OBJECTIVES: Pseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites. METHODS: Adult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonization in the perianal area and in the lower respiratory tract was assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonization as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP. RESULTS: A total of 1971 subjects were enrolled. The colonization prevalence with PA in the first 72 hours of ICU admission was 10.4% (179 perianal and 51 respiratory), whereas the acquisition incidence during the ICU stay was 7.0% (158 perianal and 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonized on admission and 9 (20.9%) acquired colonization before PAIP onset. Both perianal (adjusted subdistribution hazard ratio, 4.4; 95% CI, 1.7-11.6) and respiratory colonization (adjusted subdistribution hazard ratio: 4.6, 95% CI, 1.9-11.1) were independently associated with PAIP development. DISCUSSION: PAIP incidence was higher in PA colonized vs. non-colonized patients. Colonization of both the rectum and of the respiratory tract was associated with development of PAIP. The increased risk of PA colonization for subsequent infection provides an opportunity for targeted preventive interventions.
- MeSH
- Adult MeSH
- Incidence MeSH
- Cross Infection epidemiology microbiology MeSH
- Intensive Care Units * statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Carrier State epidemiology microbiology MeSH
- Prevalence MeSH
- Prospective Studies MeSH
- Pseudomonas Infections * epidemiology microbiology MeSH
- Pseudomonas aeruginosa * isolation & purification MeSH
- Aged MeSH
- Pneumonia, Ventilator-Associated epidemiology microbiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Geographicals
- Europe MeSH
INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- Adult MeSH
- Humans MeSH
- Placental Circulation physiology MeSH
- Placenta Growth Factor * blood MeSH
- Area Under Curve MeSH
- Predictive Value of Tests MeSH
- Pre-Eclampsia * blood diagnostic imaging MeSH
- Vascular Endothelial Growth Factor Receptor-1 * blood MeSH
- Rheology * methods statistics & numerical data MeSH
- Reproducibility of Results MeSH
- Blood Flow Velocity physiology MeSH
- Pregnancy MeSH
- Pregnancy Trimester, Third * blood physiology MeSH
- Ultrasonography, Doppler methods statistics & numerical data MeSH
- Ultrasonography, Prenatal * methods statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
BACKGROUND: Many studies have demonstrated the association between low birth weight (LBW) and chronic kidney disease, estimated glomerular filtration rate (eGFR) and kidney volume (KV). However, studies on twins and those investigating numerous perinatal factors beyond LBW, and their associations with various kidney parameters are scarce. METHODS: A two-center cross-sectional study on five-year-old LBW children was conducted between 2021 and 2023. 110 children were enrolled (8 LBW, 58 very LBW (VLBW), 44 extremely LBW (ELBW)); 56 were twins. We examined associations between birth weight (BW), various prenatal, perinatal and postnatal factors, and eGFR, KV, tubular abnormalities and kidney ultrasound abnormalities, both in singletons and twins. RESULTS: In children with ELBW, eGFR correlated with BW (r = 0.55, P = 0.0018), while in those with BW ≥ 1000 g, eGFR remained constant. Other factors associated with decreased eGFR were hypertensive disorder of pregnancy (93.86 vs. 87.26 ml/min/1.73m2, P = 0.0285) in singletons, decreased growth velocity (β = 0.83, P = 0.0277) in twins, and lower total KV (tKV) and relative KV (rKV) in both singletons (r = 0.60, P < 0.0001 for tKV and r = 0.45, P = 0.0010 for rKV) and twins (β = 0.34, P < 0.0001 for tKV and β = 0.23, P = 0.0002 for rKV). Based on the multivariable models excluding KV, BW and gestational age were associated with eGFR in singletons, while male gender, BW, growth velocity, and coffee drinking during pregnancy were associated with eGFR in twins. However, in models that included KV, BW, gestational age and growth velocity were no longer significant. Total KV was associated with BW (r = 0.39, P = 0.0050 for singletons; β = 2.85, P < 0.0001 for twins), body mass index (r = 0.34, P = 0.0145 for singletons; β = 8.44, P < 0.0001 for twins), and growth velocity (β = 1.43, P = 0.0078). Twins born small for gestational age had lower tKV (70.88 vs 89.20 ml, P < 0.0001). Relative KV showed similar associations. Relative kidney volumes were significantly lower for both kidneys compared to the reference population (55.02 vs 65.42 ml/m2, P < 0.0001 for right kidney and 61.12 vs 66.25 ml/m2, P = 0.0015 for left kidney); however, only 8.6% of children had rKV below 10th percentile. CONCLUSION: Many factors affect eGFR and KV, some of them differ between twins and singletons. Based on multivariable models, eGFR seems to be better predicted by KV than by BW and gestational age in LBW children. Relative kidney volumes were significantly lower in our cohort compared to the reference population, but only 8.6% of rKV were below 10th percentile.
