Search Results (1,452)

Background and Objectives: Evidence on the acute effects of caffeine in female team-sport athletes is limited. This study aimed to quantify the acute effects of caffeine on female team-sport athletes across physical performance, sport-specific performance, physiological responses, perceptual responses, and cognitive performance and determine moderators. Methods: PubMed and Web of Science were systematically searched for randomized, placebo-controlled crossover trials of acute, dose-defined caffeine in female team-sport athletes. Effect sizes were expressed as Hedges’ g and synthesized within each domain using a three-level CHE model with CR2 cluster-robust variance estimation and Satterthwaite degrees of freedom; 95% confidence intervals and prediction intervals were reported. Risk of bias (RoB 2), methodological quality (PEDro), and certainty of evidence (GRADE) were assessed. Results: Twenty-six studies were included, comprising 26 randomized, blind, placebo-controlled crossover trials. As a descriptive cross-domain summary, acute caffeine intake showed a small overall effect when all available domains were pooled (Hedges’ g = 0.24, 95% CI 0.13 to 0.35); however, because these domains represent different constructs, domain-specific estimates were considered the primary interpretable findings. For physical performance, caffeine showed a small favorable effect (g = 0.32, 95% CI 0.22 to 0.42), with statistical evidence for repeated sprint ability (g = 0.43), agility or change in direction (g = 0.42), sprint or speed performance (g = 0.39), anaerobic power (g = 0.30), and jumping performance (g = 0.29). For sport-specific performance, the pooled estimate indicated a small favorable effect but did not reach conventional statistical significance (g = 0.36, 95% CI: −0.01 to 0.73). Exploratory sub-indicator analyses, each based on only a few studies, suggested possible favorable directions for sport-specific locomotion or running performance (g = 0.46) and throwing or ball-speed outcomes (g = 0.19), whereas evidence was insufficient for shooting or scoring accuracy. Physiological outcomes were direction-aligned to the value conventionally regarded as favourable for each indicator (i.e., lower heart rate, lactate, and glucose), so that positive values denote the conventionally favourable direction; because the domain aggregates indicators of differing clinical desirability, its pooled value is a descriptive summary only and showed no clear domain-level direction (g = −0.05, 95% CI −0.31 to 0.21). The heart rate submetric showed a statistically detectable difference (g = −0.30), indicating that caffeine increased heart rate, the expected pharmacological response to a stimulant rather than an adverse effect; there were no clear effects on blood lactate or blood glucose. Perceptual responses improved modestly (g = 0.42), largely through reduced rating of perceived exertion (g = 0.35). Cognitive performance, based on only four studies with low degrees of freedom and wide uncertainty, showed a nonsignificant direction (g = 0.37) with no clear evidence for reaction time or cognitive accuracy, and these data should not be interpreted as showing that caffeine improves cognitive performance in female team-sport athletes. Exploratory moderator analyses did not provide statistically reliable evidence of moderation by caffeine dose, timing of intake, formulation or source, sport type, competitive level, habitual caffeine intake, or blinding status. Conclusions: Available evidence most consistently supports small, outcome-specific benefits of acute caffeine for physical performance and reduced perceived exertion. Evidence for sport-specific skills and cognitive outcomes remained uncertain, based on few studies per outcome and not supporting a general benefit. Current data do not support dose-, timing-, formulation-, habitual-intake-, sport-, or population-stratified recommendations. Future trials should be adequately powered, prospectively report menstrual-cycle phase, hormonal-contraceptive use, habitual caffeine intake, and adverse symptoms, and verify the integrity of blinding. Full article

