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Impact of adenosine in controlled aortic root reperfusion on clinical outcomes among patients undergoing valvular heart surgery.

BACKGROUND: Adenosine is a vital medication in cardiac surgery, particularly in valvular heart procedures. While its use has been linked to improved postoperative cardiac function in some studies, there remains significant uncertainty regarding the adenosine usage in aortic reperfusion phase. This lack of consensus poses challenges for surgeons, perfusionists, and anesthesiologists alike. This study aims to explore the impact of adenosine on clinical outcomes in patients undergoing valvular heart surgery. METHOD: This prospective randomized controlled trial was conducted over a three-month period. Sixty patients undergoing valvular heart surgery were enrolled using a continuous sampling method and randomly allocated into two equal groups of 30 patients each. The intervention group received adenosine-enriched aortic root reperfusion immediately prior to aortic declamping, while the control group underwent standard warm blood aortic root reperfusion. Both groups were matched for demographic and clinical characteristics to ensure comparability. RESULTS: Results indicated no significant differences in mean cardiopulmonary bypass (CPB) time, aortic cross-clamping duration, or mechanical ventilation between the intervention and control groups. However, the intervention group that received adenosine had a higher rate of antiarrhythmic agent usage in the operating room (P&#xa0;<&#xa0;0.05). Inotropic agent usage was similar in both groups during surgery and in the ICU. Additionally, laboratory parameters on the first day of ICU admission were comparable between groups. CONCLUSION: Results in the control group showed more favorable outcomes in terms of anti-arrhythmic drug usage, electroshock application, and arrhythmia prevalence. This study showed advantages for the standard warm blood aortic root reperfusion technique in managing post-operative cardiac rhythm disturbances, in comparison with the trial group.

Humans

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781)&#x2009;=&#x2009;11.238, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.142), as well as significant main effects on time (F(11, 781)&#x2009;=&#x2009;6.809; P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.091) and group effects (F(1, 71)&#x2009;=&#x2009;26.707, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142)&#x2009;=&#x2009;20.747, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.234) and depression levels (F(2, 142)&#x2009;=&#x2009;22.277, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r&#x2009;=&#x2009;0.335, P&#x2009;<&#x2009;0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

Humans

Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120&#xa0;dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (-&#xa0;21%) and silent period duration (-&#xa0;23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans

Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.

OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75&#xa0;% of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p&#xa0;<&#xa0;0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p&#xa0;<&#xa0;0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.

Humans

Sodium Glucose Co-Transporter 2 Inhibitors and Ventricular Arrhythmias in Patients with Type 2 Diabetes: A Systematic Review of Observational Studies.

BACKGROUND: Sodium glucose co-transporter 2 inhibitors (SGLT2i) may exert antiarrhythmic effects, but their association with ventricular arrhythmias remains unclear. OBJECTIVE: We conducted a systematic review to evaluate the association between SGLT2i use and the risk of ventricular arrhythmias, cardiac arrest, and sudden cardiac death compared with other antidiabetic medications or no SGLT2i use among patients with type 2 diabetes mellitus. METHODS: MEDLINE, EMBASE, and CENTRAL were searched for observational studies published between March 2013 and March 2026. Quality was assessed using the Risk of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool, alongside evaluation of pharmacoepidemiology-specific biases. RESULTS: A total of 17 studies (16 cohort and one nested case-control) were included. Based on ROBINS-I, seven studies had moderate, eight serious, and two critical risks of bias. Eleven studies had at least one pharmacoepidemiology-specific bias. For ventricular arrhythmias, estimates ranged from a protective effect (hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.04-0.97) to a potential increased risk (odds ratio 1.87, 95% CI 0.89-3.95) with SGLT2i use. For cardiac arrest, estimates consistently reported a lower risk with estimates that ranged from HR 0.63 (95% CI 0.59-0.68) to HR 0.85 (95% CI 0.82-0.88). The only study on sudden cardiac death reported a potential risk reduction (HR 0.62, 95% CI 0.38-1.01). CONCLUSIONS: While the association between SGLT2i and ventricular arrhythmias remains inconsistent, the use of SGLT2i likely reduces cardiac arrest and may reduce sudden cardiac death, suggesting a possible protective effect on ventricular arrhythmias among patients with type 2 diabetes.

Journal Article

Fundamentals of pacemakers ECG interpretation - part 2.

