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15 pages, 3679 KB  
Systematic Review
Challenges of Salvage Holmium Laser Enucleation of the Prostate Following Contemporary Minimally Invasive Surgical Therapies for Benign Prostatic Hyperplasia: A Mixed-Methods Systematic Review with Meta-Analysis
by Kunind Oberoi, Sadia Hassan, Dan Lenaghan and Kapil Sethi
Soc. Int. Urol. J. 2026, 7(3), 34; https://doi.org/10.3390/siuj7030034 (registering DOI) - 16 Jun 2026
Abstract
Background/Objectives: Contemporary minimally invasive surgical therapies (MISTs) for benign prostatic hyperplasia carry retreatment rates up to 32%, with holmium laser enucleation of the prostate (HoLEP) increasingly used as salvage therapy. Prior reviews focused on salvage HoLEP (sHoLEP) following transurethral resection; however, technical challenges [...] Read more.
Background/Objectives: Contemporary minimally invasive surgical therapies (MISTs) for benign prostatic hyperplasia carry retreatment rates up to 32%, with holmium laser enucleation of the prostate (HoLEP) increasingly used as salvage therapy. Prior reviews focused on salvage HoLEP (sHoLEP) following transurethral resection; however, technical challenges specific to the post-MIST field remain uncharacterised. We aimed to characterise technical barriers during sHoLEP following contemporary MISTs, with secondary evaluation of efficacy, safety and feasibility. Methods: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines (PROSPERO: CRD420261321711), five databases were searched from inception to February 2026. Studies reporting sHoLEP outcomes in adults with prior MIST were included. Qualitative findings were synthesised thematically; quantitative outcomes reported by three or more studies underwent random-effects meta-analysis. Risk of bias was assessed using methodological index for non-randomized studies methodological index for non-randomized studies (MINORS) and certainty of evidence using grading of recommendations, assessment, development, and evaluation (GRADE). Results: Ten studies (354 sHoLEP, 3618 primary HoLEP (pHoLEP) patients) were included. Technical difficulty was MIST-type dependent: thermoablative procedures and prostatic artery embolisation preserved the enucleation plane, while prostatic urethral lift (PUL) introduced morcellation-specific challenges including blade jamming and staged procedures. Meta-analysis revealed no difference in operative time or tissue weight, but reduced enucleation efficiency (weighted mean difference; WMD −0.11 g/min, p = 0.027) and peak urinary flow improvement (WMD −3.0 mL/s, p < 0.001). Both findings were sensitive to analysis, losing significance on restriction to predominantly MIST cohorts, and the enucleation efficiency result additionally lost significance on removal of the most heavily weighted study (p = 0.94). Complication rates were equivalent (odds ratio (OR) 0.92, p = 0.787). Conclusions: sHoLEP is safe and efficacious following contemporary MIST. Surgeons should anticipate MIST-specific challenges, particularly morcellation difficulties after PUL requiring tailored instrumentation. Prospective MIST-specific studies are needed. Full article
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22 pages, 2987 KB  
Article
Serum Neuron-Specific Enolase as a Prognostic Biomarker in Pediatric Convulsive Status Epilepticus: A Single-Center Retrospective Cohort Study
by Merve Yavuz and Ibrahim Bingol
Children 2026, 13(6), 820; https://doi.org/10.3390/children13060820 (registering DOI) - 15 Jun 2026
Abstract
Background/Objectives: Serum neuron-specific enolase (NSE) is a biomarker of neuronal injury, but its prognostic role in pediatric convulsive status epilepticus (CSE) remains uncertain. We evaluated the association between serum NSE levels and short-term neurological outcome, assessed model calibration with internal bootstrap validation, and [...] Read more.
Background/Objectives: Serum neuron-specific enolase (NSE) is a biomarker of neuronal injury, but its prognostic role in pediatric convulsive status epilepticus (CSE) remains uncertain. We evaluated the association between serum NSE levels and short-term neurological outcome, assessed model calibration with internal bootstrap validation, and examined whether NSE provides incremental discrimination beyond established clinical severity scores. Methods: This was a single-center retrospective cohort study of children aged 1 month to 18 years admitted to a tertiary pediatric intensive care unit (PICU) with CSE as the primary admission diagnosis between January 2024 and November 2025. The primary outcome was poor neurological outcome at hospital discharge, defined as a worsening of ≥1 point in the Pediatric Cerebral Performance Category (PCPC) score from baseline (ΔPCPC ≥ 1) or in-hospital death. A multivariable logistic regression model adjusting for NSE, PRISM III, acute symptomatic etiology, and mechanical ventilation was developed, with bootstrap optimism-corrected internal validation (2000 resamples) and formal calibration assessment. Separate models for in-hospital mortality and for neurological deterioration among survivors were conducted as secondary analyses. Diagnostic operating characteristics were reported with 95% Wilson