- MeSH
- Renal Insufficiency, Chronic epidemiology etiology physiopathology MeSH
- Twins MeSH
- Glomerular Filtration Rate * MeSH
- Kidney * diagnostic imaging physiopathology MeSH
- Humans MeSH
- Infant, Low Birth Weight * MeSH
- Infant, Newborn MeSH
- Birth Weight MeSH
- Child, Preschool MeSH
- Cross-Sectional Studies MeSH
- Risk Factors MeSH
- Pregnancy MeSH
- Organ Size MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
INTRODUCTION: The main goal of placenta accreta spectrum (PAS) screening is to enable delivery in an expert center in the presence of an experienced team at an appropriate time. Our study aimed to identify independent risk factors for emergency deliveries within the IS-PAS 2.0 database cohort and establish a multivariate predictive model. MATERIAL AND METHODS: A retrospective analysis of prospectively collected PAS cases from the IS-PAS database between January 2020 and June 2022 by 23 international expert centers was performed. All PAS cases (singleton and multiple pregnancies) managed according to local protocols were included. Individuals with emergent delivery were identified and compared to those with scheduled delivery. A multivariate analysis was conducted to identify the possible risk factors for emergency delivery and was used to establish a predictive model. Maternal outcomes were compared. RESULTS: Overall, 315 women were included in the study. Of these, 182 participants (89 with emergent and 93 with scheduled delivery) were included in the final analysis after exclusion of those with unsuspected PAS antenatally or who lacked information about the urgency of delivery. Gestational age at delivery was higher in the scheduled group (34.7 vs. 32.9, p < 0.001). Antenatal bleeding (OR 2.9, p = 0.02) and a placenta located over a uterine scar (OR 0.38, p = 0.001) were the independent predictive factors for emergent delivery (AUC 0.68). Ultrasound (US) markers: loss of clear zone (p = 0.001), placental lacunae (p = 0.01), placental bulge (p = 0.02), and presence of bridging vessels (p = 0.02) were more frequently documented in the scheduled group. None of these markers improved the predictive values of the model. Higher PAS grades were identified in the scheduled group (p = 0.01). There were no significant differences in maternal outcomes. CONCLUSIONS: Antenatal bleeding and the placental location away from the uterine scar remained the most significant predictors for emergent delivery among patients with PAS, even when combining more predictive risk factors, including US markers. Based on these results, patients who bleed antenatally may benefit from transfer to an expert center, as we found no differences in maternal outcomes between groups delivered in expert centers. Earlier-scheduled delivery is not supported due to the low predictive value of our model.
- MeSH
- Cesarean Section * statistics & numerical data MeSH
- Adult MeSH
- Humans MeSH
- Emergencies MeSH
- Placenta Accreta * diagnosis MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Pregnancy MeSH
- Delivery, Obstetric * statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Modulation of the cardiac autonomic nervous system (ANS) is a promising adjuvant therapy in the treatment of atrial fibrillation (AF). In pre-clinical models, pulsed field (PF) energy has the advantage of selectively ablating the epicardial ganglionated plexi (GP) that govern the ANS. This study aims to demonstrate the feasibility and safety of epicardial ablation of the GPs with PF during cardiac surgery with a primary efficacy outcome of prolongation of the atrial effective refractory period (AERP). METHODS: In a single-arm, prospective analysis, patients with or without a history of AF underwent epicardial GP ablation with PF during coronary artery bypass grafting (CABG). AERP was determined immediately pre- and post- GP ablation to assess cardiac ANS function. Holter monitors were performed to determine rhythm status and heart rate variability (HRV) at baseline and at 1-month post-procedure. RESULTS: Of 24 patients, 23 (96%) received the full ablation protocol. No device-related adverse effects were noted. GP ablation resulted in a 20.7 ± 19.9% extension in AERP (P < 0.001). Post-operative AF was observed in 7 (29%) patients. Holter monitoring demonstrated an increase in mean heart rate (74.0 ± 8.7 vs. 80.6 ± 12.3, P = 0.01). There were no significant changes in HRV. There were no study-related complications. CONCLUSIONS: This study demonstrates the safety and feasibility of epicardial ablation of the GP using PF to modulate the ANS during cardiac surgery. Large, randomized analyses are necessary to determine whether epicardial PF ablation can offer a meaningful impact on the cardiac ANS and reduce AF. TRIAL REGISTRATION: Clinical trial registration: NCT04775264.
