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Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with fragile brain function during the non-acute phase undergoing laparoscopic colorectal surgery: A randomized controlled trial.

BACKGROUND AND PURPOSE: Older adults with non-acute fragile brain function (NFBF) may be particularly susceptible to perioperative disturbances in cerebral oxygenation and postoperative neurocognitive decline. Permissive hypercapnia (PHC) may enhance cerebral oxygenation, but its effects in this population remain unclear. We examined whether PHC-based ventilation improves intraoperative regional cerebral oxygen saturation (rSO2) and early postoperative cognitive outcomes in older patients with NFBF undergoing elective laparoscopic colorectal surgery. METHODS: In this single-center, single-blind randomized trial, 76 patients were assigned in a 1:1 ratio to PHC-based or conventional ventilation. The primary outcome was the absolute change in rSO2 from baseline (T0) to the end of surgery (T4). Analyses followed the intention-to-treat principle, with prespecified per-protocol sensitivity analysis. Secondary outcomes included intraoperative rSO2 trajectories, cerebral oxygen extraction-related indices, early postoperative cognitive screening, serum neuron-specific enolase and interleukin-6, and safety outcomes. RESULTS: PHC significantly increased rSO2 relative to conventional ventilation (left: adjusted mean difference [aMD] 10.64, 95% CI 8.96-12.33; right: aMD 10.16, 95% CI 8.22-12.11; both P&#xa0;<&#xa0;0.001), with consistent sensitivity results. Repeated-measures analyses showed persistently higher intraoperative rSO2 in the PHC group. Cerebral oxygen extraction-related indices were generally lower with PHC. However, early postoperative cognitive outcomes and serum biomarkers did not differ between groups. Emergence time was modestly longer with PHC, whereas adverse events were comparable. CONCLUSIONS: PHC-based ventilation favorably modified intraoperative cerebral oxygenation and oxygen-extraction profiles but did not translate into detectable early postoperative cognitive or biomarker benefits in older adults with NFBF.

Humans

Effectiveness of an AI-based home exercise app for rehabilitation of rotator cuff-related shoulder pain: A randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain contributes to disability and healthcare use. Although therapeutic exercise is first-line treatment, limited supervision and adherence may reduce its effectiveness; digital rehabilitation with real-time feedback may address these limitations. OBJECTIVES: To evaluate the effectiveness of adding a digital rehabilitation program to standard physiotherapy on pain, function, fear-avoidance beliefs, and healthcare utilization. DESIGN: Single-center, assessor-blinded, randomized controlled trial with two parallel groups. METHOD: Forty-six adults (mean age 59 years) with rotator cuff-related shoulder pain were randomized to 12 weeks of conventional physiotherapy or physiotherapy plus an AI-based digital rehabilitation program using computer vision for real-time feedback and performance monitoring. Outcomes were assessed at baseline and at 2, 4, and 12 weeks. Pain intensity (NPRS) was primary outcome; secondary outcomes included upper limb function (QuickDASH), fear-avoidance beliefs (FABQ), and post-intervention healthcare utilization. Analyses followed an intention-to-treat approach. RESULTS: Pain reduction exceeded the MCID (1.3) at 4 and 12 weeks. Between-group differences favoured the intervention at Weeks 2 and 4 (MD -0.7; 95% CI -1.13 to -0.14 and MD -1.01; 95% CI -1.8 to -0.2, respectively). Upper limb function improved more at Week 4 (MD -7.3; 95% CI -12.3 to -2.2). FABQ scores decreased more at Week 12 (MD -7.6; 95% CI -14 to -0.5). Fewer participants in the experimental group required post-intervention healthcare (3 vs 10; p&#x202f;=&#x202f;0.02). CONCLUSION: Adding AI-based home exercise app to conventional treatment improve pain and may improve function and reduce healthcare utilization in rotator cuff-related shoulder pain.

Humans

Effect of protective ventilation throughout the intubation period on perioperative oxygenation in patients undergoing MIDCABG: a randomised controlled trial.

