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Diagnostic and prognostic value of fibroblast growth factor 23 in acute kidney injury: systematic review and meta-analysis.

Background: Acute kidney injury (AKI) is associated with high mortality and adverse outcomes. Fibroblast growth factor 23 (FGF23) has emerged as a potential biomarker for AKI; however, its diagnostic and prognostic utility remains inconsistent.Methods: We conducted a systematic review and meta-analysis of studies evaluating circulating intact FGF23 (iFGF23) or C-terminal FGF23 (cFGF23) (PROSPERO: CRD42022302659). PubMed, EMBASE, CNKI, and Wanfang databases were searched through June 9, 2026. QUADAS-2 was used for quality assessment. A random-effects bivariate model pooled sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (SROC AUC).Results: Twenty-three studies were included: 17 diagnostic, 6 prognostic (one addressing both). For AKI diagnosis, the pooled sensitivity was 0.79 (95% CI 0.73-0.86), specificity 0.82 (95% CI 0.75-0.89), PLR 4.40 (95% CI 2.59-6.21), NLR 0.25 (95% CI 0.16-0.34), DOR 17.49 (95% CI 8.67-35.16), and SROC AUC 0.87 (95% CI 0.81-0.92). Substantial heterogeneity was observed (I2 = 67%), with iFGF23 demonstrating higher accuracy than cFGF23 (AUC 0.91 vs 0.81). For AKI mortality, pooled sensitivity was 0.77 (95% CI 0.69-0.84), specificity 0.76 (95% CI 0.70-0.82), DOR 10.89 (95% CI 6.86-17.30), and SROC AUC 0.77 (95% CI 0.70-0.83). Significant heterogeneity was noted (I2 = 86.2% for sensitivity, 80.4% for specificity). No significant publication bias was detected.Conclusions: Circulating FGF23 exhibits moderate-to-high diagnostic and moderate prognostic performance in AKI, though interpretation is limited by substantial heterogeneity. It may serve as a complementary biomarker for risk stratification, pending further validation with standardized protocols.

Humans

Genome-wide characterisation of the myosin light chain gene family in Chinese perch (Siniperca chuatsi) and its expression patterns in muscle fibre types and injury response.

The Class II myosin light chain (myl) genes in Chinese perch (Siniperca chuatsi) have not yet been systematically characterised, and relationships with muscle fibre specification, development, and injury-associated remodelling remain unclear. In this study, fast and slow muscle fibres were initially distinguished using myofibrillar ATPase histochemistry. Subsequently, genome-wide mining identified 16 Class II myl genes, comprising eight essential and eight regulatory light-chain subunits. Their conserved-domain features, chromosomal distribution, phylogenetic relationships and expression profiles were analysed. Transcriptomic profiling showed that summed myl transcript abundance was higher in fast muscle than in slow muscle, accounting for 67.2% of the pooled myl transcript pool across the two muscle types (paired t-test, raw P = 0.036). mylpfa, myl1 and mylz3 were the major fast-muscle-associated genes, whereas myl10, myl2b and myl13 were preferentially expressed in slow muscle at the transcript level. These patterns support these genes as candidate fibre-type-associated expression markers. Developmental profiling identified stage-associated myl expression patterns, including a possible expression shift between mylpfb and mylpfa. In the descriptive injury-repair time course (d0-d7), FPKM profiles indicated that fast-muscle-associated genes (mylpfa, mylz3 and myl1) were lower at d1 and recovered by d3, whereas several slow-muscle-associated genes showed biphasic transcript-level increases. The slow-muscle-associated RLC gene mylpfb showed a delayed expression peak at d7. Notably, the embryonic isoform myl6l showed a modest increase from approximately 2 FPKM at d0 to 4-5 FPKM after injury, suggesting a possible injury-associated expression pattern that requires further validation. Together, these findings provide a genome-wide description of the Chinese perch myl gene family and identify candidate fibre-type-associated genes and descriptive injury-associated isoform expression patterns.

Animals

Safety and outcomes of dapagliflozin initiation in critically ill patients with acute kidney injury: A post-hoc analysis of the defender trial.

BACKGROUND: SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS: Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS: Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS: Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.