BACKGROUND: Modern pacemakers incorporate arrhythmia-response algorithms, ventricular pacing minimization protocols, and safety mechanisms that generate ECG patterns indistinguishable from pathological AV block, sensing malfunction, or device-mediated tachycardia. Failure to recognize these algorithm-driven signatures leads to unnecessary interventions, misdiagnosis, and inappropriate device reprogramming. This manuscript is the second in a two-part series on pacemaker ECG interpretation. METHODS: We conducted a narrative review of peer-reviewed literature and device-specific documentation on algorithm-driven ECG behavior, synthesizing evidence across arrhythmia recognition, upper rate physiology, ventricular pacing minimization, mode switching, safety mechanisms, and hysteresis algorithms. RESULTS: Pacemaker-mediated tachycardia produces regular paced wide-complex tachycardia locked at the upper tracking rate, initiated by any event with retrograde VA conduction. Ventricular tachycardia is identified by QRS morphology diverging from the known paced pattern, absent pacing spikes, and AV dissociation. Upper rate Wenckebach behavior mimics Mobitz type I AV block; 2:1 upper rate response mimics second-degree AV block. Ventricular pacing minimization algorithms produce isolated nonconducted P waves and prolonged AV intervals that simulate pathological conduction disease. Mode switching causes abrupt rate drops misidentified as output failure. Ventricular safety pacing generates a conspicuously short, fixed AV interval. Three discrete pacing artifacts reflect AV-sequential cardiac resynchronization therapy (CRT), ventricular safety pacing in CRT, or His-bundle pacing with backup RV output. Rate and AV hysteresis produce pauses and wandering AV intervals mimicking oversensing or Wenckebach periodicity. CONCLUSIONS: Recognizing algorithm-driven ECG patterns requires knowledge of device timing intervals and refractory periods, which lets clinicians distinguish programmed behavior from true malfunction or cardiac arrhythmia.

Humans

Impact of smoking on structural failure after arthroscopic rotator cuff repair: a systematic review and meta-analysis.

BACKGROUND: Rotator cuff tears cause significant shoulder pain and functional limitation. Arthroscopic rotator cuff repair improves symptoms, yet structural failure rates remain substantial. Smoking may impair tendon-to-bone healing, but clinical studies report mixed findings due to heterogeneous methodology. Therefore, a systematic synthesis of imaging-confirmed outcomes is needed to clarify the association between smoking and structural failure after arthroscopic rotator cuff repair. METHODS: This review followed PRISMA 2020 and was registered in PROSPERO (CRD420251246197). PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 12 December 2025. Comparative clinical studies of adults undergoing arthroscopic rotator cuff repair that reported imaging-confirmed structural integrity (magnetic resonance imaging or ultrasonography) at &#x2265;6 months were included. Two reviewers independently screened studies, extracted data, and assessed quality using the Newcastle-Ottawa Scale. The primary outcome (structural failure) was pooled as risk ratios using a random-effects model with the restricted maximum likelihood estimator and Hartung-Knapp adjustment. Secondary continuous outcomes were synthesized using Bayesian random-effects models; subgroup, sensitivity, and meta-regression analyses explored heterogeneity. RESULTS: Ten cohort studies (1,683 shoulders) were included. Smoking was associated with a higher risk of imaging-confirmed structural failure (risk ratio 1.53; 95% confidence interval 1.13-2.08; P = .011) with low heterogeneity (I2 = 24.7%). Subgroup and sensitivity analyses supported robustness, with no evidence of effect modification by region, follow-up duration, tear size, or smoking definition. Meta-regression showed no significant influence of age, smoking prevalence, or diabetes prevalence on the pooled effect. Secondary outcomes (3 studies) suggested slightly lower postoperative American Shoulder and Elbow Surgeons scores among smokers, while visual analog scale pain scores and forward flexion showed no clear between-group differences. No publication-bias signals were detected for the primary outcome. CONCLUSION: Smoking is associated with a higher risk of imaging-confirmed structural failure after arthroscopic rotator cuff repair. Functional outcomes were broadly similar between groups, with only a small, likely clinically negligible reduction in American Shoulder and Elbow Surgeons scores among smokers. These findings support careful smoking history assessment and perioperative risk modification, including smoking cessation strategies.

Humans

Cerebellar iTBS enhances gait adaptation by modulating cortical sensorimotor network dynamics: a randomized controlled trial.

