammatory therapies in keratoconus beyond structural stabilization.

Background: There is increasing evidence for the role of inflammation in clinical outcome after subarachnoid hemorrhage (SAH). Specifically, the TNF-alfa(α) pathway seems to be relevant after SAH. Although the TNF-α main receptor, TNF-R1 is associated with aneurysm growth and rupture, its relation to prognosis is unknown. We sought to compare TNF-R1 levels in peripheral venous blood and arterial blood closer to the ruptured aneurysm to study the association of TNF-R1 blood levels with poor prognosis (modified Rankin Scale > 2 at discharge, 3 and 6 months) and complications (hydrocephalus or delayed cerebral ischemia/DCI) following SAH. Methods: We included consecutive SAH patients admitted in the first 72 h of symptoms. Blood samples were simultaneously collected from a peripheral vein and from the main parent artery of the aneurysm. Levels of TNF-R1 were measured using enzyme-linked immunosorbent assays. Results: We analyzed 58 patients. Arterial and venous levels of TNF-R1 were correlated (R = 0.706, p < 0.001). In multivariate regression analysis, venous TNF-R1 was an independent predictor of poor outcome at 6 months after adjusting by age and sex [odds ratio (OR) 11.63; 95% CI 2.09-64.7, p = 0.005] and after adjusting by Glasgow Coma Scale and Fisher scales (OR 8.74; 95% CI 1.45-52.7, p = 0.018). There was no association of TNF-R1 with DCI. A cut-off for arterial TNF-R1 of 1523.7 pg/mL had 75% sensitivity/66% specificity for the prediction of hydrocephalus. Conclusion: Levels of venous TNF-R1 are associated with poor outcome in SAH. A specific association was found between levels of arterial TNF-R1 and hydrocephalus. These results are consistent with the role of TNF-α pathway in SAH and need to be validated in larger cohorts.

OBJECTIVE: To compare performance of multimarker algorithm, risk profiles and their sequential application in prediction of preeclampsia and determining potential intervention targets. STUDY DESIGN: Maternal characteristics, ultrasound variables and serum biomarkers were collected prospectively at first trimester. Univariate analysis identified preeclampsia associated variables followed by logistic regression analysis to determine the prediction rule. Combined characteristics of the cardiovascular, metabolic and the personal risk factors were compared to the multimarker algorithm and the sequential application of both methods. RESULTS: Out of 2433 women, 108 developed preeclampsia (4.4%). Probability scores considering nulliparity, prior preeclampsia, body mass index, diastolic blood pressure and placental growth factor had an area under the receiver operating characteristic curve 0.784 (95% CI = 0.721-0.847). While the multimarker algorithm had the lowest false negative rate, sequential application of cardiovascular and metabolic risk profiles in screen positives reduced false positives by 26% and identified blood pressure and metabolic risk in 49/54 (91%) women with subsequent preeclampsia as treatable risk factors. CONCLUSION: Sequential application of a multimarker algorithm followed by determination of treatable risk factors in screen positive women is the optimal approach for first trimester preeclampsia prediction and identification of women that may benefit from targeted metabolic or cardiovascular treatment

Objective: Predicting mortality risk following orthopedic surgery is crucial for informed decision-making and patient care. This study aims to develop and validate a machine learning model for predicting one-year mortality risk after orthopedic hospitalization and to create a personalized risk prediction tool for clinical use. Methods: We analyzed data from 3,132 patients who underwent orthopedic procedures at the Central Lisbon University Hospital Center from 2021 to 2023. Using the LightGBM algorithm, we developed a predictive model incorporating various clinical and administrative variables. We employed SHAP (SHapley Additive exPlanations) values for model interpretation and created a personalized risk prediction tool for individual patient assessment. Results: Our model achieved an accuracy of 93% and an area under the ROC curve of 0.93 for predicting one-year mortality. Notably, 'EMERGENCY ADMISSION DATE TIME' emerged as the most influential predictor, followed by age and pre-operative days. The model demonstrated robust performance across different patient subgroups and outperformed traditional statistical methods. The personalized risk prediction tool provides clinicians with real-time, patient-specific risk assessments and insights into contributing factors. Conclusion: Our study presents a highly accurate model for predicting one-year mortality following orthopedic hospitalization. The significance of 'EMERGENCY ADMISSION DATE TIME' as the primary predictor highlights the importance of admission timing in patient outcomes. The accompanying personalized risk prediction tool offers a practical means of implementing this model in clinical settings, potentially improving risk stratification and patient care in orthopedic practice.