confidence intervals. The study followed the STROBE and TRIPOD reporting guidelines. Results: Of 132 children included (median age 26 months, 56.1% male), 60 (45.5%) had a poor neurological outcome including 18 deaths (13.6%). Serum NSE was significantly higher in the poor-outcome group (median 22.0 vs. 14.4 μg/L; p < 0.001). In the primary multivariable model, NSE (adjusted OR 1.11 per μg/L; 95% CI 1.06–1.19; p = 0.001) and PRISM III (adjusted OR 1.15; 95% CI 1.03–1.37; p = 0.013) were independently associated with poor outcome. The model showed acceptable calibration (Hosmer–Lemeshow p = 0.130) and a bootstrap optimism-corrected AUC of 0.759. NSE remained independently associated with both in-hospital mortality (aOR 1.13) and with ΔPCPC ≥ 1 in survivors (aOR 1.09). The AUC for NSE alone was 0.741 (95% CI 0.65–0.82) for poor outcome and 0.885 (0.79–0.96) for mortality. The combined PRISM III + NSE model showed a numerically higher but not statistically significant AUC compared with PRISM III alone (0.784 vs. 0.726; DeLong p = 0.103). Conclusions: Higher serum NSE is independently associated with adverse short-term neurological outcome and mortality in pediatric CSE, including in survivor-only analysis. However, the present data do not demonstrate clinically meaningful incremental prognostic value beyond PRISM III, and the proposed cutoff was derived and tested in the same cohort and is therefore optimistic. These findings are hypothesis-generating and require external validation in prospective multicenter cohorts with serial sampling and long-term neurodevelopmental follow-up before routine clinical use can be advocated. Full article
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38 pages, 2478 KB  
Article
Combined Effect of Per- and Polyfluoroalkyl Substances, Toxic Metals, Phthalates and Volatile Organic Compounds on Reproductive Hormones
by Issah Haruna and Emmanuel Obeng-Gyasi
Pollutants 2026, 6(2), 31; https://doi.org/10.3390/pollutants6020031 (registering DOI) - 15 Jun 2026
Abstract
Background: Human exposure to environmental endocrine-disrupting chemicals (EDCs) rarely occurs in isolation, yet most epidemiological research has assessed chemicals individually. PFASs, toxic metals, phthalates, and VOCs are ubiquitous contaminants with well-documented reproductive toxicity. Objective: The aim of this study was to investigate the [...] Read more.
Background: Human exposure to environmental endocrine-disrupting chemicals (EDCs) rarely occurs in isolation, yet most epidemiological research has assessed chemicals individually. PFASs, toxic metals, phthalates, and VOCs are ubiquitous contaminants with well-documented reproductive toxicity. Objective: The aim of this study was to investigate the joint and individual effects of 28 EDCs spanning four chemical classes on six reproductive hormone biomarkers in a nationally representative U.S. population—using an innovative approach that simultaneously characterizes nonlinear mixture effects and chemical interactions across multiple exposure domains. Methods: This cross-sectional study used NHANES 2017–2018 data (n = 9254). Multivariable linear regression and Bayesian Kernel Machine Regression (BKMR) characterized individual and mixture associations, respectively. Missing data were handled using multiple imputations by chained equations. Survey design weights were applied in linear regression models. Results: Linear regression revealed heterogeneous associations across chemical classes and hormones. PFOA was positively associated with SHBG (β = 12.35; 95% CI: 8.33, 16.38) and LH (β = 6.91; 95% CI: 1.44, 12.38), while mercury was inversely associated with estradiol (β = −3.38; 95% CI: −5.12, −1.65). BKMR analyses identified pronounced non-monotonic dose–response relationships and emergent mixture effects not predictable from single-chemical analyses for all six hormones. Posterior inclusion probabilities identified cadmium, PFOA, MEHP, and MBzP as the most influential predictors across hormone endpoints. Conclusions: Concurrent real-world exposure to PFASs, toxic metals, phthalates, and VOCs is associated with measurable, nonlinear alterations in reproductive hormone profiles. Chemical mixture effects cannot be reliably predicted from single-pollutant analyses, underscoring the necessity of mixture-based methodologies in environmental reproductive epidemiology. Prospective studies are needed to establish causal temporality and identify critical windows of susceptibility. Full article
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14 pages, 637 KB  
Article
Integrated Multimodal Critical Care Ultrasound for Mechanism-Based Prediction of Weaning Failure: A Prospective Pilot Study
by Şule Asri, Ferhat Soykan, Mustafa Ay and Dilara Tüfek Oztan
J. Clin. Med. 2026, 15(12), 4648; https://doi.org/10.3390/jcm15124648 (registering DOI) - 15 Jun 2026
Abstract
Background: Weaning from mechanical ventilation remains a complex and failure-prone process, with extubation failure rates reaching up to 30%. Conventional indices inadequately capture the multifactorial physiology underlying weaning failure. This study aimed to evaluate whether a multimodal ultrasound approach could improve the identification [...] Read more.