- MeSH
- Electrocardiography, Ambulatory MeSH
- Electroporation * methods MeSH
- Atrial Fibrillation * surgery MeSH
- Ganglia, Autonomic * surgery MeSH
- Catheter Ablation * methods MeSH
- Coronary Artery Bypass * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Pericardium * surgery innervation MeSH
- Prospective Studies MeSH
- Aged MeSH
- Feasibility Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Study MeSH
BACKGROUND: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy. METHODS: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis. RESULTS: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%). CONCLUSIONS: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.
- MeSH
- Risk Assessment methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Multiparametric Magnetic Resonance Imaging * methods MeSH
- Prostatic Neoplasms * pathology diagnostic imaging diagnosis blood MeSH
- Prostate pathology diagnostic imaging MeSH
- Prostate-Specific Antigen * blood MeSH
- Retrospective Studies MeSH
- ROC Curve MeSH
- Aged MeSH
- Neoplasm Grading MeSH
- Image-Guided Biopsy methods MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: There is a paucity of data on treatment outcomes following stereotactic radiosurgery (SRS) for brain metastases from sarcoma primaries. METHODS: The International Radiosurgery Research Foundation member-sites were queried for patients with brain metastases from sarcoma primaries treated with SRS. Overall survival (OS) and local control (LC) were calculated via Kaplan-Meier analysis. Univariate analyses examined prognostic factors associated with LC and OS via log-rank t-tests and multivariate analyses (MVA) via Cox proportional hazards model. RESULTS: A total of 146 patients with 309 brain metastases were identified. Two-hundred and thirty lesions were treated with single-fraction SRS with a median dose of 20 Gy (15-24 Gy). Ninety-five patients had extracranial metastases, including 75 oligometastatic patients. One- and 2-year OS and LC rates were 47.7% and 37.3%, and 78.3% and 62.2%, respectively. On univariate analyses, superior 1-year OS was noted among leiomyosarcomas (69.7% vs. 42.6%; p = .02) with poorer outcomes among pleomorphic histologies (10.5% vs. 50.7%; p = .002). Pleomorphic histologies were associated with poorer OS on MVA (hazard ratio [HR], 3.13; p = .006). On MVA, LC was inferior among patients of age ≥45 years (HR, 3.78; p < .001) and superior among leiomyosarcomas (HR, 0.31; p = .03). OS was prognosticated based on adverse factors (ie, nonleiomyosarcoma histology and progressive extracranial metastases). Two-year OS for patients with and without adverse features were 78.6% and 31.5%, respectively. CONCLUSIONS: LC outcomes were driven by histology and age with superior LC among leiomyosarcomas and patients of age <45 years. OS was driven by nonleiomyosarcoma histology and the presence of progressive extracranial disease.
- MeSH
- Adult MeSH
- Kaplan-Meier Estimate MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Brain Neoplasms * secondary radiotherapy mortality surgery MeSH
- Prognosis MeSH
- Radiosurgery * methods MeSH
- Retrospective Studies MeSH
- Sarcoma * pathology mortality radiotherapy secondary MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Objective.Accurate localization of the epileptogenic zone (EZ) is crucial for epilepsy surgery, but the class imbalance of epileptogenic vs. non-epileptogenic electrode contacts in intracranial electroencephalography (iEEG) data poses significant challenges for automatic localization methods. This review evaluates methodologies for handling the class imbalance in EZ localization studies that use machine learning (ML).Approach.We systematically reviewed studies employing ML to localize the EZ from iEEG data, focusing on strategies for addressing class imbalance in data handling, algorithm design, and evaluation.Results.Out of 2,128 screened studies, 35 fulfilled the inclusion criteria. Across the studies, the iEEG contacts annotated as epileptogenic prior to automatic localization constituted a median of 18.34% of all contacts. However, many of these studies did not adequately address the class imbalance problem. Techniques such as data resampling and cost-sensitive learning were used to mitigate the class imbalance problem, but the chosen evaluation metrics often failed to account for it.Significance.Class imbalance significantly impacts the reliability of EZ localization models. More comprehensive management and innovative approaches are needed to enhance the robustness and clinical utility of these models. Addressing class imbalance in ML models for EZ localization will improve both the predictive performance and reliability of these models.