INTRODUCTION: Minimally invasive direct coronary artery bypass grafting (MIDCABG) requires prolonged one-lung ventilation (OLV), increasing postoperative pulmonary complications (PPCs) risk. We investigated whether protective lung ventilation (PLV) throughout intubation benefits MIDCABG patients. METHODS: In this single-center randomized study, MIDCABG patients received PLV (low tidal volume of 6-8&#x2009;mL&#xb7;kg-1, PEEP of 6&#x2009;cm H2O, alveolar recruitment maneuvers) or conventional mechanical ventilation (CMV, tidal volume of 8-10&#x2009;mL&#xb7;kg-1, without PEEP or maneuvers) from tracheal intubation to extubation. The primary outcome was perioperative oxygenation, assessed by the PaO2/FiO2 ratio. RESULTS: Sixty patients (n = 30 per group) were enrolled. Compared with CMV, PLV improved PaO2/FiO2 ratios (mean difference at OLV60: 34.56&#x2009;mmHg; 95% CI: 11.78-57.33; p&#x2009;<&#x2009;0.01), shortened median durations of postoperative mechanical ventilation (median difference: -4.5&#x2009;h, 95% CI: -8.5 to -0.5; p&#x2009;=&#x2009;0.013) and hospital stay (median difference: -3.0&#x2009;days, 95% CI: -5.0 to -1.0; p&#x2009;=&#x2009;0.019). PLV also reduced driving pressure, airway pressure and intrapulmonary shunt during OLV (all p&#x2009;<&#x2009;0.05). Desaturation occurred in 23.3% of CMV patients and 13.3% of PLV patients (p&#x2009;=&#x2009;0.506). Hemodynamic parameters were generally comparable between groups, except for lower MPAP and PVRI in the PLV group during OLV and after ICU admission (p&#x2009;<&#x2009;0.05). The incidence of PPCs did not differ between groups. CONCLUSIONS: In patients undergoing MIDCABG, PLV applied throughout intubation improved perioperative oxygenation and shortened the duration of postoperative mechanical ventilation and hospital stay, but did not reduce PPCs. CLINICAL TRIAL REGISTRATION: ChiCTR1900022005.

Humans

Conduction System Pacing Versus Right Ventricular Pacing in Patients With Atrioventricular Block and Anticipated High Pacing Burden.

Right ventricular pacing (RVP) in patients with atrioventricular (AV) block and high anticipated pacing burden is associated with pacing-induced cardiomyopathy (PICM) in approximately 12% to 20% of patients, whereas conduction system pacing (CSP) preserves more physiologic ventricular activation and may mitigate these consequences; the totality of contemporary randomized evidence has not been systematically pooled. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing CSP with RVP in patients with AV block or anticipated high ventricular pacing burden and a minimum 6-month follow-up, with co-primary outcomes of PICM incidence and change in left ventricular ejection fraction (&#x394;LVEF) and secondary outcomes of heart failure hospitalization (HFH), all-cause mortality, composite clinical endpoint, and paced QRS duration (PROSPERO CRD420261400227); random-effects meta-analysis used DerSimonian-Laird estimation. Five RCTs (LBBP-FAVOUR, CSPACE, Prague CSP, PACE-HF, STAY; N = 806) met inclusion criteria. CSP significantly reduced PICM (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.18 to 0.48; p <0.001; I&#xb2; = 0%; k = 4), was associated with greater LVEF preservation (pooled mean difference [MD] +4.41%, 95% CI +1.82 to +6.99; p = 0.001; I&#xb2; = 87%; k = 5), and reduced HFH (HR 0.24, 95% CI 0.12 to 0.48; p <0.001; I&#xb2; = 0%; k = 5). CSP shortened paced QRS duration (MD -27.5 ms, 95% CI -32.6 to -22.5; p <0.001; k = 5). All-cause mortality was numerically lower with CSP but did not reach significance (HR 0.57, 95% CI 0.29 to 1.12; p = 0.10; k = 4). In a prespecified sensitivity analysis restricting to multicenter trials with N &#x2265; 150, all findings were concordant with the primary analysis. In conclusion, CSP substantially reduces PICM, preserves LVEF, and reduces HFH compared with RVP in patients with AV block and anticipated high pacing burden, supporting its consideration as the preferred pacing strategy in appropriately selected patients.