Objective: To investigate whether glycated albumin, fructosamine, and hemoglobin A1c (HbA1c) are associated with neonatal complications in newborns of pregnant women with gestational diabetes mellitus (GDM). Methods: Between November 2016 and September 2017, women with a singleton pregnancy and GDM were enrolled in a prospective study in an obstetric Portuguese referral center. Glycemic markers were compared between mothers of newborns with and without complications. Multivariable logistic regression models and corresponding areas under the receiver operating characteristic curve (AUC) were used. Results: A total of 85 women participated in the study. Raised levels of glycated albumin and fructosamine were associated with at least one neonatal complication (OR- [odds ratio] estimate: 1.33, P=0.015; OR: 1.24, P=0.027, respectively) and with respiratory disorders at birth (OR 1.41, P=0.004; OR 1.26, P=0.014, respectively). HbA1c was not associated with these outcomes. All biomarkers were associated with large-for-gestational age (LGA) status (OR 1.61, P<0.001; OR 1.45, P<0.001; OR 3.62, P=0.032 for glycated albumin, fructosamine, and HbA1c, respectively). All had similar AUC for at least one neonatal complication (0.82; 0.81; 0.79, respectively). For newborn respiratory disorders, AUCs were 0.83, 0.81, and 0.76, respectively, and for LGA status were 0.81, 0.79, and 0.71, respectively. Conclusion: Raised values of glycated albumin and fructosamine were associated with particular perinatal complications in newborns of mothers with GDM, better discriminating mothers of newborns with and without complications than HbA1c.

B-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.

Sjögren's Syndrome (SjS) is a chronic systemic immune-mediated inflammatory disease characterized by lymphocytic infiltration and consequent lesion of exocrine glands. SjS diagnosis and classification remains a challenge, especially at SjS onset, when patients may have milder phenotypes of the disease or uncommon presentations. New biomarkers are needed for the classification of SjS, thus, we aimed to evaluate the added-value of lymphocyte subpopulations in discriminating SjS and non-Sjögren Sicca patients. Lymphocyte subsets from 62 SjS and 63 Sicca patients were characterized by flow cytometry. The 2002 AECG and the 2016 ACR/EULAR SjS classification criteria were compared with clinical diagnosis. The added discriminative ability of joining lymphocytic populations to classification criteria was assessed by the area under the Receiver-Operating-Characteristic Curve (AUC). Considering clinical diagnosis as the gold-standard, we obtained an AUC = 0.952 (95% CI: 0.916-0.989) for AECG and an AUC = 0.921 (95% CI: 0.875-0.966) for ACR/EULAR criteria. Adding Tfh and Bm1 subsets to AECG criteria, performance increased, attaining an AUC = 0.985 (95% CI: 0.968-1.000) (p = 0.021). Th1/Breg-like CD24hiCD27+ and switched-memory B-cells maximized the AUC of ACR/EULAR criteria to 0.953 (95% CI: 0.916-0.990) (p = 0.043). Our exploratory study supports the potential use of lymphocyte subpopulations, such as unswitched memory B cells, to improve the performance of classification criteria, since their discriminative ability increases when specific subsets are added to the criteria.