Dairy cattle are particularly susceptible to welfare challenges that can negatively impact their behaviour, physiological responses, milk yield, and overall health. These challenges include rough handling by unfamiliar people, extreme climatic conditions, inconsistent feeding, regrouping, and transportation. This pilot study investigated the interrelationships between behavioural and physiological responses and milk production of dairy cows reared in a smallholder stall housing system, restricting cow movement to standing and lying down in the Rajshahi district of Bangladesh. Fifty cows were observed, with all cows assessed over two days. Video recordings were made using a smartphone during the morning milking routine, focusing on specific behaviours: ear position (upright, forward, backward, downward), sniffing, stepping, and tail movement. Observations were conducted during the first two minutes after the start of the milking process manually. Physiological responses recorded included rectal temperature, vaginal temperature, and heart rate. Productivity outcomes include body condition score (BCS), milk yield per milking, daily milk yield, and milking frequency. Environmental data were collected to calculate the Temperature-Humidity Index (THI), which averaged 84.5 (±1.78 SD), exceeding the thermal comfort zone for dairy cattle (THI < 72). Statistical analyses comprised principal component analysis (PCA) to determine the most descriptive variables. Pearson correlation assesses the direction and strength of relationships between variables, and simple linear regression to evaluate milk production variables using all other variables as predictors. Results showed that cows displaying an upright ear position during milking had a positive relation with average daily milk yields (r = 0.456, p = 0.001). Milk yield was negatively correlated with THI (r = −0.331, p = 0.02), forward ear position (r = −0.356, p = 0.01), kicking (r = −0.531, p < 0.001), and sniffing behaviour during milking (r = −0.511, p < 0.001). The daily milk yields were positively correlated with body condition scores of milking cows (r = 0.661, p < 0.001). Rectal and vaginal temperatures were positively associated with each other (r = 0.777, p < 0.001). Similarly, rectal temperature and heart rate were positively associated with each other (r = 0.511, p < 0.001). Therefore, ear position, kicking, and sniffing behaviour during milking were used to assess emotional states, with forward ears associated with signs of stress. Healthy cows with higher body condition scores (BCS) produced more milk, requiring farmers to milk them more than twice a day. This pilot study highlights key behaviour and physiological responses relevant to stress and milk production, and thus overall welfare. For greater generalisability, future research should incorporate larger sample sizes and repeated environmental assessments over extended periods. Full article

Background/Objectives: Exogenous ketone supplementation has been proposed to enhance endurance performance by altering substrate metabolism and sparing muscle glycogen. Prolonged carbohydrate restriction may upregulate ketolytic capacity and could therefore modulate the response to exogenous ketone ingestion. This study investigated the impact of increasing circulating ketone bodies through exogenous ketone supplementation on endurance performance in athletes chronically adapted to a ketogenic diet. Methods: Participants (n = 9 recreationally active males, with ≥1 year of ketogenic adherence) visited the lab four times. The first visit determined their $\stackrel{.}{\mathrm{V}}$O₂max. The second visit accustomed them to test procedures. In a counterbalanced design, visits three and four tested the consumption of a 60 g carbohydrate beverage (CHO), or a beverage comprising 60 g carbohydrate and 0.5 g/kg 1,3-butanediol (CHO + BD). This was followed by a 60 min set-intensity exercise bout, followed by a 16.1 km time trial. Results: βHB significantly increased in the CHO + BD group (rest: 0.72 ± 0.33 mmol/L; post-exercise: 1.69 ± 0.30 mmol/L) compared to CHO (rest: 0.80 ± 0.53; post-exercise: 0.55 ± 0.30) (p < 0.001). There was no significant difference in time trial performance between groups (1606 ± 138 s; 1620 ± 134 s; p > 0.05). During set intensity exercise, there was no significant main effect of supplementation on lactate concentration, substrate oxidation, oxygen consumption at a fixed workload, RPE or heart rate (p > 0.05). However, glucose was significantly lower at minutes 40 and 60 of set intensity exercise in CHO + BD compared to CHO. Conclusions: No significant effect of 1,3-butanediol ingestion on endurance performance was detected in this sample of nine chronically ketogenic male athletes. βHB significantly increased from resting levels; however, time trial performance did not differ between conditions. Given the small sample and limited statistical power, these preliminary findings indicate no detectable ergogenic effect under the present conditions rather than evidence of no effect, and larger studies are warranted. Full article