Gait adaptation enables individuals to maintain locomotor stability under persistent perturbations. Although the cerebellum is critical for sensory prediction error-based (SPE) adaptation, how cerebellar neuromodulation reshapes cortical sensorimotor networks to enhance gait adaptation remains unclear. This study investigated the behavioral effects and underlying cortical neurodynamic mechanisms of cerebellar intermittent theta-burst stimulation (iTBS) on gait adaptation. Thirty-two healthy adults received either active or sham cerebellar iTBS. Participants performed a split-belt treadmill adaptation task before and after intervention. Cortical responsiveness was evaluated using TMS-evoked EEG over primary motor cortex (M1), while resting-state EEG was analyzed to assess spectral power and directional functional connectivity. Compared to sham, cerebellar iTBS significantly enhanced gait adaptation, evidenced by a faster adaptation rate (p&#x202f;=&#x202f;0.035) and enhanced Early Adaptation SLS (p&#x202f;=&#x202f;0.011), without altering initial perturbation responses or post-adaptation outcomes. The iTBS increased TMS-evoked &#x3b1; (p&#x202f;=&#x202f;0.031) and &#x3b3; (p&#x202f;=&#x202f;0.022) power in M1, while the &#x3b1; power was correlated with faster adaptation (r&#x202f;=&#x202f;0.526, p&#x202f;=&#x202f;0.002). Furthermore, iTBS strengthened PPC-to-M1 directed connectivity in the &#x3b2; (p&#x202f;=&#x202f;0.025) and &#x3b3; (p&#x202f;=&#x202f;0.013) bands. Enhanced parieto-motor directionality were positively associated with adaptation rate (&#x3b2;: r&#x202f;=&#x202f;0.515, p&#x202f;=&#x202f;0.003; &#x3b3;: r&#x202f;=&#x202f;0.463, p&#x202f;=&#x202f;0.009). These findings suggest that cerebellar iTBS facilitates gait adaptation by modulating cortical responsiveness and directional sensorimotor network connectivity, providing multi-level neurodynamic evidence for the cerebello-cortical modulation during gait adaptation and offering a strong physiological rationale for targeted neuromodulation in gait rehabilitation strategies.

Humans

Selective monitoring of trace-level catechin and myricetin in herbal and aqueous matrices using magnetic MIP-DSPME: Optimization via design of experiments.

A novel dispersive solid-phase microextraction approach utilizing a magnetic molecularly imprinted polymer (MMIP) integrated with HPLC-UV detection was developed for the concurrent quantification of catechin and myricetin in herbal extracts and aqueous samples. The sorbent was engineered as a core-shell nanocomposite, consisting of a selective polymer layer deposited onto Fe3O4@SiO2-APTMS magnetic nanoparticles. Dual-template imprinting using catechin and myricetin generated complementary binding cavities within the polymer framework. Experimental variables influencing extraction were systematically screened and subsequently optimized. A Plackett-Burman design was first applied to identify the most influential factors, with pH and sorption time identified as the dominant variables. These parameters were subsequently fine-tuned using a central composite design, and the optimization process was completed in only 30 experimental runs. The sorption characteristics of the imprinted sorbent (MMIP) were compared with those of its non-imprinted counterpart (MNIP). The MMIP demonstrated markedly higher maximum binding capacities (Qmax), reaching 119.3&#xa0;mg&#xa0;g-1 for myricetin and 112.1&#xa0;mg&#xa0;g-1 for catechin, whereas the corresponding values for the MNIP were 32.55 and 32.08&#xa0;mg&#xa0;g-1, respectively. Moreover, the affinity constants (KL&#xa0;=&#xa0;0.760-0.950&#xa0;L&#xa0;mg-1) were approximately 2.3-fold higher for the MMIP, confirming its stronger and more selective interactions with the target analytes. The selectivity coefficients for the targeted flavonoids relative to structurally related compounds, including ferulic acid, p-coumaric acid, melatonin, and curcumin, exceeded 3.5 for the MMIP, whereas the corresponding values for the MNIP were close to 1.1, demonstrating the high molecular recognition capability of the imprinted sorbent. Method validation demonstrated limits of detection (LODs) of 0.33-0.59&#xa0;ng&#xa0;mL-1 and limits of quantification (LOQs) of 1.10-1.96&#xa0;ng&#xa0;mL-1, and excellent linearity over the concentration range of 5.0-5500&#xa0;ng&#xa0;mL-1 (R2&#xa0;>&#xa0;0.998). The method achieved recoveries of 93.96% to 105.69% with RSDs below 5.5%, while the preconcentration factors ranged from 209 to 229. Furthermore, the sorbent retained more than 95% of its extraction efficiency after four consecutive reuse cycles and more than 80% after six cycles, demonstrating excellent stability and reusability. The proposed method was successfully applied to the analysis of six medicinal plant extracts and water samples, showing negligible matrix interference and superior sensitivity, selectivity, and operational simplicity compared with conventional solid-phase extraction methods.