Background: Weaning from mechanical ventilation remains a complex and failure-prone process, with extubation failure rates reaching up to 30%. Conventional indices inadequately capture the multifactorial physiology underlying weaning failure. This study aimed to evaluate whether a multimodal ultrasound approach could improve the identification of mechanisms and prediction of extubation outcomes. Methods: In this prospective pilot observational study, adult mechanically ventilated patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) undergoing spontaneous breathing trials (SBT) were included. Multimodal ultrasound assessment—including transthoracic echocardiography (TTE), lung ultrasound (LUS), diaphragmatic ultrasound (DUS), and venous excess ultrasound (VExUS)—was performed at two predefined time points. Conventional respiratory mechanics parameters were recorded concurrently. The primary outcome was a composite of SBT failure (permanent weaning failure) or reintubation within 48 h. Results: A total of 27 patients were included, of whom 8 (29.6%) experienced extubation failure (5 permanent SBT failure, 3 post-extubation reintubation). Respiratory system compliance showed consistent associations with extubation failure across both ROC and regression analyses (AUC 0.806, 95% CI 0.611–1.000; cutoff ≤ 45 mL/cmH2O; sensitivity 88%; specificity 74%; NPV 93%). Diaphragm excursion was significantly lower in the failure group (p = 0.042) and showed useful predictive performance (AUC 0.750, 95% CI 0.565–0.935; cutoff ≤ 24 mm; sensitivity 100%; specificity 58%; NPV 100%). Lung ultrasound, VExUS, and echocardiographic parameters did not demonstrate significant predictive value. Given the limited number of outcome events (n = 8) and events-per-variable ratio of 4.0 (EPV = 4.0), all multivariable findings are hypothesis-generating. Conclusions: In this prospective pilot study, respiratory system compliance and diaphragm excursion were associated with extubation failure in patients with preserved left ventricular function, while echocardiographic indices, LUS, and VExUS grading did not demonstrate significant predictive value. These hypothesis-generating findings suggest that impaired diaphragmatic function and reduced compliance may be more closely associated with weaning failure than cardiopulmonary congestion parameters. However, given the small sample size, low EPV, and single-centre design, all findings require validation in larger multicentre studies including patients with impaired systolic function. Full article
(This article belongs to the Special Issue Ventilation in Critical Care Medicine: 2nd Edition)
14 pages, 3979 KB  
Article
Predicting Carotid Body Tumors’ Hardness via Multimodal Imaging: A Retrospective Cohort Study
by Jiazhi Yu, Kangxi Cao, Guangnan Ao, Yunfeng Han and Tao Wang
Diagnostics 2026, 16(12), 1852; https://doi.org/10.3390/diagnostics16121852 (registering DOI) - 15 Jun 2026
Abstract
Background: Carotid body tumors (CBTs) are rare neuroendocrine neoplasms whose hardness (soft vs. hard) correlates with surgical complexity and perioperative complications. This study aimed to identify predictive multimodal imaging biomarkers of CBTs’ hardness. Methods: This single-center retrospective cohort study included 82 [...] Read more.
Background: Carotid body tumors (CBTs) are rare neuroendocrine neoplasms whose hardness (soft vs. hard) correlates with surgical complexity and perioperative complications. This study aimed to identify predictive multimodal imaging biomarkers of CBTs’ hardness. Methods: This single-center retrospective cohort study included 82 patients with CBTs who underwent surgical resection. Preoperative multimodal imaging and clinical data were analyzed; tumor hardness was assessed via Masson-stained fibrous proportion. Multivariate logistic regression was performed to identify independent predictors. Results: The mean age of the 82 patients was 46 ± 13 years, including 37 males, with no significant intergroup differences in age or gender. Hard CBTs were associated with longer operative durations and a higher incidence of perioperative complications including pre-, intra-, and postoperative nerve and vascular injury. Multimodal imaging analysis revealed differences in signal homogeneity on T1WI and T1WI-CE sequences of MRI between soft and hard CBTs. The CBT-to-sternocleidomastoid muscle (SCM) value on T2WI (OR 0.329; 95% CI 0.151–0.591, p < 0.001) and the erosion of perivascular fat space (PFS) (OR 19.2; 95% CI 4.390–115.884, p < 0.001) were associated with the hardness of CBTs. ROC curve analysis demonstrated that an optimal cutoff value of 2.44 for the CBT/SCM ratio on T2WI predicted hard CBTs with a specificity of 100% and a sensitivity of 67.7% (PPV 100%, NPV 83.6%, AUC = 0.892). Conclusions: Preliminary findings suggest that CBT/SCM value on T2WI and PFS erosion are promising imaging biomarkers for predicting hardness. These parameters may facilitate preoperative risk prediction, though further prospective validation is required. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
11 pages, 447 KB  
Article
Leukocyte Telomere Length and Long-Term Clinical Outcomes in Women with Systemic Lupus Erythematosus: A Prospective Cohort Study
by Leyre Riancho-Zarrabeitia, Nuria Vegas-Revenga, Lucía C. Domínguez-Casas, Alfonso Corrales, Carolina Sañudo, Javier Riancho, Carmen Bejerano, Iñigo Gonzalez-Mazón and Ricardo Blanco
J. Clin. Med. 2026, 15(12), 4644; https://doi.org/10.3390/jcm15124644 (registering DOI) - 15 Jun 2026
Abstract
Background/Objectives: Leukocyte telomere length (TL) is a marker of biological aging associated with cardiovascular disease, chronic kidney disease, and malignancy in the general population. Its long-term prognostic significance in systemic lupus erythematosus (SLE) remains unclear. We aimed to evaluate the association between [...] Read more.