Humans

Machine learning vs. traditional methods for predicting postoperative cardiac complications after non-cardiac surgery: a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Accurate prediction of peri-operative cardiac complications is critical to optimise pre-operative decision-making. Traditional risk prediction scores, such as the Revised Cardiac Risk Index, show only modest discrimination. Machine learning can model complex, non-linear relationships but their predictive performance compared with traditional scores remains unclear. METHODS: We performed a systematic review and Bayesian network meta-analysis. The primary outcome was postoperative adverse cardiac events following non-cardiac surgery. Prediction models were assessed relative to the Revised Cardiac Risk Index. As many studies evaluated multiple versions of each model type, the highest performing ('best version') and lowest performing ('worst version') results were analysed. Models were ranked using the surface under the cumulative ranking curve (SUCRA). RESULTS: Thirteen studies evaluating 54 models and 927,113 patients were included. Machine learning approaches generally outperformed traditional risk scores. Automated machine learning ranked highest (SUCRA 96.6) showed the greatest improvement in the best version analysis (mean difference (MD) 0.28 (95%CrI 0.16-0.40)) and remained superior in the sensitivity analysis (MD 0.30 (95%CrI 0.14-0.45)). Gradient boosting models showed superior performance over the Revised Cardiac Risk Index across analysis (best version: MD 0.20 (95%CrI 0.14-0.26), worst version: MD 0.18 (95%CrI 0.12-0.25), SUCRA 82.4). The Gupta Perioperative Risk for Myocardial Infarction or Cardiac Arrest score outperformed the Revised Cardiac Risk Index in the best version analysis (MD 0.16 (95%CrI 0.01-0.32)). Between-study heterogeneity was low. None of the included studies externally validated their machine learning models and only six were judged to be at low risk of bias. DISCUSSION: Most machine learning models showed better discrimination than traditional risk scores, with automated machine learning and gradient boosting models ranking highest. However, study quality, calibration reporting and absence of external validation limit immediate clinical adoption. Prospective, multicentre evaluation is required before integration of these models into peri-operative practice.

Humans

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p&#xa0;<&#xa0;0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p&#xa0;=&#xa0;0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans

First evaluation of a novel recombinant eCG molecule in ewes reveals a discrepancy between ovulatory response and pregnancy outcome.

This study evaluated the reproductive performance and clinical safety of a novel recombinant eCG (r-eCG) in ewes. Two weeks prior to study onset (Day 0: intravaginal progesterone device insertion), 45 ewes were randomly assigned to negative control (NC; no eCG; n&#x202f;=&#x202f;10), positive control (PC; 400IU commercial non-recombinant eCG; n&#x202f;=&#x202f;20), or treatment group (T; 400IU r-eCG; n&#x202f;=&#x202f;15). Ewes were inseminated with fresh-diluted semen (200&#x202f;&#xd7;&#x202f;106 sperm). Ultrasonography assessed follicle count/diameter (days 11, 13), ovulation (day 13), corpus luteum (CL) number/characteristics (day 20), and pregnancy (day 44). Serum progesterone was measured on day 20; Group T underwent clinical/hematological evaluations (days 0, 20, and 44). Estrus signs were more frequent (P&#x202f;<&#x202f;0.01) in T (100%) than NC (50%), while PC (85%) did not differ. Ovulation rates were similar between T (93%) and PC (95%), but higher than NC (50%; P&#x202f;<&#x202f;0.05). On day 13, largest follicle diameter did not differ (P&#x202f;>&#x202f;0.05) among groups; however, fewer follicles > 2&#x202f;mm occurred in PC than NC and T (P&#x202f;<&#x202f;0.05). CL number was higher in T than PC (2.0&#x202f;&#xb1;&#x202f;0.3 vs. 1.0&#x202f;&#xb1;&#x202f;0.0, P&#x202f;<&#x202f;0.01), while NC did not differ (1.0&#x202f;&#xb1;&#x202f;0.25). Conversely, pregnancy rate was higher (P&#x202f;<&#x202f;0.05) in PC (70%) than T (28.6%) and NC (20%). Among ovulated ewes, progesterone concentration and progesterone/CL ratio did not differ among groups (P&#x202f;=&#x202f;0.92 and P&#x202f;=&#x202f;0.08, respectively). No relevant r-eCG-related clinical or hematological alterations occurred. In conclusion, 400IU r-eCG effectively induces estrus and ovulation without adverse effects; however, the discrepancy between ovulatory response and pregnancy rate underscores the need for further study refinement to improve fertility.

Animals

Alarms and alarm management with automated versus conventional ventilation in neurocritical care patients.