Flavonoids

Morphology-Encoded Colorimetric Hydrogen Sensing Using Embedded Reactive Pd Absorbers in Fabry-Perot Cavities.

Chemical reactions offer a powerful strategy for generating visible optical responses through localized changes in absorption, dielectric environment, and interfacial wetting. A palladium (Pd)-embedded Fabry-Perot cavity is introduced as a reaction-active optical platform in which structural color is governed by intracavity absorption coupled with reaction-induced dielectric perturbation. Positioning Pd within the dielectric spacer creates a spatially controllable reactive absorber whose vertical location relative to the standing-wave field dictates wavelength-selective absorption within the cavity. The morphology of the embedded Pd layer provides an additional design parameter by modulating both optical loss and interfacial wetting. Under hydrogen exposure in the presence of oxygen, catalytic water formation at the Pd/polymer interface generates localized dielectric heterogeneity and interfacial water droplets, thereby perturbing the optical path length and amplifying the visible response. As a result, the cavity exhibits pronounced, morphology-dependent color transitions that are inaccessible through dielectric-layer engineering or Pd/PdH refractive-index changes alone, enabling direct visual hydrogen sensing under ambient light, as well as flexible optical devices capable of large-area patterning. These findings establish a design framework for reaction-active optical cavities that translate localized chemistry into a colorimetric hydrogen sensing mechanism.

Fabry&#x2013;Perot resonator

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid &#x3b1;-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient &#x2264;66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score &#x2265;7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin&#x2009;&#x2264;&#x2009;18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin&#x2009;&#x2264;&#x2009;18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the&#x2009;&#x2265;&#x2009;11-&#x2009;&#x2264;&#x2009;18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

Humans

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 &#xb1; 178.8 mL) but negative in the SBUF-SMUF group (-105.0 &#xb1; 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 &#xb1; 70.2 vs. 261.0 &#xb1; 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 &#xb1; 1.03 vs. 2.27 &#xb1; 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans

Isometric Exercises for Tendinopathies: A Systematic Literature Review.

PURPOSE: Musculoskeletal disorders are among the most common reasons for medical consultation, with tendinopathies accounting for up to 30% of such presentations. Although exercise remains the cornerstone of management, the most effective modality continues to be debated. Eccentric exercise has long been the mainstay, but the role of isometric exercise in pain modulation and functional recovery remains unclear. This systematic review aims to evaluate the current evidence on the efficacy of isometric exercises in the management of tendinopathies across various anatomic sites. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to August 1, 2025. Eligible studies included randomized controlled trials and prospective or retrospective cohort studies assessing isometric exercise interventions for tendinopathy, with or without comparator groups. Case series and case reports were excluded. Data extracted included participant demographic characteristics, site of tendinopathy, symptom duration, treatment duration, adherence, and outcome measures such as Victorian Institute of Sports Assessment (A, P, or G), visual analog scale, Patient-Specific Functional Scale, 36 item short form health survey (SF-36), and EuroQol 5-Dimension questionnaires. Imaging outcomes (ultrasound or magnetic resonance imaging) were recorded where available. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. FINDINGS: The search identified 304 articles, of which 13 randomized controlled trials met the inclusion criteria, encompassing 336 participants (40% female). Tendinopathy sites included the patellar (n = 4), Achilles (n = 3), lateral elbow (n = 2), rotator cuff (n = 2), wrist extensor (n = 1), and gluteal (n = 1) tendons. Median symptom duration was 23 months (interquartile range, 3-51 months). Intervention periods ranged from a single 45-minute session to 4-month exercise programs. Treatment adherence was high initially (nearly 100%) but declined over time, with 70% of participants in the isometric and 58% in the control (isotonic) groups completing &#x2265;80% of sessions. Pain reduction and functional improvement were statistically significant in only 3 studies. Imaging-based outcomes were inconsistently reported, and study heterogeneity precluded meta-analysis. Overall methodological quality was rated as good in 3 studies and poor in 10. IMPLICATIONS: Current evidence provides limited support for the superiority of isometric exercise in tendinopathy management. Although isometric regimens appear tolerable and may confer short-term analgesic benefits, their long-term efficacy relative to eccentric or isotonic protocols remains uncertain. Future research should prioritize standardized outcome measures, longer follow-up, and uniform diagnostic criteria to strengthen the evidence base for exercise prescription in tendinopathies.