Background/Objectives: Leukocyte telomere length (TL) is a marker of biological aging associated with cardiovascular disease, chronic kidney disease, and malignancy in the general population. Its long-term prognostic significance in systemic lupus erythematosus (SLE) remains unclear. We aimed to evaluate the association between baseline TL and long-term clinical outcomes in patients with SLE. Methods: Prospective cohort study including 97 Caucasian women with SLE. Relative TL was measured in whole blood using quantitative polymerase chain reaction (qPCR) at baseline. A control group of 50 healthy Caucasian women from the same geographical region was included for comparison. Patients were followed for a mean of 9.7 ± 2.8 years. Outcomes included thrombotic cardiovascular events, damage accrual, incident malignancy, and chronic kidney disease. Associations were assessed using multivariable regression models adjusted for potential confounders. Results: Mean age was 51.6 ± 13.8 years and mean relative TL was 4.3 ± 1.0. Relative TL was inversely associated with age (β = −0.20, p = 0.048) and was shorter in patients with hematological manifestations (p = 0.038). No differences in relative TL were observed between SLE patients and controls. Relative TL was not associated with disease activity, cumulative damage, cardiovascular risk factors, vitamin D levels, or subclinical atherosclerosis. During follow-up, 13.4% of patients experienced cardiovascular events, 10.3% developed malignancy, and 11.3% developed chronic kidney disease. Relative TL was initially associated with long-term damage accrual, glomerular filtration rate and cardiovascular events; however, after adjustment for age, only the association with glomerular filtration rate remained at the limit of statistical significance (p = 0.05). Conclusions: In this prospective cohort, relative TL was primarily associated with aging, hematological manifestations, and glomerular filtration rate, but not with disease activity or most long-term clinical outcomes. These findings suggest that TL reflects biological aging rather than disease-specific processes and has limited utility as a prognostic biomarker in SLE. Full article
(This article belongs to the Section Immunology & Rheumatology)
13 pages, 1121 KB  
Article
Prognostic Value of Right Ventricular Performance and Left Atrial Mechanical Efficiency in Paroxysmal Atrial Fibrillation
by Aristi Boulmpou, Efstathios Pagourelias, Georgios Zormpas, Dimitrios Ntelios, Vassilios Vassilikos and Christodoulos Papadopoulos
J. Cardiovasc. Dev. Dis. 2026, 13(6), 269; https://doi.org/10.3390/jcdd13060269 (registering DOI) - 15 Jun 2026
Abstract
Background: Predicting atrial fibrillation (AF) recurrence remains a major clinical challenge, as conventional echocardiographic parameters often fail to capture the complex electro-mechanical substrate of the arrhythmia. The prognostic significance of right ventricular (RV) function and atrial mechanical–structural coupling in paroxysmal AF (PAF) [...] Read more.
Background: Predicting atrial fibrillation (AF) recurrence remains a major clinical challenge, as conventional echocardiographic parameters often fail to capture the complex electro-mechanical substrate of the arrhythmia. The prognostic significance of right ventricular (RV) function and atrial mechanical–structural coupling in paroxysmal AF (PAF) remains underexplored. Methods: We prospectively enrolled patients with PAF in sinus rhythm undergoing comprehensive echocardiography. A wide range of conventional left-sided, right-sided, and novel coupling indices was assessed. Univariable analysis was performed to screen for potential AF recurrence predictors. Based on the initial findings, receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff for RV fractional area change (RV FAC). Finally, multivariable logistic regression identified independent predictors of AF recurrence over a 12-month follow-up. Results: A total of 73 patients were included, of whom 31 (42.5%) experienced AF recurrence during 12-month follow-up. Conventional left atrial (LA) indices, including LA volume index (LAVI) and reservoir strain, showed no significant association with recurrence. In univariable analysis, RV FAC, LA contraction strain, and the novel LA contraction strain/LAVI ratio were all significant predictors. ROC analysis identified an RV FAC cutoff of 42.5%, with lower values associated with significantly higher recurrence rates. In multivariable analysis, lower RV systolic performance determined by RV FAC ≤ 42.5% emerged as a primary independent predictor of recurrence (p = 0.003), while the LA contraction strain/LAVI ratio demonstrated a strong trend towards significance (p = 0.076). Conclusions: In this exploratory study of patients with PAF, atrial mechanical–structural mismatch emerged as a primary marker of the arrhythmic substrate. Additionally, an exploratory signal suggested that a subclinical reduction in RV performance may also correlate with recurrence, though this warrants further investigation in larger cohorts. Full article
24 pages, 2596 KB  
Systematic Review
Adding Preoperative Oral Antibiotics to Mechanical Bowel Preparation Reduces Surgical Site Infections in Elective Colorectal Surgery: A Meta-Analysis of Randomized Controlled Trials
by Héctor Guadalajara, Alicia Putan, Mariano García Arranz, Miguel León-Arellano, Raquel Sanz-Baro, Jose Manuel Ramirez and Damián García-Olmo
Medicina 2026, 62(6), 1161; https://doi.org/10.3390/medicina62061161 (registering DOI) - 15 Jun 2026
Abstract
Background and Objectives: Surgical site infections (SSIs) remain common after elective colorectal surgery. This systematic review and meta-analysis evaluated whether adding oral antibiotic bowel preparation (OAB) to mechanical bowel preparation (MBP) reduces SSIs compared with MBP alone. Materials and Methods: PubMed, [...] Read more.
