Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

There is now evidence that, based on cytokine profiles, bipolar disorder (BD) is accompanied by simultaneous activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS), and that both components may be associated with the staging of illness. Nevertheless, no BD studies have evaluated the IRS/CIRS ratio using CD (cluster of differentiation) molecules expressed by peripheral blood activated T effector (Teff) and T regulatory (Treg) subpopulations. This study examined T cell subsets both before and after ex vivo anti CD3/CD28 stimulation using flow cytometric immunophenotyping in 25 euthymic BD patients and 21 healthy controls as well as human cytomegalovirus (HCMV)-specific IgG antibodies. BD is associated with a significantly lowered frequency of baseline (unstimulated) CD3+CD8+CD71+ and CD4+CD25+FOXP3 and increased CD4+CD25+FOXP3+CD152+ frequencies and with lowered stimulated frequencies of CD3+CD8+CD71+, CD4+CD25+FOXP3+CD152+ and CD4+CD25+FOXP3+GARP cells and, consequently, by an increased stimulated Teff/Treg ratio. Moreover, the number of manic, but not hypomanic or depressive episodes, is significantly and negatively associated with the stimulated proportions of CD3+CD4+CD154+, and CD69+ and CD71+ expression on CD4+ and CD8+ cells, while duration of illness (≥ 10 years) is accompanied by a depleted frequency of stimulated CD152+ Treg, and CD154+ and CD71+ CD4+ T cells. BD and anti-human cytomegalovirus (HCMV) IgG levels significantly interact to decrease the expression of CD4+CD25+FOXP+GARP T phenotypes. In conclusion, BD is characterized by deficits in immune-regulatory functions while the staging of illness is characterized by additional impairments is Teff and Treg activation. HCMV seropositivity may contribute to an immune-risk phenotype associated with BD.

Breast cancer has become the most diagnosed cancer in women globally with 2.3 million new diagnosis each year. Accurate early staging is essential for improving survival rates with metastatic spread from loco regional to distant metastasis decreasing rates by 50%. Current guidelines do not advice the routine use of Positron Emission Tomography (PET)-Computed Tomography (CT) in staging of early breast cancer in the absence of symptoms. However, there is a growing body of evidence to suggest that PET-CT used in this early stage can benefit the patient by improving staging and as a result treatment and outcome as well as psychological burden without increasing costs to the health service. Ongoing research in PET radiomics and artificial intelligence is showing promising future prospects in its use in diagnosis, staging, prognosticatication and assessing response to treatment in breast cancer. Furthermore ongoing research to address current limitations of PET-CT by improving techniques and tracers is encouraging.

(1) Background: Overall survival of the patients with renal cell carcinoma (RCC) depends mostly on extra-renal extension, documented by the invasion of the pelvicalyceal system, or the perinephric/renal sinus fat or the renal vein/its segmental intraparenchymal branches. Staging may be challenging because of the high inter-observer variability. We have introduced a more accurate procedure to detect the extra-renal extension and, to possibly evaluate the impact of such more laborious approach, we have compared the RCC pathological staging obtained following both standard and modified procedures; (2) Methods: We selected 54 consecutive cases of RCC diagnosed 18 months before and 54 consecutive cases diagnosed 18 months after the introduction of the new method of sampling. Clinico-pathological characteristics have been statistically analyzed; (3) Results: Most of the features analyzed were non statistically significative, except the extra-renal invasion. More precisely, the occurrence of retrograde venous invasion was higher in the cases grossly approached with the more accurate method; (4) Conclusions: Extra-renal extension to intraparenchymal renal vein branches may be underestimated, leading to an inappropriate under-staging. Using more accurate staging procedures, to disclose the occurrence of intra-renal veins tumoral thrombosis, helps to better define the pathological stage, allowing patients to benefit of better fitting treatments.

Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guide-lines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ES-GO-ESTRO-ESP recommendations was performed furtherly confirming this statement. Trans-vaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumour delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insuffi-cient sensitivity to detect small-volume metastases, as any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, con-trast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography in combination with CT (PET-CT) are recommended to assess extrapelvic spread. The aim of this paper is to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer.