INTRODUCTION: False or clinically irrelevant alarms are a major driver of ICU alarm fatigue and nursing workload. Ventilator alarms make up a large share, and although automated ventilation modes can reduce manual adjustments, their effect on alarm burden is still unclear. This issue can be particularly relevant in neurocritical care patients, where precise ventilator and alarm management is imperative for patient safety. OBJECTIVES: This explorative post hoc analysis of a randomized clinical trial compared alarm frequency and management between automated ventilation and conventional ventilation in neurocritical care patients. METHODS: Ventilator alarms and manual ventilator changes were captured continuously from the ventilator for up to 24&#xa0;h per patient. The primary endpoint was a composite of workload-relevant alarms; with alarm management interventions at the ventilator as a key secondary outcome. Additional endpoints included redundant alarms, alarm duration and ventilator management. RESULTS: 13 patients received automated ventilation and 24 received conventional ventilation. No difference was observed in workload-relevant alarm frequency between automated and conventional ventilation (3.28 [2.87 to 4.30] vs 3.73 [1.66 to 7.33] alarms per hour; P&#xa0;=&#xa0;0.81), while alarm management interventions at the ventilator were lower with automated ventilation (0.14 [0.10 to 0.15] vs 0.21 [0.17 to 0.31] interventions per hour; P&#xa0;=&#xa0;0.01). Other alarm frequencies, duration of alarms and ventilator management were similar. CONCLUSIONS: In this exploratory post hoc analysis of a randomized clinical trial in neurocritical care patients during the early phase of mechanical ventilation, automated ventilation did not reduce the frequency of total or workload-relevant alarms, nor their duration, but was associated with fewer alarm management interventions compared to conventional ventilation. IMPLICATIONS FOR CLINICAL PRACTICE: Automated ventilation may not reduce alarm frequency in neurocritical care patients, but the observed reduction in alarm-related bedside interventions suggests a potential benefit for nursing workload.

Humans

Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Dietary therapy is central to irritable bowel syndrome (IBS) management, yet the long-term durability of the low-FODMAP diet (LFD), and of microbiome-guided personalization, remains unclear. We assessed the long-term clinical and gut-microbiome effects of a microbiome-guided personalized diet (PD) compared with a standard LFD in adults meeting Rome IV criteria for IBS. In this multicenter, open-label randomized controlled trial with blinded outcome assessment, participants who completed a 6-week dietary intervention (PD or LFD) were followed at 6 and 12 months without further dietary intervention. Outcomes included the IBS Severity Scoring System (IBS-SSS), IBS Quality of Life (IBS-QOL), and the Hospital Anxiety and Depression Scale (HADS); gut microbiota were profiled by 16S rRNA sequencing. Longitudinal changes were evaluated using linear mixed-effects models, responder analyses, PERMANOVA, and PERMDISP. Both diets reduced IBS-SSS at 6 weeks. PD maintained symptom improvement at 6 and 12 months (-82.0 and -78.3 points from baseline), whereas LFD benefits regressed by 12 months (+29.3 points; between-group p&#x2009;=&#x2009;0.001). At 12 months, IBS-SSS responder rates were higher with PD than LFD (62.5% vs 34.5%; absolute risk difference&#x2009;+28.0%, 95% CI 4.2-47.7; Fisher p&#x2009;=&#x2009;0.029), and IBS-QOL, HADS-anxiety, and HADS-depression showed more favourable trajectories with PD. PD was associated with sustained Shannon alpha-diversity gains (+0.488 at 6 weeks;&#x2009;+0.205 at 12 months; both p&#x2009;<&#x2009;0.01). A modest between-group beta-diversity difference at 6 months (R2&#x2009;=&#x2009;0.035; p&#x2009;=&#x2009;0.011) was not significant at 12 months. This hypothesis-generating follow-up suggests more durable benefit with PD; larger trials powered for long-term clinical and microbiome outcomes are warranted.

Humans

The effect of dexmedetomidine in mechanically ventilated patients with sepsis and septic shock: a meta-analysis of randomized controlled trials.

