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Multiple studies have shown that symptom-based subtypes of obstructive sleep apnea (OSA) exist and are generalizable to clinical and population-based samples of different race/ethnic and regional backgrounds. However, there have not been studies evaluating the generalizability within a clinical sample of Chinese ancestry. Thus, the aim of the current study was to investigate the generalizability of symptom-based subtypes within clinical patients from China. This is a cross-sectional, multi-center study of patients with OSA from international sleep centers participating in the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Two Chinese cohorts were collected: 666 patients from Peking University People's Hospital (PKUPH) and 503 patients from other China sites (Peking University International Hospital, Taiwan, and Shanghai). In addition, 694 White patients were included from 7 sites across 5 countries (Iceland, Germany [Berlin], Australia [Sydney, Perth], Brazil, and the United States [Ohio State University and University of Pennsylvania]). Symptom-based subtypes were determined using a latent class analysis (LCA) of 18 self-reported symptom variables and 3 comorbidities. A total of 1,863 patients were included in the LCA. The previously described 5 symptom subtype (disturbed sleep, minimal symptoms, excessively sleepy, moderately sleepy, and upper airway symptoms dominant) were optimal in the PKUPH site, other China sites, and White patients from SAGIC. Chinese patients had higher prevalence of the minimal symptoms subtype (P < .001) compared to White patients. Among the five subtypes, the excessively sleepy subtype exhibited the highest AHI, and ODI. : Based on the included symptoms and comorbidities, five subtypes provided the optimal groupings across both Chinese and White patients in SAGIC. Chinese patients were more likely to present with fewer symptoms. These data further enhance understanding of the generalizability of OSA symptom subtypes across ethnically diverse backgrounds, and pave the way for precision management of OSA in the future.
Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin and is approved for adolescents and adults with severe asthma. This analysis assessed pharmacokinetics (PK), pharmacodynamics and safety of tezepelumab up to 85 days postdose in adolescents and children. The adolescent PK study (NCT02512900), in adolescents aged 12-17 years with mild-to-moderate asthma, and TRAILHEAD (NCT04673630), in children aged 5-11 years with mild, moderate or severe asthma, were both open-label, single-dose, Phase 1 studies. In the adolescent PK study, 21 adolescents (median age: 14 years) received a single 140-mg subcutaneous tezepelumab dose. The mean maximum concentration (Cmax; 24.0 [SD: 6.6] μg/mL) was observed at a median time of 6 (range: 1-20) days postdose, with a mean terminal half-life of 25.3 (SD: 4.7) days. The mean area under the concentration-time curve (AUC0-infinity) was 952 (SD: 289) μg*day/mL. In TRAILHEAD, 18 children (median age: 8 years) received a single 70-mg subcutaneous tezepelumab dose. The Cmax (27.1 μg/mL [SD: 11.9]) was observed at a median time of 3.5 (range: 2-10) days postdose, with a mean terminal half-life of 25.7 (SD: 5.9) days. The mean AUC0-infinity was 974 (SD: 320) μg*day/mL. Changes from baseline in blood eosinophil count, fractional exhaled nitric oxide and serum immunoglobulin E (IgE) reflected expected pharmacodynamic effects of tezepelumab. No new safety signals were identified. These results were consistent with previous studies of tezepelumab in other groups, supporting development of tezepelumab for asthma in the paediatric population.