Renal angiogram is a promising tool for diagnosing renal vasculature and structural alterations in renal diseases. In renal diseases, the vascular changes were observed earlier than the structural and other changes. However, the literature on angiograms in kidney diseases was limited. Six client-owned dogs with chronic kidney diseases with International Renal Interest Society (IRIS) stage II and III were selected for this study. Under general anesthesia, the femoral arterial catheterization was performed. With a Cobra (C2) catheter, Iohexol saline (50:50) was administered to evaluate the vascular changes of Renal failure, using selective and non-selective angiograms. The procedures were completed successfully with minimal complications. Serum biochemistry and urine protein creatinine ratio were estimated sequentially and quality of life was monitored. Due to contrast agent complications, a dog died within 14 days and necropsy was conducted. Though the renal angiogram has complications, it is a reliable tool for the diagnosis of vasculature changes associated with kidney diseases, in veterinary medicine.

Background: Myometrial invasion (MI) is a parameter currently used in transvaginal ultrasound (TVS) in endometrial cancer (EC) to determine local staging, however, without molecular diagnostics, it is insufficient for selection of high-risk cases, i.e., those with a high risk of lymph node metastases (LNM). Methods: One hundred sixteen consecutive EC patients, who had received 2D transvaginal ultrasound examinations in their preoperative workup and final histopathology results as a reference standard, were included in this prospective study. Univariate and multivariate logistic models of analyzed TVS biomarkers (tumor [T] size, T area [AREA], T volume [SPE-VOL], MI, T-free distance to serosa [TFD], endo-myometrial irregularity, [EMIR], cervical stromal involvement, CSI) were evaluated to assess the relative accuracy of the possible LNM predictors. To avoid a potential bias in assuming linear relations between LNM and continuous predictors, spline functions were applied. Calculations were made in R with the use of libraries splines, glmulti, and pROC. Results: LNM was found in 20 out of 116 (17%) patients. In univariate analysis, only uMI, EMIR, uCSI and uTFD were significant predictors of LNM. Accuracy was 0.707 (AUC 0.684, 95% CI 0.568-0.801) for uMI (p<0.01), 0.672 (AUC 0.664, 95% CI 0.547-0.781) for EMIR (p<0.01), 0.776 (AUC 0.647, 95% CI 0.529-0.765) for uCSI (p<0.01), and 0.638 (AUC 0.683, 95% CI 0.563-0.803) for uTFD (p<0.05). The cut-off value for uTFD was 5.2 mm. However, AREA and VOL revealed significant relation by non-linear analysis as well. Among all possible multivariate models, the one comprising interactions of splines of uTFD with uMI and splines of SPE-VOL with uCSI showed most usefulness. Accuracy was 0.802 (AUC 0.791, 95% CI 0.673-0.91) Conclusions: A combination of uTFD for patients with uMI>50%, and SPE-VOL for patients with uCSI, allows for the most accurate prediction of LNM in EC, rather than uMI alone.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

More and more people quantify their sleep using wearables and are getting obsessed in their pursuit of optimal sleep (“orthosomnia”). However, it is criticized that many of these wearables are giving inaccurate feedback and even can lead to negative daytime consequences. Acknowledging these facts, we here aim to extend previous findings [] in a new sample of 136 self-reported poor sleepers by implementing optimization procedures to minimize erroneous classification when ambulatory sensing sleep. Firstly, here, we introduce an advanced interbeat-interval (IBI) quality control using a random forest method to account for wearable recordings in naturalistic and more noisy settings. We further aim to improve sleep classification by opting for a loss function model instead of overall epoch-by-epoch accuracy to avoid model biases towards the majority class (i.e., “light sleep”). Using these implementations, we compare the classification performance between the optimized (loss function model) and the accuracy model. We use signals derived from PSG, one-channel ECG, and two consumer wearables: the ECG breast belt Polar® H10 (H10) and the Polar® Verity Sense (VS), an optical Photoplethysmography (PPG) heart-rate sensor. Results reveal high overall accuracy for the new model for ECG (86.3 %, κ=.79), H10 (84.4%, κ=.76), and VS (84.2%, κ=.75) with intended improvements in deep sleep and wake. In addition, the new optimized model displays moderate to high correlations and agreement with PSG on primary sleep parameters, while measures of reliability, expressed in intra-class correlations, suggest excellent reliability for most sleep parameters. Finally, it is demonstrated that the new model is still classifying sleep accurately in 4-classes in users taking heart-affecting and/or psychoactive medication which can be considered a prerequisite for use also in high age groups and/or with common disorders. Further improving and validating sleep stage classification algorithms with affordable wearables may resolve existing scepticism and open the door for such approaches in clinical practice.