Humans

Effectiveness of hyperbaric oxygen in traumatic brain injury patients: A systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is the most common neurological disorder and a leading cause of global mortality and disability. Although growing evidence suggests potential benefits of Hyperbaric Oxygen Therapy (HBOT) for TBI, its efficacy remains controversial. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from inception to March 2026. Randomized controlled trials (RCTs) evaluating HBOT versus any comparator including sham, standard care and no treatment in adults with TBI were included. Two independent reviewers screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias tool. Heterogeneity was assessed using the I² statistic. Effect sizes were pooled using random/fixed-effects models per heterogeneity results. RESULTS: 8 studies involving 570 participants were included. HBOT significantly improved computerized cognitive performance (SMD = 0.23, 95% CI: 0.07-0.40, p = 0.004, I² = 0%), executive function and processing speed (SMD = -0.59, 95% CI: -0.93 to -0.26, p = 0.0005, I² = 30%), memory function (SMD = 0.33, 95% CI: 0.03-0.63, p = 0.03, I² = 0%), and sleep quality (MD = 1.98, 95% CI: 0.07-3.88, p = 0.04, I² = 65%). No significant benefits were observed for Glasgow Outcome Scale (RR = 1.57, 95% CI: 0.55-4.44, I² = 87%), PTSD symptoms (MD = -3.05, 95% CI: -7.05-0.95, I² = 67%), neurobehavioral symptoms (MD = -9.06, 95% CI: -32.13-14.00, I² = 97%), and emotional distress (SMD = 0.25, 95% CI: -0.32-0.81, I² = 85%). Most adverse events were mild and transient. CONCLUSION: HBOT demonstrates domain‑specific benefits for cognitive function and sleep quality in TBI patients, predominantly those with mild TBI. However, evidence for PTSD, neurobehavioral symptoms, and emotional distress remains uncertain. Furthermore, the applicability of current evidence to moderate-to-severe TBI populations is restricted.

Humans

Oro-esophageal feeding for tracheostomized patients with severe traumatic brain injury: a randomized controlled trial.

BACKGROUND: This study reports the clinical effects of intermittent oro-esophageal tube feeding (IOE) versus nasogastric tube feeding (NGT) on nutritional status, aspiration pneumonia, decannulation, and level of consciousness in tracheostomized patients with severe traumatic brain injury (sTBI). METHODS: A randomized controlled trial was conducted between March 2024 and October 2025 in China and included tracheostomized patients with sTBI. Participants were randomized 1:1 to the intervention and control groups for 28-day interventions. IOE or NGT was used for nutritional supports, respectively. The primary outcome was nutritional status, including hemoglobin, albumin, prealbumin and body mass index. The secondary outcomes included aspiration pneumonia, decannulation, and level of consciousness assessed using the Glasgow Coma Scale (GCS). Generalized linear mixed-effects models, generalized estimating equations, and Cox regression were used for data analyze. RESULTS: A total of 104 participants were included in the analysis. After intervention, significant interaction effects were observed in hemoglobin (&#x3b2;&#x2009;=&#x2009;5.272, 95% CI: 2.707, 7.837), albumin (&#x3b2;&#x2009;=&#x2009;3.675, 95% CI: 1.854, 5.496), prealbumin (&#x3b2;&#x2009;=&#x2009;11.835, 95% CI: 6.623, 17.047), body mass index (&#x3b2;&#x2009;=&#x2009;1.719, 95% CI: 0.868, 2.569), the GCS (&#x3b2;&#x2009;=&#x2009;0.981, 95% CI: 0.572, 1.390), and aspiration pneumonia (OR= 0.304, 95% CI: 0.133, 0.693). The Cox model revealed that group significantly influenced the decannulation outcomes [HR (95% CI) =5.556 (3.197, 9.657), p&#x2009;<&#x2009;0.001]. CONCLUSIONS: In tracheostomized patients with sTBI who received routine treatment, IOE is more conducive to decannulation and the improvement in nutritional status, aspiration pneumonia, and level of consciousness than NGT. CLINICAL TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT06328985, 03/18/2024, clinicaltrials.gov/study/NCT06328985).

Humans

Accurate quantification of canine mitochondrial DNA copy number from canine blood and brain samples.

Acute brain injury is difficult to evaluate in veterinary medicine and tools to investigate the potential involvement of mitochondrial involvement are limited. The brain is highly enriched in mitochondria and contains thousands of copies of mitochondrial DNA (mtDNA) per cell, but robust methods for quantifying mitochondrial DNA copy number (mtDNA-CN) in canine tissues are lacking. We describe the development of a quantitative real-time PCR assay for absolute measurement of mtDNA-CN which was validated in canine blood and brain tissue. To minimize amplification of nuclear mitochondrial insertion sequences (NumtS) and repetitive regions, species-specific oligonucleotide primers were designed following in silico genomic filtering. The assay was applied to a small pilot cohort comprising blood samples from dogs with and without acute brain injury (n&#xa0;=&#xa0;4-6 per group) and cerebral cortex samples (n&#xa0;=&#xa0;1 per group) to assess feasibility and biological plausibility. In non-brain injury dogs, blood mtDNA-CN ranged from 98 to 288 copies per nuclear genome (mean 193&#xa0;&#xb1;&#xa0;72), while values in brain-injured cases ranged from 163 to 228 copies per genome (mean 200&#xa0;&#xb1;&#xa0;33). Cerebral cortex samples exhibited higher mtDNA-CN than blood, consistent with known tissue-specific mitochondrial enrichment. In a single brain-injured case with serial sampling, mtDNA-CN increased over five days. This study presents a validated assay and pilot data for mtDNA-CN quantification in canine samples. While not powered for biomarker evaluation, this method may enable future studies of mitochondrial dynamics in canine brain injury and metabolic disease.