Drowning remains a substantial global health challenge, and research in this area predominantly relies on observational study designs due to ethical, practical and administrative limitations. Although the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement is available, adherence within the drowning research community has been inconsistent and frequently incomplete. Consequently, essential methodological components and drowning-specific factors are often under-reported or inconsistently described, impeding quality, reproducibility, critical appraisal and evidence synthesis. This protocol outlines the development of an extension to the STROBE statement, specifically for reporting observational studies in drowning epidemiology (STROBE-D). The proposed extension aims to provide structured guidance for authors, reviewers and editors, thereby enhancing the clarity, transparency and comparability of reporting practices. The development of the STROBE-D statement will follow established recommendations and methodological frameworks for guideline creation. The process will include a scoping review and initial draft preparation, a two-round modified Delphi process using surveys with multidisciplinary and international expert participation, an expert consensus meeting to finalise the content and manuscript, public comment with interest-holder involvement and a final revision before submission for peer review. The Committee on Health Research Ethics in the Region Zealand of Denmark waived the need for ethical approval as this is a consensus study (EMN-2025-09099). Findings will be disseminated through open access peer-reviewed publications, targeted communication through professional networks, conferences and social media platforms. The STROBE-D statement will serve as an extension to the STROBE statement, specifically tailored to observational studies in drowning epidemiology to improve consistency and transparency. Simultaneous publications of the original STROBE-D statement and the accompanying explanation and elaboration paper will be pursued in line with existing best practices.
Minimally invasive surgery is rapidly expanding globally, yet there is insufficient knowledge of how to scale this technology safely and equitably across diverse health systems. We aimed to identify health-system factors associated with safe implementation of minimally invasive surgery globally, using minimally invasive cholecystectomy as a tracer procedure. We conducted a multicentre, prospective cohort study of consecutive adults undergoing cholecystectomy between July 31 and Nov 19, 2023, in 1218 hospitals across 109 countries. Data were collected by more than 10 000 health-care workers using a core measurement set mapped to the WHO Health System Building Blocks and the Global Patient Safety Action Plan. The primary outcome was 30-day procedure-specific complications, with multilevel logistic regression used to examine associations between health-system features and patient outcomes. This study is registered on ClinicalTrials.gov (NCT06223061). Among 52 187 included patients, the adjusted procedure-specific complication rate varied 40-fold between hospitals, from 0·3% in the lowest risk quintile to 12·1% in the highest risk quintile. Despite large structural differences across income groups in access to minimally invasive surgery, diagnostics, and emergency services, country income level was not independently associated with complication rates (adjusted odds ratio [OR] 0·81 [95% CI 0·59-1·10] for upper-middle income vs high income and 0·99 [0·70-1·39] for lower-middle income or low income vs high income). Three modifiable hospital-level factors were strongly associated with safer outcomes: establishment of local simulation-based training facilities (adjusted OR 0·78 [0·71-0·86]; p<0·0001), adoption of intraoperative safety and communication strategies (0·87 [0·79-0·96]; p=0·0046), and on-site CT diagnostics (0·79 [0·65-0·97]; p=0·0220). Training facilities showed the greatest benefit in hospitals with limited infrastructure and an inexperienced workforce: the number needed to treat to prevent a procedure-specific complication was 21 (95% CI 14-35; p<0·0001). Safe implementation of minimally invasive surgery varies widely worldwide but is not defined by national income level; differences in outcomes reflect the ability of health systems to adopt and safely deploy new surgical techniques. We identified for the first time that the presence of local simulation-based training facilities is independently associated with improved patient outcomes. Simulation appears to be fundamental to the safe delivery of minimally invasive surgery, particularly in resource-constrained settings. Together with safety systems and diagnostic capacity, these findings offer actionable targets for health systems seeking to equitably scale up essential surgical technologies. NIHR Global Health Research Unit and Wellcome Leap SAVE Programme.