PURPOSE: Dexmedetomidine (DEX) is a central sympatholytic with sedative properties widely used in critically ill patients. However, its effects in patients with sepsis and septic shock remain controversial. This meta-analysis evaluated the efficacy and safety of DEX compared to other sedatives in mechanically ventilated patients with sepsis and septic shock. METHODS: A systematic search was conducted across PubMed, Embase, Scopus, and Cochrane Library from inception through May 1, 2025 for randomized controlled trials comparing DEX with other sedatives or placebo in mechanically ventilated patients with sepsis and septic shock. Primary outcomes included overall mortality and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes encompassed duration of mechanical ventilation (MV), length of stay in Intensive Care Unit (ICU), incidence of hypotension and bradycardia. RESULTS: Fifteen studies involving 3,882 patients (1,945 in the DEX group, 1,937 in the control group) were included. DEX was demonstrated no significant differences compared to other sedatives or placebo in overall mortality (Risk Ratio [RR] 0.98, 95% Confidence Interval [CI] 0.90 to 1.07, p&#x2009;=&#x2009;0.71, I2&#x2009;=&#x2009;0%), SOFA scores (Mean Difference [MD]&#x2009;-&#x2009;0.14, 95% CI -0.81 to 0.52, p&#x2009;=&#x2009;0.67, I2&#x2009;=&#x2009;0%), length of stay in ICU (MD -0.32, 95% CI -1.69 to 1.06, p&#x2009;=&#x2009;0.65, I2&#x2009;=&#x2009;77%), or incidence of hypotension (RR 1.15, 95% CI 0.81 to 1.62, p&#x2009;=&#x2009;0.44, I2&#x2009;=&#x2009;14%). However, DEX significantly reduced the duration of MV (MD -0.54, 95% CI -0.98 to -0.10, p&#x2009;=&#x2009;0.02, I2&#x2009;=&#x2009;25%) but was associated with an increased incidence of bradycardia (RR 1.67, 95% CI 1.22 to 2.28, p&#x2009;=&#x2009;0.001, I2&#x2009;=&#x2009;0%). CONCLUSIONS: In mechanically ventilated patients with sepsis and septic shock, DEX shortened duration of MV but was associated increased bradycardia risk. No mortality or organ dysfunction benefits were observed. These findings suggest DEX is a reasonable therapeutic option to facilitate earlier ventilator weaning in selected patients (particularly those without shock), but careful monitoring for cardiovascular adverse effects is warranted.

Humans

Manual, digital, and AI tumour-infiltrating lymphocyte scoring: a secondary analysis of the APHINITY randomised trial.

BACKGROUND: Stromal tumour-infiltrating lymphocytes (sTILs) are prognostic in early-stage HER2-positive breast cancer, but their role in the context of dual HER2 blockade remains undefined. We evaluated manual, digital, and artificial intelligence (AI)-based sTIL quantification, together with AI-derived spatial metrics, for prognostic and treatment-benefit stratification using tumour samples from the phase 3 APHINITY trial. METHODS: In the APHINITY trial, 4805 patients were randomly assigned to receive chemotherapy plus trastuzumab with pertuzumab or chemotherapy plus trastuzumab with placebo. Median follow-up was 74&#xb7;1 months (IQR 68&#xb7;3-75&#xb7;4). We analysed 4262 haematoxylin and eosin-stained images using manual assessment, an automated digital approach, AI-based lymphocyte quantification (AI percentage lymphocytes), and two AI-derived spatial features (AI-TIL and immune hotspot). Interobserver reproducibility was assessed in 262 randomly chosen tumour samples scored independently by five pathologists. Multivariable Cox models were used to assess associations between TIL levels and invasive disease-free survival (primary outcome in APHINITY), distant recurrence-free interval, and overall survival. The heterogeneity of pertuzumab benefit was evaluated using subgroup analyses, subpopulation treatment effect pattern plot analyses, and nested Cox models with treatment-by-biomarker interaction terms. FINDINGS: Manual scoring showed high interobserver reproducibility (intraclass correlation coefficient 0&#xb7;84 [95% CI 0&#xb7;79-0&#xb7;88]). Concordance between manual and automated methods was modest. AI-based scoring (AI percentage lymphocytes) reclassified 120 (11&#xb7;6%) of 1035 node-positive tumours from immune-low (by manual scoring) to immune-high; this subgroup of patients showed greater separation of 5-year invasive disease-free survival curves between pertuzumab and placebo groups compared with patients whose tumours were concordantly classified as immune-low by both manual and AI-based approaches. Higher levels of TILs were associated with improved invasive disease-free survival for all sTIL measurement approaches and spatial measurements (hazard ratios [HRs] 0&#xb7;41-0&#xb7;93). Pertuzumab was associated with improved invasive disease-free survival at higher sTIL levels across all measurement approaches (HRs 0&#xb7;36-0&#xb7;48), but was not associated with higher values of spatial measures. The largest 6-year absolute improvements with pertuzumab were observed in patients with node-positive disease whose tumours scored in the highest level of immune infiltration of manual sTIL scoring (&#x2265;70&#xb7;0%; mean absolute improvement 12&#xb7;1 percentage points [SD 2&#xb7;8]). In nested prognostic and predictive models, AI-based immune hotspot scores provided the most consistent additional information when combined with any sTIL measurement (all p<0&#xb7;010). INTERPRETATION: Standardised manual sTIL scoring was reproducible, and digital and AI-based methods showed consistent prognostic stratification and potential for treatment-benefit stratification despite only modest correlation between platforms. AI spatial metrics provided complementary information beyond sTIL density and could support more scalable immune assessment. Future studies are needed to validate these approaches in independent cohorts and to clarify their clinical utility for stratifying contemporary HER2-directed therapies. FUNDING: None.