Background/Objectives: About one-third of patients who receive cardiac resynchronization therapy (CRT) do not show meaningful clinical improvement. One possible reason is that current criteria for diagnosing left bundle branch block (LBBB) do not clearly separate true conduction block from other conditions that can produce a similar QRS pattern, since they rely mainly on surface ECG features. The Strauss criteria have been proposed as a stricter alternative. They include sex-specific QRS duration thresholds and require a mid-QRS notch or slur, with the goal of better identifying patients whose conduction abnormality may be correctable. Selecting candidates on this basis reflects a personalized-medicine approach that matches resynchronization to the individual conduction substrate rather than applying a single wide-QRS threshold to all patients. In this review, we assess whether LBBB defined by the Strauss criteria is linked to better CRT outcomes, and we examine how these criteria have been used in the design of randomized clinical trials investigating conduction system pacing (CSP). Methods: A systematic search of PubMed, EMBASE, and the Cochrane Library was conducted (last updated April 2026) in accordance with PRISMA 2020 guidelines. Evidence was drawn from two groups of studies: (1) observational studies comparing CRT outcomes in Strauss-positive versus Strauss-negative patients, and (2) randomized CSP trials conducted in populations enriched using either Strauss-type or typical LBBB morphology. Results: A total of 17 comparative studies (n ≈ 4200) were included in Part 1; most (14 of 17) reported outcomes favouring Strauss-defined LBBB, with the greatest signal in non-ischemic cardiomyopathy, although these were mostly small retrospective studies with heterogeneous outcome definitions. However, two large registry analyses found no incremental benefit of strict over conventional criteria. In Part 2, six randomized controlled trials were analyzed. The HeartSync-LBBP trial (n = 200, 36-month follow-up) demonstrated significantly lower rates of mortality or heart failure hospitalization with LBBP compared to BiVP (8% vs. 28%; HR 0.26; 95% CI 0.12–0.57), with 98% technical success for LBBP. In contrast, the PhysioSync-HF trial (n = 173) showed superiority of BiVP, with CSP success of only 69% and 42.8% of procedures performed by less experienced operators. Similarly, the LEFT-BUNDLE-CRT trial (n = 176) found that LBBAP did not meet non-inferiority criteria compared to BiVP (RR 0.95; 95% CI 0.88–1.02). Conclusions: Strauss-defined LBBB is associated with improved CRT outcomes in observational studies, particularly in non-ischemic cardiomyopathy; this reflects an association rather than established superiority or causal benefit, and no randomized trial has yet compared Strauss-guided against guideline-based patient selection. In randomized CSP trials, both operator experience and patient selection appear to be critical determinants of success. BiVP remains effective even in patients meeting strict Strauss criteria. Further research is needed to determine whether the application of Strauss criteria improves outcomes beyond current guideline-based patient selection. Full article

Aim: This two-center retrospective observational study evaluated whether outpatient conscious sedation protocols based on titrated nitrous oxide/oxygen, midazolam, or their combination enabled complex dental and minor oral surgical procedures to be completed in uncooperative pediatric and special needs patients, without escalation to deep intravenous sedation or general anesthesia. Materials and Methods: Forty pediatric and special needs patients treated at the Conscious Sedation Units of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (Milan, Italy) and Policlinico of Bari (Bari, Italy) were included. Overall, 60 complex dental or minor oral surgical procedures were performed. Procedures were classified according to the sedation protocol administered: Protocol A, nitrous oxide/oxygen inhalation sedation alone; Protocol B, midazolam alone; and Protocol C, combined midazolam and nitrous oxide/oxygen sedation. Vital signs were monitored before, during, and after treatment. The primary outcome was successful procedural completion, defined as completion of the planned procedure without premature termination, escalation to deep intravenous sedation or general anesthesia, or the need for unplanned airway or emergency medical intervention. Results: Forty patients underwent 60 procedures. The mean age was 8.7 ± 2.3 years (range, 4–14 years). Protocol A was used in 24 procedures (40%), Protocol B in 6 procedures (10%), and Protocol C in 30 procedures (50%). All procedures were completed successfully, with no conversion to general anesthesia, no airway crises, and no medical emergencies. Transient elevations in heart rate and blood pressure during local anesthesia occurred in 11/60 procedures (18.3%), and mild self-limiting nausea or fatigue occurred in 5/60 procedures (8.3%). Conclusions: The evaluated protocols were associated with successful procedural completion and few recorded adverse events in this selected cohort. Combined behavioral and pharmacological management was associated with completion of the planned procedures without conversion to deep intravenous sedation or general anesthesia. Comparative studies are required to determine whether these protocols reduce general-anesthesia utilization. Full article