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The phenotypic nature of multimorbidity in severe asthma is poorly understood. Our aims in this study were to define multimorbidity phenotypes and their characteristics in severe asthma across Europe by identifying and characterising co-aggregation of comorbidities. Cross-sectional patient data were analysed from the pan-European Severe Heterogenous Asthma Research Collaboration: Patient Centred (SHARP) Central database of national severe asthma registries. Patients were grouped by four European regions (North, South, East, and West). Hierarchical clustering of comorbidities was applied to characterise the correlation structure of the ten commonest comorbidities within these geographical regions. Subsequent multimorbidity phenotypes (MMP) and their clinical features were then defined. Data were available for 2690 severe asthma patients and 23 comorbidities from 11 countries. Three comorbidity clusters were consistently seen across the four European regions: 1) osteoporosis plus steroid-induced weight gain, 2) eczema plus rhinitis, and 3) chronic sinusitis plus nasal polyps. Four further comorbidities (obesity, bronchiectasis, gastro-oesophageal reflux disease, psychological factors) showed variable clustering. Multimorbidity was ubiquitous. Patients were assigned multimorbidity phenotypes (MMP) according to comorbidity cluster alignment. MMP sn (sinonasal-associated) and MMP u (no specific cluster alignment) were commonest. MMP ster (steroid-associated multimorbidity) had highest maintenance oral steroid (m-OCS) use, and Body Mass Index, plus worst lung function, asthma control, and asthma exacerbation frequency. MMP max (maximal multimorbidity) showed high prevalence of variably assigned comorbidities, higher m-OCS and biologic treatment needs. Multimorbidity is common in severe asthma and can be classified into replicable novel phenotypes with characteristic clinical traits and outcomes. Recognising these phenotypes can guide better care of the 'whole patient' with severe asthma. Future clinical guidance should promote such understanding in order to support delivery of more effective personalised asthma care. European Respiratory Society, pharmaceutical industry partners (Sanofi, TEVA, Novartis, GlaxoSmithKline, Chiesi).
Background: Innovative training strategies aimed at improving physiological efficiency are of growing interest in kinesiology and sports performance. Elevation training masks (ETMs) offer a practical means of inducing hypoxia-like stress. However, evidence of their effectiveness in recreationally active populations remains limited. This pilot study examined the efficiency of a five-week progressive ETM protocol combined with high-intensity interval training (HIIT) in eliciting physiological, hematological, and body-composition adaptations relevant to endurance performance. Methods: Nine recreationally active men completed a five-week intervention consisting of three treadmill-based sessions per week: one weekly incremental Conconi test and two structured aerobic-anaerobic HIIT sessions performed with an ETM. Mask resistance was progressively increased to simulate altitudes of approximately 900-3600 m. Hematological variables (erythrocytes, hemoglobin, hematocrit, erythrocyte indices, leukocytes, and platelets), body composition, maximal heart rate (HRmax), and peripheral oxygen saturation (SpO2) were assessed pre- and post intervention. Data were analyzed using paired-sample t-tests and repeated-measures ANOVA, with effect sizes reported (Cohen's d, ω2). Results: A significant main effect of time on SpO2 was observed (F(1, 8) = 130.61, p < 0.001, ω2 = 0.69), along with a significant effect of training week (F(4, 32) = 17.41, p < 0.001, ω2 = 0.43), and a significant Time × Week interaction (F(4, 32) = 15.20, p < 0.001, ω2 = 0.42), indicating progressively greater post-exercise oxygen desaturation with increasing simulated altitude. Significant post-intervention increases were found in erythrocyte count, hemoglobin concentration, and hematocrit (p ≤ 0.009, d = 1.15-1.55), alongside increases in mean corpuscular volume and mean corpuscular hemoglobin. Platelet count increased significantly (p = 0.001, d = 1.68), while leukocyte values remained unchanged (p > 0.05). Body mass index (p = 0.049, d = 0.77) and body fat percentage (p = 0.012, d = 1.08) decreased following the intervention. HRmax tended to be lower at higher simulated altitudes. Conclusions: A five-week progressive ETM-HIIT protocol efficiently induced hematological and body-composition adaptations associated with improved oxygen transport and metabolic efficiency in recreationally active men. These findings support ETM-based training as an accessible strategy for enhancing physiological efficiency in endurance-oriented kinesiology practice, warranting confirmation in larger randomized controlled studies.