Background and Objectives: Surgical site infections (SSIs) remain common after elective colorectal surgery. This systematic review and meta-analysis evaluated whether adding oral antibiotic bowel preparation (OAB) to mechanical bowel preparation (MBP) reduces SSIs compared with MBP alone. Materials and Methods: PubMed, the Cochrane Library, Scopus, and ClinicalTrials.gov were searched for English-language randomized controlled trials published from January 2005 to January 2025. Eligible trials enrolled adults undergoing elective colorectal surgery and compared MBP+OAB versus MBP alone, with standard intravenous prophylaxis in both groups. The primary outcome was overall SSI; secondary outcomes were incisional SSI and organ-space SSI. Risk of bias was assessed with RoB 2, certainty with GRADE, and odds ratios (ORs) were pooled using DerSimonian–Laird random-effects models. The protocol was prespecified but not prospectively registered. Results: Twelve trials including 4073 patients were included (MBP+OAB, n = 2069; MBP, n = 2004). MBP+OAB reduced overall SSI (OR 0.53, 95% CI 0.37–0.75; p < 0.001; I2 = 62.5%; 95% prediction interval 0.17–1.66), incisional SSI (OR 0.52, 95% CI 0.34–0.80; p = 0.003; I2 = 57.5%), and organ-space SSI (OR 0.63, 95% CI 0.45–0.88; p = 0.007; I2 = 8.3%). The effect was preserved in metronidazole-containing regimens (OR 0.46, 95% CI 0.33–0.65), but this subgroup was exploratory. Excluding high-risk-of-bias studies supported the primary result. Publication-bias assessment was underpowered. Overall and organ-space SSI were moderate-certainty outcomes; incisional SSI was low-certainty, and anastomotic leak was very low-certainty. Conclusions: In contemporary elective colorectal surgery when MBP is used, adding preoperative OAB probably reduces SSIs. Findings do not establish whether OAB alone is sufficient or whether MBP is necessary; stewardship-relevant outcomes remain insufficiently reported. Funding was provided by ISCIII grant PI25/01285. Full article
(This article belongs to the Section Surgery)
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16 pages, 3242 KB  
Article
Sequential Helical–Axial–Helical Triple-Rule-Out CT Angiography: Technical Feasibility and Territory-Specific Image Quality in the Emergency Department
by Yeon-Jun Kim, Gi-Yong An, Sung-Jin Cha and Sung Min Ko
J. Clin. Med. 2026, 15(12), 4640; https://doi.org/10.3390/jcm15124640 (registering DOI) - 15 Jun 2026
Abstract
Background/Objectives: Triple-rule-out CT angiography (TRO-CTA) enables simultaneous evaluation of coronary, pulmonary, and aortic causes of acute chest pain, but conventional single-acquisition protocols may compromise vascular enhancement because of conflicting contrast timing requirements. This study evaluated whether a physiology-based sequential helical–axial–helical acquisition strategy could [...] Read more.
Background/Objectives: Triple-rule-out CT angiography (TRO-CTA) enables simultaneous evaluation of coronary, pulmonary, and aortic causes of acute chest pain, but conventional single-acquisition protocols may compromise vascular enhancement because of conflicting contrast timing requirements. This study evaluated whether a physiology-based sequential helical–axial–helical acquisition strategy could provide consistent tri-territory enhancement in emergency settings. Methods: In this retrospective single-center study, 71 consecutive evaluable emergency department patients (mean age, 66.6 ± 17.0 years; 33 women) with undifferentiated acute chest pain underwent TRO-CTA using a structured sequential protocol (pulmonary, coronary, and aortic phases) guided by individualized test-bolus timing. Objective image quality was assessed using vascular attenuation, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR); subjective image quality was independently graded by two radiologists. Results: Mean vascular attenuation exceeded predefined diagnostic thresholds in all territories (pulmonary 546.7 ± 237.8 HU [95% CI, 490.4–603.0]; coronary 438.8 ± 113.9 HU [95% CI, 411.9–465.8]; aortic 604.3 ± 190.9 HU [95% CI, 559.2–649.5]). Diagnostic interpretability was achieved in all three territories in every technically analyzable examination without repeat contrast-enhanced imaging. Median subjective image-quality scores were 5 (IQR, 4–5) for pulmonary, 4.5 (IQR, 4–5) for coronary, and 4 (IQR, 4–5) for aortic phases; interobserver agreement was good to excellent. Mean total DLP was 461.5 ± 122.5 mGy·cm. Conclusions: A sequential physiology-based TRO-CTA strategy is technically feasible in a tertiary emergency setting and provides consistent tri-territory enhancement. Because this was a single-arm technical validation study, prospective comparative and outcome-based studies are required to confirm its clinical impact. Full article
(This article belongs to the Special Issue Clinical Advances and Insights in Cardiovascular Imaging)
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14 pages, 1592 KB  
Article
Fecal Zonulin-Related Proteins in Inflammatory Bowel Disease: Associations with Clinical Disease Activity and Inflammatory Markers
by Sergiu Ioan Frandeș, Oana Frandeș, Melania Macarie, Claudiu Marinel Ionele and Simona Maria Bățagă
Medicina 2026, 62(6), 1160; https://doi.org/10.3390/medicina62061160 (registering DOI) - 15 Jun 2026
Abstract
Background and Objectives: Intestinal barrier dysfunction is increasingly recognized as a contributor to inflammatory bowel disease (IBD) pathophysiology. Zonulin, a regulator of epithelial tight-junction permeability, has emerged as a potential non-invasive biomarker; however, its clinical relevance remains uncertain. This study evaluated whether [...] Read more.