Background: Exercise testing is routinely performed before initiation of phase II cardiac rehabilitation to assess exercise capacity and determine safe training intensity. However, exercise tests may be terminated before reaching the target heart rate due to various cardiovascular and non-cardiovascular factors. The aim of this study was to analyze the reasons for terminating exercise tests performed on a treadmill and a cycle ergometer, with particular emphasis on the impact of the patient’s clinical profile and exercise capacity. Methods: A retrospective analysis was conducted on 336 patients after myocardial infarction (74 women and 262 men) referred to inpatient phase II cardiac rehabilitation between 2019 and 2022. Patients were divided into two matched groups according to the type of exercise test performed: treadmill and cycle ergometer. Reasons for test termination, exercise performance parameters, and demographic and clinical characteristics were analyzed. Results: The most common reasons for exercise test termination were fatigue (55.1%) and achievement of the target heart rate (37.2%), with no significant differences between testing modalities. Lower limb pain was significantly more frequent during cycle ergometer testing compared with treadmill testing (16.1% vs. 7.1%; p = 0.011). Patients tested on the treadmill achieved significantly higher exercise capacity (7.19 vs. 5.28 METs (metabolic equivalents); p < 0.001), higher peak heart rate, and higher rate-pressure product. Multiple regression analysis showed that the association between exercise modality and lower limb pain was not independent after adjustment for clinical and demographic variables, indicating that the observed differences were largely explained by patient clinical characteristics. Conclusions: The most common reasons for exercise test termination were patient fatigue and attainment of the target heart rate, confirming the safety of submaximal exercise testing in post-myocardial infarction patients. Lower limb pain was more frequently observed during cycle ergometer testing in unadjusted analysis; however, this association was not independent of clinical variables, indicating that it is primarily related to the patient’s clinical profile rather than the exercise modality. Exercise testing should therefore be individualized according to clinical status, functional capacity, and rehabilitation goals. Full article