Having appropriate and meaningful diagnostic procedures is crucial in the approach to patients with chronic spontaneous urticaria (CSU), so we wanted to investigate relationships between CSU patients' common serum factors and clinical CSU features, and their temporal trends during antihistamine treatment. In this exploratory hypothesis-based study, we assessed disease severity and quality of life (QoL) in, initially, 41 CSU patients using UAS7, daily UAS, UCT, DLQI, and CU-Q2oL. Concurrently, we measured serum complete blood count (CBC), total IgE, thyroid antibodies and hormones, ANA, D-dimer, vitamin D, and the inflammatory molecules CRP, ESR and IL-6. We compared initial (T1) and follow-up findings (T2) (after 3 months of antihistamine therapy). Basophil concentration was the only examined serum factor useful in assessing current CSU severity/daily UAS (sensitivity 78.6%; specificity 63%; p = 0.028). Basopenia was more frequent in patients with moderate/severe CSU than in those with mild disease or remission, as measured by daily UAS (79% vs. 37%; p = 0.020). T4 values showed a significant dependence on CSU duration (r = -0.328; p = 0.036). ESR was the only examined serum factor significantly associated with weekly CSU severity (UAS7) (p = 0.038). Antihistamine treatment significantly reduced CSU activity (recorded by daily UAS and UAS7) and improved QoL (DLQI) (p = 0.006) and disease control/UCT (p = 0.005). After three months of treatment, only the CRP value correlated with CSU control/UCT (p = 0.014). We encourage the use of diagnostics employing basophil counts and clinical indices UAS7, daily UAS, UCT and DLQI for insight into a patient's CSU clinical condition. Serum factor values did not change during the 3-month treatment period, so it is not useful to measure them repeatedly. Although this study involved a small cohort and has many limitations, these promising results highlight the need for replication with a greater number of CSU patients.
Oral and ocular medications are frequently used in the treatment of allergic rhinitis (AR). As part of the update of the Allergic Rhinitis and its Impact on Asthma (ARIA)-EAACI guidelines, this manuscript presents the ARIA-EAACI 2024-2025 recommendations for oral and ocular treatments. The ARIA-EAACI 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgements and recommendations, including systematic reviews, mHealth and pharmacovigilance data as well as a survey on costs. Eight guideline questions concerning oral treatments for AR and three questions concerning ocular treatments were addressed. These questions led to the recommendations. Overall, these questions concern the choice between different classes of medication. They also discuss the role of oral antihistamines (OAH), leukotriene receptor antagonists (LTRA), ocular antihistamines (OcAH) and ocular mast cell stabilisers. Four questions had not been previously evaluated in ARIA guidelines, while, for the other four, there was a change in the strength or directionality of the recommendations. Overall, these guidelines recommend using intranasal corticosteroids over OAH and using OAH over LTRA. Moreover, they suggest using OAH over OcAH and suggest being against adding LTRA to OAH. Finally, considerations for choosing between different individual OAHs are presented. This ARIA-EAACI 2024-2025 article supports patients, their caregivers and healthcare professionals in choosing oral and ocular treatments for AR. Decisions on treatment should consider the clinical variability of the disease, patients' values and the affordability of medications.
Limited data are available on long-term outcomes after percutaneous coronary intervention (PCI) of coronary drug-eluting stent (DES) in-stent restenosis (ISR) depending on clinical presentation with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS). Thus, the aim of this observational, retrospective study was to address this lack of evidence. Between January 2007 and February 2021, a total of 3,511 patients with 5,497 ISR lesions were treated at 2 large-volume centers in Munich, Germany, of which 1,029 (29.3%) were treated for ACS. Endpoints of interest were the rates of cardiac death, myocardial infarction (MI), repeat revascularization, and stent thrombosis (ST). Survival was analyzed using the Kaplan-Meier method. Differences between the groups were tested with the log-rank test. Conventional multivariable analysis with adjustment for relevant variables was performed. After ten years, the rates of cardiac death were 42.5% in patients with ACS and 33.3% in patients with CCS (HR 1.63 [95% CI, 1.41-1.88], p < 0.001). 17.4% of ACS patients and 9.5% of CCS patients experienced MI (HR 2.04 [95% CI, 1.65-2.50], p < 0.001). The rates of ST were 3.6% in patients with ACS and 1.2% in patients with CCS (HR 3.18 [95% CI, 1.92-5.24], p < 0.001). The rates of repeat revascularization of target lesion, target vessel and non-target vessel did not differ significantly between both groups in the long-term. In the long-term, the rates of cardiac death, MI and ST after PCI of DES-ISR are significantly higher in ACS patients than in CCS patients.