Background and Objectives: Intestinal barrier dysfunction is increasingly recognized as a contributor to inflammatory bowel disease (IBD) pathophysiology. Zonulin, a regulator of epithelial tight-junction permeability, has emerged as a potential non-invasive biomarker; however, its clinical relevance remains uncertain. This study evaluated whether fecal zonulin levels reflect clinical disease activity in inflammatory bowel disease and explored their association with ileal involvement in Crohn’s disease (CD). Materials and Methods: Forty-six consecutive IBD patients (26 CD, 20 UC) were prospectively included. Fecal zonulin was measured using a commercially available ELISA. In this study, the term “fecal zonulin” refers to ELISA-detected zonulin-related proteins. Clinical disease activity was assessed using CDAI for CD and the Mayo score for UC. Standard blood and fecal inflammatory markers were obtained, and subgroup analyses were performed according to disease type and location. Results: Fecal zonulin levels were significantly higher in active IBD compared with remission (106.37 vs. 53.80 ng/mL, p = 0.002). Patients with CD had higher zonulin concentrations than those with UC (91.4 vs. 51.0 ng/mL, p = 0.001). Zonulin showed a moderate positive correlation with fecal calprotectin (r = 0.338; p = 0.021). In multivariable analysis, clinical disease activity remained independently associated with zonulin levels, whereas ileal involvement was no longer statistically significant. Conclusions: Fecal zonulin is associated with disease activity in IBD, suggesting that fecal zonulin-related proteins may represent a potential adjunctive marker of epithelial barrier dysfunction and clinical disease activity in IBD. However, these findings should be considered exploratory and require validation in larger, longitudinal multicenter studies using standardized assays and endoscopic correlation. Full article
(This article belongs to the Special Issue New Advances in Inflammatory Bowel Disease and Diarrheal Disorders)
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18 pages, 986 KB  
Review
Advancing Insights into Biomarkers in Congenital Anomalies of the Kidney and Urinary Tract: A Scoping Review
by Francesco Maria Rosanio, Giulia Borgia, Elena Ferone, Adriano Braile, Seyedeh Fatemeh Hosseininasab and Mariantonia Braile
Cells 2026, 15(12), 1083; https://doi.org/10.3390/cells15121083 (registering DOI) - 15 Jun 2026
Abstract
Background: Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a heterogeneous spectrum of developmental disorders and represent the leading cause of chronic kidney disease and end-stage renal disease in the pediatric population. Although imaging remains the cornerstone of diagnosis, its limited [...] Read more.
Background: Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a heterogeneous spectrum of developmental disorders and represent the leading cause of chronic kidney disease and end-stage renal disease in the pediatric population. Although imaging remains the cornerstone of diagnosis, its limited ability to accurately assess disease severity and predict long-term outcomes has driven growing interest in urinary, serum, and tissue biomarkers as potential indicators of early renal injury. Objectives: To systematically summarize the current evidence on diagnostic and prognostic biomarkers in pediatric CAKUT, with particular focus on their potential clinical utility in early detection of renal injury and disease monitoring. Methods: A scoping review was conducted in accordance with PRISMA guidelines. PubMed, Embase, and Scopus were searched up to March 2026 using combinations of CAKUT-related terms and “biomarkers.” Studies involving human subjects with CAKUT that evaluated the diagnostic, prognostic, or therapeutic utility of biomarkers were included. Results: Out of 1130 records identified, 101 studies met the inclusion criteria. Urine was the most commonly analyzed biological sample. The principal biomarkers identified included NGAL, KIM-1, MCP-1, TGF-β1, CA19-9, β2-microglobulin, cystatin C, and microRNAs. Across various CAKUT subtypes—including posterior urethral valves, ureteropelvic junction obstruction, vesicoureteral reflux, and multicystic dysplastic kidney—these biomarkers showed significant associations with renal function, inflammatory activity, and fibrotic processes. Several biomarkers, particularly urinary NGAL, MCP-1, and CA19-9, demonstrated good diagnostic performance in differentiating obstructive from non-obstructive hydronephrosis and in predicting renal impairment. However, substantial heterogeneity in study design, along with the lack of standardized cutoff values, limits their translation into routine clinical practice. Conclusions: Current evidence underscores the potential of several biomarkers for the diagnosis and monitoring of CAKUT-related renal injury. Nevertheless, well-designed multicenter prospective studies are needed to validate their clinical utility and to support the integration of biomarker-based approaches with imaging in pediatric practice. Full article
(This article belongs to the Special Issue Kidney Disease: The Role of Cellular Mechanisms in Renal Pathology)
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9 pages, 507 KB  
Article
Relevance of Systematic Pre-Biologic Infectious Screening in Chronic Inflammatory Rheumatic Diseases: A Retrospective Single-Center Study
by Marie Doussiere, Clémence Jouret, Lara Awad, Pierre-Antoine Bruy, Laetitia Diep, Claire Jesson, Jean-Marc Sobhy-Danial, Franck Grados, Patrice Fardellone and Vincent Goëb
J. Clin. Med. 2026, 15(12), 4631; https://doi.org/10.3390/jcm15124631 (registering DOI) - 15 Jun 2026
Abstract
Background: Systematic infectious screening is recommended before initiation of biologic therapies in chronic inflammatory rheumatic diseases (CIRDs), yet the clinical impact of this strategy in low-prevalence settings remains insufficiently characterized. This study aimed to evaluate the proportion of abnormal findings and their impact [...] Read more.