Major depressive disorder, particularly its treatment-resistant form (TRD), poses significant treatment challenges. Ketamine, an N-methyl-d-aspartate receptor antagonist, has shown promise in rapidly alleviating depressive symptoms by influencing neuroplasticity and glutamatergic modulation, which are thought to influence brain activity complexity. In this placebo-controlled study, we examined the effects of subanesthetic doses of intravenous ketamine on EEG signal complexity in 24 MDD patients, 21 of whom had TRD. Treatment response was defined by a ≥ 33 % reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) after ketamine administration. Patients underwent eyes-closed resting state EEG recording pre-, start-, end- and 24 h post-infusion, analyzed for temporospatial and spatiotemporal Lempel-Ziv complexity (LZCT and LZCS). Results indicated that ketamine significantly increased whole-brain LZCT during infusion compared to placebo (sodium chloride 0.9 %) (16.90 % vs. -4.84 %, 95 % CI 4.29 to 39.18, p = 0.017). Elevated LZCT at end-pre was associated with less short-term symptom improvement the following day. Conversely, lower pretreatment occipital LZCT (0.33 vs. 0.46, 95 % CI 0.007 to 0.26, p = 0.040) predicted a favorable response to ketamine, supported by a logistic regression model with an ROC area of 0.75. No significant changes were observed in LZCS, suggesting limited utility as a biomarker. In conclusion, occipital LZCT could serve as an effective predictive biomarker for ketamine's therapeutic effects in MDD, with implications for patients with TRD. This underscores the potential of EEG complexity measures in stratifying treatment and enhancing our understanding of the neural impacts of ketamine in depressive disorders.
- MeSH
- Excitatory Amino Acid Antagonists * administration & dosage pharmacology MeSH
- Depressive Disorder, Treatment-Resistant * drug therapy physiopathology MeSH
- Depressive Disorder, Major * drug therapy physiopathology MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Electroencephalography * drug effects MeSH
- Ketamine * administration & dosage pharmacology therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain * drug effects physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Controlled Clinical Trial MeSH
Cardiovascular diseases are associated with an altered cardiomyocyte metabolism. Because of a shortage of human heart tissue, experimental studies mostly rely on alternative approaches including animal and cell culture models. Since the use of isolated primary cardiomyocytes is limited, immortalized cardiomyocyte cell lines may represent a useful tool as they closely mimic human cardiomyocytes. This study is focused on the AC16 cell line generated from adult human ventricular cardiomyocytes. Despite an increasing number of studies employing AC16 cells, a comprehensive proteomic, bioenergetic, and oxygen-sensing characterization of proliferating vs. differentiated cells is still lacking. Here, we provide a comparison of these two stages, particularly emphasizing cell metabolism, mitochondrial function, and hypoxic signaling. Label-free quantitative mass spectrometry revealed a decrease in autophagy and cytoplasmic translation in differentiated AC16, confirming their phenotype. Cell differentiation led to global increase in mitochondrial proteins [e.g. oxidative phosphorylation (OXPHOS) proteins, TFAM, VWA8] reflected by elevated mitochondrial respiration. Fatty acid oxidation proteins were increased in differentiated cells, whereas the expression levels of proteins associated with fatty acid synthesis were unchanged and glycolytic proteins were decreased. There was a profound difference between proliferating and differentiated cells in their response to hypoxia and anoxia-reoxygenation. We conclude that AC16 differentiation leads to proteomic and metabolic shifts and altered cell response to oxygen deprivation. This underscores the requirement for proper selection of the particular differentiation state during experimental planning.NEW & NOTEWORTHY Proliferating and differentiated AC16 cell lines exhibit distinct proteomic and metabolic profiles with critical implications for experimental design. Proliferating cells predominantly utilize glycolysis and are highly sensitive to hypoxia, whereas differentiated cells display enhanced mitochondrial biogenesis, oxidative phosphorylation, and resistance to anoxia-reoxygenation. These findings provide novel insights into the metabolic adaptations during differentiation and highlight the necessity of selecting the appropriate cellular stage to ensure accurate experimental outcomes.
- MeSH
- Cell Differentiation * physiology MeSH
- Cell Line MeSH
- Energy Metabolism MeSH
- Cell Hypoxia physiology MeSH
- Myocytes, Cardiac * metabolism MeSH
- Humans MeSH
- Mitochondrial Proteins metabolism MeSH
- Mitochondria * metabolism MeSH
- Oxidative Phosphorylation MeSH
- Cell Proliferation MeSH
- Proteomics methods MeSH
- Signal Transduction * physiology MeSH
- Mitochondria, Heart * metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