BACKGROUND: This study aimed to determine the relationship between CK19 mRNA copy number in sentinel lymph nodes (SLN) assessed by one-step nucleic acid amplification (OSNA) technique, and non-sentinel lymph nodes (NSLN) metastization in invasive breast cancer. A model using total tumor load (TTL) obtained by OSNA technique was also constructed to evaluate its predictability. METHODS: We conducted an observational retrospective study including 598 patients with clinically T1-T3 and node negative invasive breast cancer. Of the 88 patients with positive SLN, 58 patients fulfill the inclusion criteria. RESULTS: In the analyzed group 25.86% had at least one positive NSLN in axillary lymph node dissection. Univariate analysis showed that tumor size, TTL and number of SLN macrometastases were predictive factors for NSLN metastases. In multivariate analysis just the TTL was predictive for positive NSLN (OR 2.67; 95% CI 1.06-6.70; P = 0.036). The ROC curve for the model using TTL alone was obtained and an AUC of 0.805 (95% CI 0.69-0.92) was achieved. For TTL >1.9 × 105 copies/μL we got 73.3% sensitivity, 74.4% specificity and 88.9% negative predictive value to predict NSLN metastases. CONCLUSION: When using OSNA technique to evaluate SLN, NSLN metastases can be predicted intraoperatively. This prediction tool could help in decision for axillary lymph node dissection.

The Level of Personality Functioning Scale-Self-Report (LPFS-SR) operationalizes Criterion A of the DSM-5 Alternative Model for Personality Disorders. The current study aimed 1) to examine the internal consistency of the Portuguese version of the LPFS-SR in a community sample and a clinical sample, 2) to compare non-clinical participants (N = 282, Mage = 48.01, SD = 10.87) with two samples of clinical participants, one composed of patients with a personality disorder diagnosis (PD sample, n = 40, Mage = 46.18, SD = 13.59) and the other of patients with other psychiatric diagnoses (OD sample, n = 148, Mage = 49.49, SD = 11.88), with respect to LPFS-SR dimensions and total score, 3) to examine the capacity of the LPFS-SR to discriminate between samples through the ROC curve analyses, and 4) to examine the factor structure of the Portuguese version of the LPFS-SR. The Portuguese version of the LPFS-SR revealed adequate internal consistency results, akin to the original data, in the community and clinical samples. The community sample differed significantly from both clinical samples in all the LPFS-SR dimensions and total score. The ROC curve analysis indicated an optimal cut-off for the total score of 272.00, corresponding to a sensitivity of 75% and a specificity of 89%, in the PD vs. community samples. The LPFS-SR total score discriminative capacity between the PD and OD samples was lower, albeit also significant (area-under-the-curve of .63; p = .027; 95% CI: .52-.74). The current study provided evidence of the LPFS-SR's unidimensionality in both community and clinical samples. Although this study has limitations, its findings contribute to a deeper understanding of the LPFS-SR construct, as well as to its cross-cultural validation.

GOALS OF WORK: Recent literature has indicated the need for rapid evaluation of psychosocial issues secondary to cancer. Because of the problems of routine use of psychometric instruments, short instruments such as visual analogue scales or one-item 0-10 scales have been developed as valid assessment alternatives. PATIENTS AND METHODS: A study was conducted to examine the role of two 0-10 scales in measuring emotional stress (distress thermometer, DT) and depressed mood (mood thermometer, MT), respectively, in a multicenter study carried out in southern European countries (Italy, Portugal, Spain, and Switzerland). A convenience sample of 312 cancer outpatients completed the DT and MT and the Hospital Anxiety Depression Scale (HADS). MAIN RESULTS: DT was more significantly associated HADS anxiety than HADS depression while MT was related both to HADS anxiety and depression. The correlation of MT with HADS was higher than DT. A cutoff point >4 on the DT maximized sensitivity (65%) and specificity (79%) for general psychosocial morbidity while a cutoff >5 identified more severe "caseness" (sensitivity=70%; specificity=73%). On the MT, sensitivity and specificity for general psychosocial morbidity were 85% and 72% by using the cutoff score >3. A score >4 on the MT was associated with a sensitivity of 78% and a specificity of 77% in detecting more severe caseness. CONCLUSIONS: Two simple instruments, the DT and the MT, were found to have acceptable levels of sensitivity and specificity in detecting psychosocial morbidity. Compared to the HADS, however, the mood MT performed better than the DT.