The accuracy of multi-parametric MRI (mpMRI) in pre-operative staging of prostate cancer (PCa) remains controversial. Objective: To evaluate the ability of mpMRI to accurately predict PCa extra-prostatic extension (EPE) on a side-specific basis using a risk-stratified 5-point Likert scale. This study also aimed to assess the influence of mpMRI scan quality on diagnostic accuracy. Patients and Methods: We included 124 men who underwent robot-assisted RP (RARP) as part of the NeuroSAFE PROOF study at our centre. Three radiologists retrospectively reviewed mpMRI blinded to RP pathology and assigned a Likert score (1-5) for EPE on each side of the prostate. Each scan was also ascribed a Prostate Imaging Quality (PI-QUAL) score for assessing the quality of the mpMRI scan, where 1 represents poorest and 5 represents best diagnostic quality. Outcome measurements and statistical analyses: Diagnostic performance is presented for binary classification of EPE including 95% confidence intervals and area under the receiver operating characteristic curve (AUC). Results: A total of 231 lobes from 121 men (mean age 56.9 years) were evaluated. 39 men (32.2%), or 43 lobes (18.6%) had EPE. Likert score ≥3 had sensitivity (SE), specificity (SP), NPV, PPV of 90.4%, 52.3%, 96%, 29.9%, respectively, and AUC was 0.82 (95% CI: 0.77-0.86). AUC was 0.63 (95% CI: 0.37-0.9), 0.77 (0.71-0.84) and 0.92 (0.88-0.96) for biparametric scans, PI-QUAL 1-3 and PI-QUAL 4-5 scans, respectively. Conclusions: MRI can be used effectively by genitourinary radiologists to rule out EPE and help inform surgical planning for men undergoing RARP. EPE prediction was more reliable when the MRI scan was a) multi-parametric and b) of a higher image quality according to the PI-QUAL scoring system.

Objectives: This study aimed to assess the impact of a predictive model for detecting extracapsular extension on pathology (pECE+) on biochemical recurrence-free survival (BCRFS) within 4 years after robotic-assisted radical prostatectomy (RARP). Methods: Retrospective data analysis from a single center between 2015 to 2022. Variables under consideration included prostate-specific antigen (PSA) levels, patient age, prostate volume, MRI semantic features and Gleason score (GS). We also assessed the influence of pECE+ and positive surgical margins on BCRFS. using the Kaplan-Meier survival function and Cox regression model were assessed. Additionally, we analyzed the MRI features on BCR (biochemical recurrence) in low/intermediate risk patients. Results: 177 participants with a follow-up exceeding 6 months post-RARP were included. The 1-year, 2-year, and 4-year risks of BCR after curative prostatectomy were 5%, 13%, and 21%, respectively. The survival analysis showed that adverse MRI features as macroscopic ECE on MRI (mECE+), capsular disruption, high tumor capsular contact length (TCCL), GS≥8, positive surgical margins (PSM), and pECE+ on pathology were risk factors for BCR. In low/intermediate-risk patients (pECE- and GS &lt;(4+4)) the presence of adverse MRI features, has been shown to increase the risk of BCR. Conclusions: The study highlights the importance of incorporating predictive MRI features for detecting extracapsular extension pre-surgery in influencing early outcomes and clinical decision-making; mECE+, TCCL, capsular disruption, and GS≥8 based on pre-surgical biopsy were independent prognostic factors for early BCR. The presence of adverse features on MRI can assist in identifying low/intermediate-risk patients who would benefit from closer monitoring.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.