Background: Systematic infectious screening is recommended before initiation of biologic therapies in chronic inflammatory rheumatic diseases (CIRDs), yet the clinical impact of this strategy in low-prevalence settings remains insufficiently characterized. This study aimed to evaluate the proportion of abnormal findings and their impact on treatment management. Methods: We conducted a retrospective single-center study including adult patients with CIRDs who underwent systematic pre-biologic infectious screening between January 2019 and June 2025. Screening included HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), interferon-γ release assay (IGRA), and chest radiography. The primary outcome was the proportion of abnormal results and their impact on biologic initiation. Results: A total of 418 patients was included (mean age 48.2 ± 14.6 years; 69.1% female). No active HIV, HBV, or HCV infections were detected. Past HBV infection markers were identified in 2.6% of patients, and anti-HCV antibodies in 0.7%, all without detectable viremia. None of these findings required modification of biologic therapy. IGRA positivity was observed in 4.3% of patients and indeterminate results were seen in 3.1%. Preventive antituberculous therapy was initiated in most newly identified IGRA-positive cases, leading to delayed biologic initiation in several patients. Chest radiography yielded limited additional diagnostic value. Conclusions: In this population, systematic pre-biologic infectious screening identified few clinically actionable viral infections, whereas latent tuberculosis screening represented the main determinant of therapeutic modification. These findings support continued emphasis on tuberculosis risk assessment and warrant further prospective studies to evaluate optimized and potentially targeted screening strategies incorporating cost-effectiveness analyses. Full article
(This article belongs to the Special Issue Preventive Strategies and Novel Treatments for Rheumatoid Arthritis)
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16 pages, 3730 KB  
Article
Persistent CRP Elevation at 4 Weeks Is Associated with Delayed Union After Polytrauma: An Exploratory Retrospective Cohort Study
by Eduard Catalin Georgescu, Ioana Anca Badarau, Alexandru Lisias Dimitriu, Elisa Georgiana Popescu, Monica Georgiana Roman, Liliana Mirea, Dragos Ene and Razvan Ene
Diagnostics 2026, 16(12), 1845; https://doi.org/10.3390/diagnostics16121845 (registering DOI) - 15 Jun 2026
Abstract
Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union [...] Read more.
Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union in polytrauma patients with long-bone fractures. Methods: We performed an exploratory retrospective cohort study including 115 adult polytrauma patients with long-bone fractures treated at a single tertiary trauma center between 2 January 2022 and 14 December 2024. Serum IL-6, CRP, and fibrinogen were recorded at 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after injury. IL-6 was measured in the institutional clinical laboratory using routine immunoassay methods, whereas CRP and fibrinogen were measured using standard hospital analytical methods, including an immunoturbidimetric assay for CRP and the Clauss clotting method for fibrinogen. Radiographic healing was assessed at 6, 12, and 24 weeks using an mRUST-based healing score. The primary endpoint was clinician-assigned delayed union at 24 weeks; nonunion at 9 months was assessed secondarily. Complete-case multivariable logistic regression was performed in 86 patients, and exploratory longitudinal biomarker analyses used generalized estimating equations. Results: Delayed union at 24 weeks occurred in 39/115 patients (33.9%), while nonunion at 9 months occurred in 7/115 patients (6.1%). Patients with delayed union had longer time to definitive fixation (35.3 ± 10.2 h vs. 29.0 ± 14.0 h; p = 0.003) and more frequent shock on admission (43.6% vs. 23.7%; p = 0.047). IL-6 was higher in the delayed-union group at 1 week (57.3 ± 30.3 vs. 46.5 ± 29.2 pg/mL; p = 0.043) and 4 weeks (21.2 ± 11.6 vs. 17.1 ± 10.3 pg/mL; p = 0.022), whereas CRP was markedly higher at 4 weeks (29.4 ± 14.2 vs. 16.3 ± 10.6 mg/L; p < 0.001). After false-discovery-rate correction, only CRP at 4 weeks remained significant among serial biomarker comparisons. In multivariable analysis of 86 complete cases, CRP at 4 weeks remained independently associated with delayed union (adjusted OR 2.16 per 10 mg/L, 95% CI 1.36–3.43; p = 0.001). The model showed apparent discrimination with an AUC of 0.80 and acceptable calibration (Hosmer–Lemeshow p = 0.41). In sensitivity analysis excluding deep surgical-site infection cases, the association between CRP and delayed union persisted (adjusted OR 2.02 per 10 mg/L, 95% CI 1.26–3.26; p = 0.004). Conclusions: In this exploratory retrospective cohort of polytrauma patients with long-bone fractures, persistent post-traumatic CRP elevation at 4 weeks was associated with clinician-assigned delayed union, whereas IL-6 findings were weaker and exploratory. Because CRP is a nonspecific inflammatory marker, the observed association may reflect delayed healing, infection, reoperation, and/or persistent postoperative inflammatory burden. These data support association rather than validated prediction and require prospective validation with standardized outcome adjudication. Full article
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22 pages, 1247 KB  
Article
Home Fetal Heart Rate Monitoring in Pregnancy: Patient Experience and Acceptance in the Era of Digital Prenatal Care
by Sidonia Maria Săndulescu, Virginia Maria Rădulescu, Sidonia Cătălina Vrabie, Anca Vulcănescu, Andreea Velișcu Carp, Mirela Anișoara Siminel, George Lucian Zorilă, Ioana Victoria Camen, Laurențiu Dîră, Bogdan Ivănuș, Claudia Monica Danilescu and Maria-Magdalena Manolea
Healthcare 2026, 14(12), 1702; https://doi.org/10.3390/healthcare14121702 (registering DOI) - 15 Jun 2026
Abstract
Background: Digital health technologies have expanded access to home fetal heart rate (FHR) monitoring devices, enabling fetal surveillance outside clinical settings. However, evidence on women’s awareness, acceptance, and experiences with these devices remains limited. Objective: To assess awareness, adoption, user experience, [...] Read more.