Humans

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist&#xa0;=&#xa0;max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median &#x394; -21.0&#xa0;ms; 95% CI -33.9 to -18.6; p&#xa0;<&#xa0;0.001). Signed VED16 did not change significantly (median &#x394; 0.4&#xa0;ms; p&#xa0;=&#xa0;1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median &#x394; -5.2&#xa0;ms; p&#xa0;=&#xa0;0.070), whereas dist decreased significantly (median &#x394; -0.7&#xa0;ms; 95% CI -14.4 to 0.0; p&#xa0;=&#xa0;0.015). The proportion of patients within the normal dyssynchrony band (|VED16|&#xa0;&#x2264;&#xa0;20&#xa0;ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r&#xa0;=&#xa0;-0.45, p&#xa0;=&#xa0;0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

Humans

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans

Age-related differences in semen quality in Holstein-Friesian bulls: a paired within-bull comparison of early and mature reproductive stages.

Genomic selection has changed dairy cattle breeding by increasing the use of young bulls for artificial insemination and shortening the reproductive lifespan of sires. Under these conditions, semen quality at the beginning of commercial use has become an important practical issue. Semen samples from 39 fertile Holstein-Friesian bulls used for commercial AI were collected between 2013 and 2016, during the introduction of genomic selection in Poland. This paired within-bull study compared semen collected from the same bulls at an early reproductive stage (13-20 months; young bulls, YB) and at full maturity (5-6 years; mature bulls, MB). The evaluation included conventional ejaculate traits, CASA-derived motility and kinematic descriptors, mtDNA copy number, and mitochondrial content per sperm cell. Importantly, all ejaculates met the quality requirements for commercial insemination. Ejaculate volume, sperm concentration, mitochondrial DNA copy number, and mitochondrial content did not differ significantly between age groups. The CASA-derived sperm movement profile, in contrast, differed with age. Semen from young bulls showed a higher proportion of progressively motile spermatozoa, whereas semen from mature bulls showed higher velocity-related parameters, including VSL, VCL, and STR. These findings indicate that bull age mainly affected sperm movement characteristics rather than semen output or mitochondrial content. Overall, the results support the use of young bulls in artificial insemination programs and show that age-related differences in semen quality are expressed mainly through changes in the post-thaw sperm motility and kinematic profile.

Animals

An allograft inflammatory factor enhances sperm viability by modulating intracellular calcium in oyster Crassostrea gigas.

As an important aquaculture bivalve, the Pacific oyster Crassostrea gigas faces severe constraints in artificial reproduction, where low sperm motility often leads to fertilization failure and limits the sustainable development of the oyster aquaculture industry. In the present study, the variation of sperm from different oyster individuals was observed, and high-quality sperm possessed intact, elongated flagella with no structural abnormalities, while low-quality sperm showed shortened flagella with frequent tangling or coiling defects. Transcriptomic analysis comparing high- and low-quality sperm revealed significantly reduced expression of genes associated with sperm motility and release (CgAIF1, CgAchR, CgSEX), sperm quality and development (CgEP4, CgIFi2b), and cryoprotection (CgISPs) in low-quality sperm. Notably, an allograft inflammatory factor (designed as CgAIF1) encoding EF-hand domain, known as Ca2+ binding activity, was among the most significantly downregulated in low-motility sperm. CgAIF1 is highly expressed in haemocytes, ganglia, and gonads of oysters. Incubation with the recombinant AIF1 protein (rCgAIF1) significantly improved sperm curvilinear velocity, thereby enhancing the overall motility of C. gigas sperm. Furthermore, rCgAIF1 incubation increased intracellular Ca2+ levels (2.13-fold at 30&#xa0;min, 2.71-fold at 60&#xa0;min) and superoxide dismutase (SOD) activity (1.44-fold at 30&#xa0;min, 1.24-fold at 60&#xa0;min) in sperm, suggesting potential roles in calcium homeostasis regulation and antioxidant defense. In conclusion, this study demonstrates that CgAIF1 significantly enhances motility of oyster sperm, providing a scientific basis for artificial breeding and seed production in oyster aquaculture.