Rapid urbanisation in India has intensified stress on urban water systems, where inadequate sewage treatment, intermittent distribution, and fragmented governance compromise drinking-water quality across diverse city typologies. These weaknesses disproportionately affect informal settlements, increasing exposure to microbial contamination and chronic toxicants such as nitrate, fluoride, arsenic, and industrial pollutants. Beyond acute infections, growing evidence suggests that urban aquatic environments function as amplification reservoirs for antimicrobial resistance. This perspective synthesises evidence across water, sanitation, environmental surveillance, and health systems to examine how infrastructure gaps and weak integration with public health monitoring sustain preventable disease burdens. It reframes urban water quality as a public health function rather than solely a municipal service, highlighting the limits of infrastructure-centric metrics. Pragmatic interventions, including continuous pressurised supply, strengthened sewage and effluent control, integrated water-quality and disease surveillance, and explicit linkage to AMR containments, should be prioritised, with success measured through reductions in morbidity and resistance.
4-hydroxy-TEMPO is a water-soluble nitroxide radical with potent antioxidant and redox-modulating properties. Its small molecular weight and membrane permeability enable it to act as a superoxide dismutase mimetic, efficiently scavenging reactive oxygen species and mitigating oxidative damage. In this study, we investigated the physiological and transcriptomic effects of 4-hydroxy-TEMPO in Saccharomyces cerevisiae, using wild-type and mutant strains deficient in key redox and DNA repair pathways (sod1Δ, sod2Δ, yap1Δ, rad52Δ). RNA-Seq analysis revealed widespread transcriptional reprogramming. Treatment with 4-hydroxy-TEMPO impaired cell growth, induced accumulation of cells with 1C (G1 phase) DNA content, and modulated chronological aging in a strain-dependent manner. Notably, low concentrations delayed aging in wild-type, yap1Δ, and rad52Δ strains, while accelerating it in sod1Δ mutants, consistent with a hormetic response. Unlike TEMPO, 4-hydroxy-TEMPO exhibited markedly reduced translational toxicity, preserved polysome structure at high doses, and triggered a non-canonical, redox-dependent transcriptional program characterized by induction of stress-response genes together with unexpected up-regulation of multiple ribosomal protein genes. This was accompanied by a biphasic, genotype-specific hormetic response and a measurable genoprotective effect. RT-qPCR confirmed key transcriptional changes, linking transcriptome remodeling to functional outcomes.
Cellular metabolism within follicle continuously generates reactive oxygen species (ROS). This study aimed to investigate the biochemical composition related to redox homeostasis, inflammatory markers, and microelements in follicular fluid (FF) of women with idiopathic infertility. Additionally, it sought to compare these parameters among: (i) modified natural cycles (mNC) and controlled ovarian stimulation (COS), (ii) fertilization success, and (iii) IVF outcome. Follicular fluid samples were collected from women undergoing mNC as well as COS using gonadotropin-releasing hormone (GnRH) antagonists. Follicular fluid analysis included measuring the concentrations of: malondialdehyde, 15-F2t-isoprostane, vitamin E, and the total activity of superoxide dismutase (SOD). Microelements, copper and zinc, were measured, along with the inflammation marker interleukin 6. A total of 60 women under the age of 42, participated in the study. Malondialdehyde, β-carotene, copper, zinc and interleukin-6 in FF differed significantly between the group with COS and the group from mNC. Successful fertilization is linked by higher concentrations of vitamin A, copper and zinc and interleukin-6. The pregnant group have increased copper concentrations in FF. Ovarian stimulation using a GnRH antagonist protocol may induce oxidative stress and inflammatory changes in FF, associated with increased antioxidant demand and microelements concentrations. Successful fertilization is linked with antioxidant response marked by higher concentrations of vitamin A, and copper and zinc. Increased IL-6 concentrations may indicate a favorable inflammatory and oxidative environment supporting fertilization. Increased copper concentrations in the pregnant group can be potential factor but it requires further investigation.