Background: Cardiotocography (CTG) represents a cornerstone in modern intrapartum fetal surveillance, allowing continuous assessment of fetal well-being through the analysis of fetal heart rate patterns in relation to uterine contractions. Despite its widespread clinical use, the interpretation of CTG tracings remains complex and is often associated with high interobserver variability and limited specificity in predicting adverse outcomes. In recent years, increasing attention has been directed toward placental pathology as a key determinant in the pathophysiology of adverse perinatal events. The placenta, as a dynamic organ mediating maternal–fetal exchange, plays a crucial role in fetal oxygenation and nutrient supply. Alterations in its structure and function may contribute to both chronic and acute fetal compromise. This retrospective study aimed to investigate the relationship between pathological intrapartum CTG tracings and maternal–fetal outcomes, with a particular focus on correlating these findings with macroscopic and microscopic placental abnormalities, compared to a control group of uncomplicated pregnancies with normal CTG patterns. Material and methods: We evaluated maternal, fetal, and placental histopathological data from 85 patients who exhibited pathological intrapartum cardiotocographic tracings. All deliveries occurred between January 2023 and March 2025 at the Obstetrics and Gynecology Departments of the ‘A. Gemelli’ University Hospital and Careggi University Hospital. A control group consisting of 50 women with normal CTG patterns and uncomplicated term singleton pregnancies, delivered at the same institutions, was used for comparison. Results: Cases with pathological CTG showed poorer neonatal outcomes compared with those with normal CTG. Infants in the pathological CTG group had lower Apgar scores, more frequent NICU admissions, and one case of hypoxic–ischemic encephalopathy. Mode of delivery, Apgar scores, NICU admission, and arterial pH were all significantly associated with CTG classification. A higher birth weight-to-placental weight ratio in the pathological CTG group suggested possible uteroplacental insufficiency. Macroscopic and histological placental findings, including hypercoiled umbilical cords and intervillous thrombosis, were also significantly more frequent in cases with pathological CTG. Conclusions: The findings of this study suggest that pathological CTG reflects not an isolated event but rather a multifactorial dysfunction of the feto-placental unit. Its associations with low Apgar scores, reduced arterial pH, abnormal BW/PW ratio, intervillous thrombi, and umbilical cord hypercoiling are consistent with existing evidence and support the interplay of chronic placental abnormalities and acute mechanical factors in the development of suspected fetal hypoxia. The future development of multivariate predictive models integrating clinical, biochemical, and anatomo-pathological variables may improve the early identification of pregnancies at risk and optimize intrapartum management, thereby reducing adverse perinatal outcomes. Full article

Background: The 6 min walk test (6MWT) is the gold standard for field-based functional assessment, yet the 3 min walk test (3MWT) offers a time-efficient alternative. However, a lack of localised normative reference values (NRV) and an over-reliance on simple 6 min extrapolation limit its clinical utility. Objectives: To establish the NRV and reference equations for the 3MWT in a healthy cohort and investigate the physiological relationship between 3 min performance and 6 min predictions. Methods: This cross-sectional study recruited healthy community-dwelling adults (aged 20 to 80, BMI < 27.5 kg/m²). Participants performed two 3MWT trials on a 30 m indoor course. Primary outcomes included the best 3MWT and physiological parameters. Reference equations were derived using multiple linear regression. Results: In total, 240 participants were recruited with an overall median 3MWT of 290 metres (m) (IQR 257.0–323.0). Males walked significantly farther than females (p = 0.002). While 3MWT remained stable across age decades in males (p = 0.225), females’ performance declined with age (p = 0.005). Older adults maintained walking distances comparable to younger cohorts by operating at a higher relative percentage of their predicted maximum heart rate and exhibiting prolonged recovery profiles. Doubling the 3MWT significantly overestimated 6 min capacity (p < 0.001), highlighting non-linear pacing strategies. Conclusions: This study provides the first age- and gender-specific NRV for the 3MWT in Singapore, supporting its use as a rapid functional walking assessment tool in healthy adults. The findings suggest that the 3MWT should not be interpreted as a direct linear surrogate for the 6MWT. Further research is required to validate these reference equations externally and determine their clinical sensitivity in disease populations. Full article