Animals

Integrative machine learning and transcriptomic analysis reveals molecular mechanisms underlying low survival rate in larval Chinese Bahaba (Bahaba taipingensis).

Chinese Bahaba (Bahaba taipingensis) is a Class I protected marine fish endemic to China. Low larvae survival during artificial breeding severely hinder population recovery. To investigate the molecular mechanism of high mortality in larval fish, this study performed RNA-seq on liver from naturally deceased (ND) and mass-dead (MD) individuals, combined with least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithms to screen for core signature genes. A total of 873 differentially expressed genes (DEGs) were identified, including 112 upregulated and 761 downregulated genes. GO and KEGG enrichment analyses revealed significant enrichment in amino acid metabolism disorders, one&#x2011;carbon folate pool impairment, PPAR signaling abnormalities, ECM-receptor interaction, focal adhesion pathway, indicating widespread metabolic suppression accompanied by extracellular matrix remodeling and signaling disturbances in the livers of MD fish. MAD pre-filtering combined with dual machine learning algorithms yielded 18 robust core signature genes, among which SLC38A4, MMP1, FADD, FKBP5, and APOB were consistently identified as high-frequency core genes by both algorithms. SLC38A4 exhibited the highest importance score in the RF model and was significantly downregulated, making it the primary molecule distinguishing ND from MD phenotypes. ROC curve analysis showed that both models achieved an AUC of 1.000 (95% CI lower bound: 0.610), confirming the precise discriminatory ability of the core genes. GSEA further demonstrated significant enrichment of this core gene set in ND samples. This study provides the first systematic elucidation of the molecular mechanisms underlying liver dysfunction in low survival rate B. taipingensis, characterized by amino acid transport impairment, metabolic reprogramming, and structural remodeling, offering theoretical foundations for health assessment, early mortality risk warning, and artificial breeding conservation of this species.

Animals

Machine learning-assisted Mn-N-C nanozyme colorimetric sensor array for trace-level detection of biogenic amines in meat.

Accurate detection of biogenic amines (BAs) in meat remains challenging due to their high structural similarity and co-occurrence. Herein, an Mn-N-C nanozyme was synthesized via a metal-organic framework confined pyrolysis strategy, possessing excellent oxidase (OXD)- and peroxidase (POD)-like activities. The dual enzyme-like activity showed Km values of 0.1584&#xa0;mM (OXD) and 0.1498&#xa0;mM (POD), respectively, in detection system. Leveraging these properties, a colorimetric sensor array was constructed, enabling the detection of four representative BAs within a concentration range of 2-10&#xa0;ppm with 100% classification accuracy. In addition, a concentration independent recognition model based on an artificial neural network was developed to address signal nonlinearity interference in meat. The integrated system achieved accurate trace-level identification of BAs in perishable fish, pork, and chicken, demonstrating its applicability for early-stage BAs monitoring and quality deterioration warning during storage and transportation.

Biogenic Amines

A review into the recent advances in the world of amoebiasis.

PURPOSE OF REVIEW: Amoebiasis is a parasitic infection caused by Entamoeba histolytica , affecting 10% of the global population. It is a well recognized cause of morbidity and mortality in low-middle-income countries where it is endemic. However, with increased migration and global travel, amoebiasis is now more common in high-income countries, although diagnosis is often delayed or even missed due to lack of awareness of the latest epidemiology and optimal diagnostic testing. This review discusses the evolving prevalence, and the current international guidelines for the investigation and treatment of amoebiasis, focusing on recent advances. RECENT FINDINGS: The recent literature shows that the primary investigations for amoebiasis remain the same, though newer modalities such as artificial intelligence-powered microscopy and metagenomics have been developed recently, which aids the accuracy and speed of diagnosis. Treatment remains the same, though current research has found potential new drugs and drug targets which show promise. SUMMARY: This review reinforces the importance of early clinical suspicion, diagnosis and treatment for amoebiasis. What was once a disease only seen in endemic countries or travel-associated imported cases is now more common and must not be missed.

Humans