Animals

Psychological skills training for sport-related outcomes: An umbrella review of evidence credibility and methodological quality.

Psychological skills training (PST) is widely used in sport, but review-level evidence remains fragmented across interventions, populations, outcomes, and methodological standards. This umbrella review synthesized evidence on PST-related interventions for sport-related outcomes, including athletic performance, psychological outcomes, cognitive performance, and sports injury, and evaluated evidence credibility, certainty, and methodological quality. A systematic literature search was conducted on 21 May 2025 in MEDLINE, PsycInfo, PubMed, Scopus, SportDiscus, Web of Science, and CINAHL Complete. Overall, 61 reviews involving 42,106 participants were included; 35 meta-analyses involving 28,076 participants were eligible for quantitative synthesis, and 26 reviews or meta-analyses involving 14,030 participants were summarized qualitatively. Quantitative findings showed generally positive point estimates for mindfulness-based interventions, imagery practice, music-based interventions, neurofeedback, perceptual-cognitive training, and multiple PST interventions, but most findings were weak or non-significant and certainty was generally very low. Qualitative evidence suggested potential benefits, but conclusions varied according to intervention definition, delivery, outcome measurement, and methodological quality. Evidence was more developed for athletic performance and psychological outcomes than for cognitive performance and sports injury. Overall, PST-related interventions may benefit sport-related outcomes, but conclusions should remain cautious because of low certainty, methodological heterogeneity, and limited evidence credibility.

Humans

Which radiographic plane should be used to quantify the distal tibia angle on weightbearing CT images?

BACKGROUND: Precise quantification of distal tibial alignment is essential for planning corrective osteotomies and ankle joint replacement surgery. The lateral distal tibial angle (LDTA) is the principal radiographic parameter used for this purpose. While LDTA is increasingly measured on weightbearing cone-beam CT (WBCT) using two-dimensional coronal slices, the optimal measurement plane remains unclear. METHODS: In this retrospective comparative study, full-leg WBCT scans of patients scheduled for supramalleolar osteotomy (n&#x202f;=&#x202f;20; mean age 47&#x202f;&#xb1;&#x202f;12.8 years) were analyzed. LDTA was measured on three coronal planes of the distal tibial plafond (anterior edge, mid-dome, posterior edge) and compared with semi-automated three-dimensional (3D) tibial alignment measurements as the reference standard. RESULTS: Mid-dome LDTA showed no significant difference from the 3D reference (p&#x202f;>&#x202f;0.05) and demonstrated excellent agreement. Anterior measurements significantly overestimated LDTA, while posterior measurements underestimated it (both p&#x202f;<&#x202f;0.05), with only fair agreement. CONCLUSION: LDTA should be measured at the mid-dome of the distal tibial plafond on WBCT to ensure accurate and reproducible alignment assessment. LEVEL OF EVIDENCE: Level III - Retrospective Comparative Study.

Humans

Treating neurogenic detrusor overactivity in order to manage autonomic dysreflexia - A systematic review.

INTRODUCTION: Autonomic dysreflexia (AD) is a severe and potentially life-threatening complication of a spinal cord injury (SCI), particularly in patients with lesions at or above the sixth thoracic level. Neurogenic detrusor overactivity (NDO) is one of the main triggering factors. The impact of NDO treatment on AD remains insufficiently clarified. METHODS: We conducted a systematic review of the literature in PubMed and Cochrane Database between January 1990 and May 2025. Eligible studies included patients with SCI and AD undergoing treatment for NDO, including antimuscarinics, botulinum toxin (BTX) or augmentation cystoplasty. The primary outcome was the assessment of systolic blood pressure (SBP) parameters in patients undergoing cystomanometry. RESULTS: Of the thirteen eligible studies, only five were included. No study evaluated augmentation cystoplasty. One study (12 patients) evaluating fesoterodine and four studies (95 patients) evaluating BTX injection demonstrated improved urodynamic parameters and a decrease in severity of AD during urodynamic studies and in daily life. Improvements in AD-HR-QoL and I-QoL scores were also demonstrated. DISCUSSION: Controlling NDO with fesoterodine or BTX injection reduces the prevalence and severity of AD, likely by limiting abnormal C-fiber recruitment and reducing neurogenic inflammation. BTX additionally modulates TRPV1-expressing afferents, which further reduces AD risk. Although hypertensive peaks improve, submaximal parameters remain unchanged, highlighting the need for additional complementary strategies. CONCLUSION: The use of BTX and fesoterodine for NDO treatment effectively reduces AD episodes in patients with SCI. Further long-term studies are needed to confirm the cardiovascular benefits and inform future therapeutic strategies.