Introduction: Schizotypal traits (unusual perceptual experiences and cognitive-perceptual differences) and cyclothymic traits (mood instability and affective fluctuations) represent subclinical personality dimensions observed in non-clinical populations. Allostatic load (AL), reflecting cumulative multisystem physiological stress, may provide insight into biological processes associated with these traits. This study examined whether individuals with elevated schizotypy or cyclothymic traits show distinct AL-related biomarker patterns. Methods: Three groups were defined using validated psychometric measures: 30 individuals with schizotypy traits (PSF), 25 with cyclothymic traits (CF), and 30 control participants (CGs). Machine learning (ML) analyses included a Random Forest model with leave-one-subject-out cross-validation to examine differences in biomarker profiles between groups, and Shapley Additive exPlanations (SHAP) analysis was applied to determine the relative importance of biomarkers. The highest-ranking biomarkers were subsequently used to construct a reduced AL index. Results: Significant differences among groups were observed in oxidative stress system markers (p = 0.014). SHAP analysis identified creatinine, diastolic blood pressure, uric acid, and low-density lipids as key features for the CF group, and heart rate, TSH, uric acid, and glucose for the PSF group, with uric acid emerging as the strongest shared biomarker. A reduced biomarker panel selected using SHAP achieved subject-level classification accuracy of 63.6% (95% CI 50.9–76.4) and AUC of 0.625 (95% CI 0.469–0.768) and showed comparable performance to the full model. However, label-permutation testing yielded a borderline result (p = 0.055), indicating that these findings should be considered exploratory. The AL index derived from the top-ranked biomarkers was significantly lower in the CF than in the CG group (p = 0.007), whereas differences between the PSF and CG groups did not remain significant after correction. Findings are exploratory and require validation in an independent cohort. Conclusions: Distinct biomarker patterns associated with schizotypal and cyclothymic traits were identified in a non-clinical population, highlighting differences in stress-related physiological processes. ML-based feature-importance analysis identified a reduced set of biomarkers associated with trait-related biological profiles; however, these findings remain exploratory and require external validation. Full article

Background: Optimising medication for Attention Deficit Hyperactivity Disorder (ADHD) is often hindered by the lack of practical physiological indicators that can inform treatment effects. Electrooculography (EOG) has been suggested as a low-burden marker of neurophysiological processes relevant to ADHD, but its responsiveness to medication within routine clinical settings is not well established. Methods: We analysed anonymised clinical records from adults with ADHD receiving stable, ongoing medication who underwent closed-eye EOG recordings immediately before and after taking their scheduled dose during standard consultations. Recordings were obtained using clinical EEG equipment. Heart rate and blood pressure, measured after each EOG session, were included as contextual indices of physiological state. Pre–post changes were assessed using paired t-tests and binomial tests, with effect sizes and confidence intervals reported for the main pre–post comparisons, with Pearson correlations used to evaluate associations between EOG and cardiovascular measures. Results: Both mean and peak EOG power showed consistent within-session reductions, with the majority of individuals exhibiting a decrease across measures. Cardiovascular parameters showed no systematic pre–post change, and differences in cardiovascular measures did not correlate with changes in EOG activity. Conclusions: Closed-eye EOG showed systematic within-session modulation in adults with ADHD on stable treatment. These preliminary findings suggest that EOG is sensitive to short-latency physiological changes occurring within a clinical timeframe. However, the present design does not establish pharmacological specificity, and further controlled studies are needed to determine whether such changes are specifically medication related and whether they have relevance for treatment monitoring and titration. Full article

This study evaluated the reliability of five treadmill protocols that assess heart rate (HR) and blood lactate (Bla) responses in Thoroughbred horses to determine their effectiveness in serving as potential tools for monitoring fitness and the wellbeing of racehorses. Of the five exercise tests, four consisted of repeated interval gallops at constant speeds (8 m/s and 10 m/s) and grade (6°) and one test of a continuous gallop at constant speeds (8 m/s) and grade (6°). Eight hundred and twenty-three gallops in total were performed by 64 horses. The test–retest reliability and absolute agreement between treadmill tests were assessed using Intraclass correlation coefficient (ICC) with a two-way mixed-effect model. Statistical significance was set at p < 0.05. Overall, the mean of the mean HR for each of the five test gallops was 203 ± 11.3 bpm. The mean HR ICC of the five tests of 0.756 indicates good reliability of the tests, as HRs during each gallop were consistent between tests. Protocol comparison showed that all protocols have good reliability with gallops 1 and 5 scoring highest (0.79: 0.81) and gallop 4 lowest at 0.621. The recovery mean HR ICC for 30 s, 60 s, 90 s and 120 s recovery were 0.421, 0.504, 0.595 and 0.571 respectively. Overall, the data suggests that gallop HR is the more reliable variable with recovery HRR reliability improving to an acceptable level at 60 s and 90 s recovery. Together, the treadmill tests demonstrated acceptable reliability to measure both gallop HR and HHR responses, whereas BLa responses were less consistent. Full article