CITED2 is a transcriptional co-activator with widespread roles in development. We recently found that the nitrofen rat model of congenital diaphragmatic hernia (CDH) showed CITED2 dysregulation at a late stage of abnormal lung development, but the role of CITED2 in lung development remains unexplored. Here, we study potential pathways of CITED2 in multiple models of lung hypoplasia. We used CRISPR/Cas9-generated CITED2-deficient rats to examine fetal lung growth, lung morphometry and inflammatory gene expression. CITED2 and its potential up- and downstream mediators were also assessed in human CDH lungs, nitrofen-induced CDH rats, and miR-200b knockout mice. CITED2-deficient rats had signs of lung hypoplasia (reduced lung weights and smaller alveoli) but macroscopically intact diaphragms. Lung tissues from human CDH patients showed upregulated CITED2 abundance and chromosomal alterations at its locus. We identified miR-200b as a regulator of CITED2, with miR-200b knockout mice demonstrating increased Cited2 expression. We also identified SoxC family transcription factors as potential downstream mediators of CITED2's effect on lung development, with Sox4, Sox11, and Sox12 downregulated in a rat nitrofen model of CDH, but Sox4 and Sox11 upregulated in CITED2-deficient rats. CITED2 deficiency further led to increased pulmonary Nfκb and decreased Il1β expression. Our data suggest that CITED2 is crucial for fetal lung development, alveolar structure and balanced inflammatory signaling. Both under- (Cited2-/-) and overexpression (CDH) of CITED2 result in lung hypoplasia. SoxC family transcription factors were dysregulated in both models of abnormal lung development, which may be related to downstream changes in inflammatory cytokine expression. Evidence supports miR-200b as an upstream regulator of CITED2, which can be targeted in future studies of abnormal lung development and CDH.
Limited data is available for long-term outcomes after percutaneous coronary intervention (PCI) of coronary drug-eluting stent (DES) in-stent restenosis (ISR) in diabetics. Thus, the aim of this observational, retrospective study was to close this lack of evidence. Between January 2007 and February 2021, a total of 3511 patients with 5497 ISR lesions were treated at two large-volume centers in Munich, Germany, of which 1242 (35.4%) were diabetics. Endpoints of interest were the rates of cardiac death, repeat revascularization, and myocardial infarction (MI). Survival was analyzed using the Kaplan-Meier method. Differences between the groups were tested with the log-rank test. Conventional multivariable analysis with adjustment for relevant variables was performed. After 10 years, the rates of cardiac death were 42.8% for diabetics and 32.8% for nondiabetics (HRadj 1.55 [95% CI, 1.31-1.81], p < 0.001). MI occurred in 15.9% of diabetics and in 9.7% of non-diabetics (HRadj 1.70 [95% CI, 1.36-2.11], p < 0.001). The rates of repeat revascularization of target lesion (HRadj 1.17 [95% CI, 1.02-1.34], p = 0.028), target vessel, and nontarget vessel were significantly higher in diabetics as compared to nondiabetics. No statistically relevant difference was found regarding the rate of stent thrombosis. Compared to non-insulin-dependent diabetics, insulin-dependent diabetics show higher rates of cardiac death and MI, but comparable revascularization rates in both diabetic groups. In the long term, the rates of cardiac death, MI, and repeat revascularization after PCI of DES-ISR are significantly higher in diabetics, particularly in insulin-dependent diabetics, than in nondiabetics.
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Placenta enriched 1 (PLAC1) is a conserved X chromosome-linked gene expressed in the mammalian placenta. We investigated the biology of PLAC1 in the rat and human placenta. Plac1 transcripts were expressed in the junctional zone of the rat placenta and in intrauterine invasive trophoblast cells. Genome-edited Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, a deficiency of intrauterine invasive trophoblast cells, and a late-gestation-stage uterine-placental interface infiltrated with natural killer cells. PLAC1 facilitated rat trophoblast cell differentiation. In contrast, PLAC1 showed minimal contributions to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Furthermore, the impact of PLAC1 on cellular function is linked to furin (paired basic amino acid cleaving enzyme) in rat and human trophoblast cells. Thus, PLAC1 plays an important role in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.