Humans

Effects of H-coil TMS on suicidality in major depression: A secondary analysis of data from a multisite randomized trial comparing accelerated to once-a-day stimulation.

Suicide is the 10th leading cause of death in US adults. Standard once-daily repetitive transcranial magnetic stimulation (rTMS) can reduce suicidal ideation. Yet, antidepressant and anti-suicidal effects often take several weeks to emerge, while rapid improvement is often required. Accelerated TMS has been proposed as a strategy to hasten therapeutic response. A recent FDA-regulated multicenter trial evaluated accelerated intermittent theta burst Deep TMS with the H1-coil versus standard high-frequency Deep TMS in MDD. Both groups demonstrated high remission and response rates for depression, with the accelerated protocol showing non-inferiority and a shorter time to remission. The goal of this exploratory secondary analysis was to evaluate the impact of these two H-coil TMS dosing paradigms on suicidal ideation. The Scale for Suicide Ideation (SSI), as well as suicidality items of HDRS, MADRS and CUDOS were collected and analyzed. On all scales, both accelerated and standard Deep TMS protocols were associated with meaningful reductions in suicidality. The accelerated protocol achieved a faster onset of improvement. Comparison between the timeline of improvement in suicidality and in overall depressive symptoms found a trend for faster improvement in suicidality, especially with the accelerated protocol. These findings highlight the importance of treatment frequency in determining time to clinical benefit and support the use of scalable accelerated protocols for patients requiring more rapid symptom relief.

Humans

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24&#x2009;hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125&#x2009;mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95%&#x2009;CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans

Recurrent myocardial infarction identified by centralized troponin review: Insights from the MINT trial.

BACKGROUND: The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS: The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS: Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS: In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

Humans

Feasibility and efficacy of left bundle branch area pacing guided by modified chest lead 1.

BACKGROUND: Left bundle branch area pacing (LBBAP) typically requires 12&#x2011;lead electrocardiogram (ECG) measurements using an electrophysiology (EP) recording system. However, a simplified approach using modified chest lead 1 (MCL1) is potentially feasible. This study aimed to compare the success rate and pacing outcomes of LBBAP guided by MCL1 with those guided by the 12&#x2011;lead ECG using an EP recording system. METHODS: This retrospective, single-center study included patients with preserved left ventricular ejection fraction who underwent LBBAP for bradyarrhythmia. LBBAP was either guided by 12&#x2011;lead ECG using an EP recording system or by MCL1. In the MCL1 group, a follow-up examination with a 12&#x2011;lead ECG using an EP recording system was conducted within one week postoperatively. RESULTS: A total of 65 patients underwent LBBAP (EP recording system group: n&#xa0;=&#xa0;35; MCL1 group: n&#xa0;=&#xa0;30). The overall success rate of LBBAP was 84.6%, with no significant difference between groups (88.5% vs. 80.0%, p&#xa0;=&#xa0;0.49). No significant differences were observed in the paced QRS duration (140.4&#xa0;&#xb1;&#xa0;8.0 vs. 141.9&#xa0;&#xb1;&#xa0;13.1&#xa0;ms, p&#xa0;=&#xa0;0.54), V6-V1 interpeak interval (39.7&#xa0;&#xb1;&#xa0;16.5 vs. 38.3&#xa0;&#xb1;&#xa0;15.6&#xa0;ms, p&#xa0;=&#xa0;0.79), or V6 R-wave peak time (69.8&#xa0;&#xb1;&#xa0;12.3 vs. 71.5&#xa0;&#xb1;&#xa0;12.1&#xa0;ms, p&#xa0;=&#xa0;0.68). CONCLUSIONS: MCL1-guided LBBAP was feasible and achieved a high success rate, with outcomes comparable to those of conventional EP recording system-guided implantation. This simplified approach may reduce procedural complexity and may allow LBBAP implantation without the routine use of an EP recording system.

Humans