The assessment of consciousness has been shaped largely by research on acquired disorders of consciousness after acute or chronic brain injury, but similar problems of unreliable behavioral expression increasingly arise in neurodegenerative disease. This translational overlap is especially relevant when preserved cognition, awareness, or intentionality cannot be reliably expressed because of severe motor impairment, fluctuating arousal, cognitive decline, aphasia, apraxia, or impaired cooperation. In neurodegenerative disease, degeneration of arousal systems, large-scale brain networks, cognition, and motor pathways may similarly make observable behavior an unreliable measure of awareness. The challenge is not only to determine if a patient responds, but also to ask if residual awareness, intentionality, or covert cognition can still be detected through physiological signals. This review discusses how contemporary modalities reshape this assessment. Electroencephalography has moved from a descriptive measure of background activity to a bedside tool capable of probing event-related responses, network organization, and cortical complexity. Magnetic resonance methods reveal altered connectivity within thalamocortical and default mode network systems, while functional near-infrared spectroscopy adds a portable hemodynamic approach that may be repeated at the bedside and integrated with active paradigms. Brain–computer interfaces provide a translational step by converting neural responses into evidence of command following or, in selected patients, into communication, and artificial intelligence strengthens these approaches by extracting clinically meaningful patterns from complex neural and hemodynamic data. Additionally, autonomic measures, including heart rate variability and baroreflex indices, are considered as auxiliary physiological context for arousal and engagement, and not as direct markers of awareness. Because the most mature evidence for covert awareness and cognitive-motor dissociation comes from acquired disorders of consciousness, this review treats brain injury literature as a methodological foundation instead of as directly interchangeable evidence for neurodegenerative disease. It then examines how these approaches may be adapted to neurodegenerative contexts, especially ALS, severe dementia, Lewy body disease with fluctuating cognition, and conditions in which communication or motor output becomes unreliable. Full article

Chronic kidney disease, acute kidney injury and cardiorenal syndrome are major determinants of cardiovascular morbidity and mortality, yet conventional renal assessment based on serum creatinine, estimated glomerular filtration rate and urine output often fails to detect early structural injury or pathway-specific cardiorenal risk. This narrative review synthesized recent evidence on emerging renal and cardiorenal biomarkers with potential value for cardiovascular risk stratification beyond creatinine. Literature published between 2015 and April 2026 was reviewed, focusing on biomarkers of tubular injury, functional renal impairment, fibrosis/remodeling and mineral metabolism. NGAL and KIM-1 may detect tubular stress and proximal tubular injury before overt functional decline and have shown relevance in heart failure, acute coronary syndromes and post-cardiac surgery settings. Cystatin C and pro-enkephalin refine functional renal assessment and may improve prognostic classification when creatinine is confounded by frailty, muscle mass or acute hemodynamic changes. Soluble ST2 and galectin-3 reflect inflammation, fibrosis and cardiorenal remodeling, while FGF-23 links kidney dysfunction to cardiovascular risk through phosphate imbalance, vascular calcification and myocardial hypertrophy. Multi-biomarker panels may help identify dominant cardiorenal phenotypes and personalize monitoring intensity. However, routine implementation requires standardized assays, validated thresholds, cost-effectiveness data and prospective evidence that biomarker-guided management improves clinical outcomes. Full article