High-intensity 5 km running offers an ideal framework to analyze the organism's multidimensional responses. Since previous research primarily analyzed isolated aspects of fatigue, this study aimed to examine the integrated acute neuromuscular, metabolic, and perceptual responses to a 5 km run. Twenty-one recreational male runners participated. Pre- and post-race assessments included body composition, blood lactate, m. rectus femoris ultrasound thickness, quadriceps maximal voluntary isometric contraction (MVIC), heart rate, perceived exertion (Borg CR10), and 5 km finish time. Statistical analysis was performed in the Jamovi software, utilizing descriptive statistics, the Shapiro-Wilk test of normality, the Wilcoxon signed-rank test with effect size calculation, and Spearman's correlation coefficient, at a significance level of p < 0.05. Post-race measurements revealed a significant decrease in quadriceps MVIC (pre: 305 ± 99 N vs. post: 259 ± 88 N; p = 0.002) and an increase in blood lactate (pre: 0.8 ± 0.4 vs. post: 6.9 ± 1.4 mmol/L; p < 0.001), alongside high average heart rates (165 ± 16 bpm). However, ultrasound-assessed muscle architecture remained unchanged. The 5 km run induced pronounced neuromuscular and metabolic fatigue. Unchanged muscle architecture suggests that acute strength decline is primarily mediated by metabolic and neural mechanisms, rather than immediate structural-morphological factors. These findings highlight the value of an integrated assessment approach for understanding acute fatigue responses following high-intensity 5 km running and may contribute to more precise training-load prescription and recovery monitoring in recreational runners.
Sentinel lymph node biopsy is the gold standard for axillary staging in early breast cancer. The conventional dual-tracer technique using technetium-99m (Tc-99m) and blue dye is highly effective but limited by radiation exposure and logistical complexity. Indocyanine green (ICG) fluorescence imaging offers a radiation-free, real-time alternative. This study aimed to assess the diagnostic performance and clinical feasibility of ICG-guided SLNB compared with the standard Tc-99m-nanocolloid method. This prospective, open label, single center paired diagnostic comparison trial was conducted at the Department of Surgery, University of Debrecen Clinical Centre, Hungary. Eligible patients had biopsy-confirmed ductal carcinoma in situ or clinically node-negative invasive breast cancer (T1-T3) undergoing breast-conserving surgery or mastectomy. Periareolar injections of 99mTc-nanocolloid and 5 mg ICG were performed according to standardized international SLNB protocols. Lymphatic mapping was achieved with gamma-radiation detecting and near-infrared fluorescence imaging. Sentinel node detection rate, number of retrieved nodes, metastatic involvement, and adverse events were recorded and analyzed. A total of 106 patients were included. ICG fluorescence achieved a sentinel node detection rate of 90,6%, compared with 97,1% for Tc-99m. A median of 2,1 lymph nodes were excised per patient. 21.7% received neoadjuvant systemic therapy and 63.2% had breast conserving surgery. The overall per-patient sentinel lymph node (SLN) detection rate was 90.6% with indocyanine green (ICG), 97.1% with technetium-99m (Tc-99m), and 98.1% with the combined technique. On a per-node basis (n = 221), detection rates were 88.2%, 83.7%, and 100%, respectively. Among patients with positive SLNs (n = 34), metastatic node detection was 94.1% using ICG, 79.4% with Tc-99m, and 100% with the combined approach. In both upfront surgery and neoadjuvant subgroups, no statistically significant differences were observed between detection methods (p > 0.05); however, interpretation of neoadjuvant results was limited by the small sample size. No ICG-related complications or adverse events were reported. ICG fluorescence-guided SLNB alone is a safe, effective, and radiation-free alternative to conventional radioisotope mapping. Its high detection accuracy, simplicity, and real-time visualization support its integration into standard breast cancer surgery protocols. Further multicenter studies are warranted to validate long-term oncological outcomes.