Background: Digital health technologies have expanded access to home fetal heart rate (FHR) monitoring devices, enabling fetal surveillance outside clinical settings. However, evidence on women’s awareness, acceptance, and experiences with these devices remains limited. Objective: To assess awareness, adoption, user experience, perceived reassurance, and attitudes toward home FHR monitoring among pregnant and postpartum women. Methods: A cross-sectional online survey was conducted using a structured questionnaire distributed via Google Forms. Eligible participants were women aged ≥18 years who were currently pregnant or had been pregnant within the previous two years. The survey evaluated awareness and use of home FHR monitoring devices, usage patterns, sources of recommendation and instruction, emotional responses, perceived reassurance, mobile application integration, and overall attitudes. Descriptive statistics and exploratory subgroup analyses were performed. Results: A total of 225 women completed the survey; 166 (73.8%) reported using a home FHR monitoring device during pregnancy. Most users reported positive emotional experiences, with calmness as the most common response. Home monitoring was generally perceived as reassuring, and many participants felt calmer on days of device use. Gynecologists were the primary source of device recommendations and usage instructions. Participants highlighted the importance of professional guidance, clear instructions, and mobile application support. Primiparous women had significantly higher adoption rates than multiparous women (p < 0.001). Conclusions: Home FHR monitoring was widely accepted and commonly perceived as reassuring. These devices may support patient-centered prenatal care when accompanied by appropriate professional guidance. Further prospective studies are needed to assess their clinical utility, safety, and integration into prenatal care pathways. Full article
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12 pages, 2607 KB  
Article
The Role of 3D/4D Transperineal Ultrasound in Risk Stratification for Pelvic Organ Prolapse Recurrence: Native Tissue Versus Mesh Repair
by José Antonio García-Mejido, María José Nuñez-Matas, Olaya Salas-Álvarez, Alejandro Crespo-Rodriguez, Ana Fernández-Palacín and José Antonio Sainz-Bueno
J. Clin. Med. 2026, 15(12), 4627; https://doi.org/10.3390/jcm15124627 (registering DOI) - 14 Jun 2026
Abstract
Background/Objectives: Pelvic organ prolapse (POP) management requires precise patient selection for surgical techniques to balance clinical efficacy and safety. The primary aim of this study was to evaluate the role of preoperative 3D/4D transperineal ultrasound in the risk stratification of POP recurrence. [...] Read more.
Background/Objectives: Pelvic organ prolapse (POP) management requires precise patient selection for surgical techniques to balance clinical efficacy and safety. The primary aim of this study was to evaluate the role of preoperative 3D/4D transperineal ultrasound in the risk stratification of POP recurrence. We analyzed the impact of levator ani muscle (LAM) injuries, specifically avulsion and ballooning, as identified by ultrasound, on both anatomical and subjective success rates, comparing native tissue repair versus mesh-augmented surgery. Methods: A prospective, multicenter observational study was conducted over a five-year period, January 2021 to December 2024 (recruitment), with follow-up completed in December 2025, ensuring a minimum follow-up of 12 months for all participants. The cohort included 276 women scheduled for primary surgery for symptomatic POP stage ≥ 2. Prior to intervention (116 underwent native tissue repair and 160 received mesh), all patients underwent 3D/4D transperineal ultrasound for standardized volume acquisition. Using this preoperative functional imaging technique, we measured the hiatal area and diagnosed the presence of hiatal ballooning (≥25.0 cm2) or levator muscle avulsion. Results: Ultrasound assessment revealed significant differences in surgical success based on the diagnosed baseline site-specific defects. Hiatal ballooning was the sonographic finding that demonstrated the greatest impact on risk stratification. Among patients with preoperative ballooning, mesh use significantly reduced both subjective recurrence (5.7% vs. 21.4%, p = 0.001) and objective recurrence (21.4% vs. 35.7%, p = 0.040) compared to native tissue repair. Furthermore, in women without ultrasound-documented avulsion, mesh also decreased objective recurrence (17.9% vs. 33.0%, p = 0.024). Multivariate analysis, adjusted for age, BMI, menopausal status, and parity, confirmed that, after stratifying by these preoperative ultrasound findings, a native tissue approach remains the primary independent predictor of surgical failure (OR 1.752 for objective recurrence; p = 0.041). Conclusions: In conclusion, native tissue repair was identified as the primary independent predictor of surgical failure. While 3D/4D transperineal ultrasound helps identify high-risk phenotypes such as hiatal ballooning, these sonographic findings did not maintain independent significance in the multivariate model. Therefore, ultrasound should be considered a complementary tool for surgical planning rather than a definitive predictor of recurrence. Full article
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