Background: Malnutrition is increasingly recognized as an important determinant of prognosis in patients with heart failure (HF). The Geriatric Nutritional Risk Index (GNRI) is a simple nutritional assessment tool associated with adverse cardiovascular outcomes, but its relationship with diabetes mellitus and in-hospital mortality in hospitalized HF patients remains incompletely characterized. This study evaluated the association between GNRI-defined nutritional risk, diabetes mellitus, and in-hospital mortality in patients hospitalized with HF. Methods: This prospective observational study included 278 consecutive patients hospitalized with HF at a tertiary cardiology center between September 2025 and March 2026. Nutritional status was assessed using GNRI, and patients were classified as having no nutritional risk (GNRI ≥ 98) or GNRI-defined nutritional risk (GNRI < 98). Logistic regression evaluated the association between GNRI and diabetes mellitus, while Cox proportional hazards regression and Kaplan–Meier analyses assessed in-hospital mortality. Results: GNRI-defined nutritional risk was identified in 42.1% of patients. Compared with patients without nutritional risk, those with GNRI-defined nutritional risk had a higher prevalence of diabetes mellitus (73.5% vs. 50.9%, p < 0.001), longer hospital stays, and a nearly threefold higher in-hospital mortality rate (29.1% vs. 10.6%, p < 0.001). Higher GNRI values were associated with a lower prevalence of diabetes mellitus. Lower GNRI values were also associated with higher in-hospital mortality in the main Cox models; however, this association was attenuated and no longer statistically significant after adjustment for markers of heart failure severity. Conclusions: Lower GNRI values identified patients with greater nutritional and clinical vulnerability during hospitalization for HF. Further studies are needed to determine whether GNRI provides incremental prognostic value beyond established HF risk markers. Full article

Objective. This study performed a comparative analysis of autonomic responses during voluntary breath-holds at inspiration and expiration by assessing low-frequency (LF) oscillations in heart rate (HR) and photoplethysmogram (PPG) signals. Methods. Eleven healthy volunteers underwent a modified head-up tilt test with breath-holds at inspiration and expiration in supine and standing positions. Electrocardiogram, finger PPG, and respiratory signals were recorded simultaneously. LF oscillation (0.04–0.15 Hz) amplitudes were assessed during spontaneous breathing and breath-hold phases. Relative changes in LF amplitudes (ΔLFA) were calculated for each signal, and the ΔLFA ratio (ΔLFA_PPG/ΔLFA_HR) was derived. Results. Cardiac and vascular signals showed divergent responses in LF oscillation amplitude during breath-holds. While PPG signals demonstrated a significant increase during expiration-holds (ΔLFA_PPG = +71.56%, p = 0.003), HR signals showed a non-significant overall decrease (ΔLFA_HR = −25.28%, p = 0.481). In this exploratory study (n = 11), comparative analysis showed that the vascular response (ΔLFA_PPG) was significantly greater than the cardiac response (ΔLFA_HR) during expiration-holds (p = 0.005) and across all stages (p = 0.012). However, expiration holds were systematically shorter than inspiration holds by approximately 24 s (median 32.1 s vs. 56.3 s). Because breath-hold duration was self-determined and not standardized, the observed differences between inspiration and expiration conditions may reflect either respiratory phase, cumulative apnea duration, or their interaction (our design cannot disentangle these effects). The ΔLFA ratio showed a negative median value overall (−0.25), indicating a complex and often inverse relationship between vascular and cardiac responses. However, due to the small sample size (n = 11), these results are strictly hypothesis-generating and cannot be generalized beyond the studied cohort. The study was powered only to detect large effect sizes (Cohen’s d > 1.2), and the wide bootstrap confidence intervals indicate substantial estimation uncertainty. Independent replication in larger, more diverse populations is essential before any clinical or physiological generalization can be made. Conclusions. This study documents opposing directional changes in cardiac and peripheral vascular LF oscillations during shorter expiration and longer inspiration breath-hold. Because respiratory phase and apnea duration are confounded in our design, we cannot determine whether these differential responses are phase-dependent, duration-dependent, or driven by both factors. The findings highlight the necessity of multi-signal analysis incorporating both ECG and PPG for a more comprehensive autonomic assessment of local and systemic autonomic influences and underscore that future studies must employ standardized breath-hold durations across both respiratory phases to isolate the specific contribution of respiratory phase. The ΔLFA ratio is explored here as a descriptive metric of the direction and magnitude of cardiac-vascular response differences, but its mathematical stability and physiological interpretation remain limited and require validation with direct sympathetic nerve recordings. Full article