Humans

Comparative safety and operative efficiency of surgical approaches for open reduction and internal fixation of mandibular condylar fractures: a systematic review and network meta-analysis.

BACKGROUND: The optimal surgical approach for mandibular condyle fractures remains controversial, particularly regarding the trade-off between facial nerve safety and surgical efficiency. METHODS: Our systematic review and frequentist NMA analyzed studies evaluating open reduction and internal fixation (ORIF) for mandibular condyle fractures. The primary safety outcome was transient or persistent (&#x2265;6 months) facial nerve weakness. The efficiency outcome was operative exposure time. Surgical approaches were categorized, and random-effects NMAs estimated odds ratios (ORs) and mean differences (MDs). Treatments were ranked using P-scores, and clustered rankings explored safety-efficiency relationships. RESULTS: Overall, 121 studies (n&#x202f;=&#x202f;6659 patients) were included. For facial nerve safety, endoscope-assisted (EA), preauricular transmasseteric anteroparotid (PATMA), and high submandibular (HSMA) approaches ranked highest, while the retromandibular transparotid (RMTA) approach carried a higher risk. Analyses restricted to persistent weakness yielded consistent results. For exposure time, submandibular (SM), HSMA, and retromandibular transmasseteric anteroparotid (RMTMA) approaches were most efficient. Clustered ranking analysis identified HSMA and RMTMA as achieving the best overall balance between safety and efficiency. Subgroup analyses confirmed the overall hierarchy, though evidence for high-level and intracapsular fractures remains limited. CONCLUSIONS: HSMA and RMTMA offer an optimal compromise between safety and efficiency for extracapsular condylar fractures, while EA may minimize nerve injury risk where technical expertise allows. High-quality comparative trials - particularly for intracapsular fractures - are warranted.

Humans

The effect of hip abductor or external rotator strength on dynamic knee valgus in healthy subjects-a systematic review with partial meta-analysis.

BACKGROUND: Weak hip abductors and external rotators (ER) have long been suggested to cause increased dynamic knee valgus. Patients are often prescribed strengthening of these muscles with the expectation that it will reduce their risk of pain and injury. The validity of this claim remains unclear. METHOD: We conducted a systematic review and partial meta-analysis assessing the association between hip strength and knee valgus in healthy subjects. An online search was conducted in May 2026. Databases included Medline, EMBASE, CINAHL and Google Scholar. INCLUSION CRITERIA: English language, asymptomatic subjects, dynamometric hip strength, single or multi-camera kinematic analysis, and statistical tests of difference or correlations between hip abductor or ER strength and dynamic valgus. Data were extracted concerning study design, subject characteristics, relevant outcome measures and statistics. RESULTS: 22 papers qualified for inclusion. Hip abductor correlations: 12 papers found no significant correlation, 2 supported the hypothesis and 2 found evidence contrary. Hip ER correlations: 8 papers found no significant correlation, 2 supported the hypothesis and 2 were contrary. Group differences for hip abduction strength: 3 papers found no difference, 2 found significant differences in support of the hypothesis, 1 found significant difference to contrary. Group differences for ER strength: 1 paper found no significant difference. None of the partial meta-analyses achieved statistical significance. CONCLUSION: Weakness in hip abductors or external rotators may not result in increased dynamic knee valgus in healthy subjects. While continued research may further illuminate our understanding, we discuss alternative explanations.

Humans

Sex-dependent protective effects of microglial tumor necrosis factor on post-stroke inflammation and myelin injury.

Tumor necrosis factor (TNF) is rapidly induced after ischemic stroke, but its proposed cell-specific and sex-dependent functions during post-stroke inflammation remain insufficiently understood. Here, we investigated the role of microglia-derived TNF in the acute and subacute response to permanent middle cerebral artery occlusion (pMCAO). Tnf expression was transiently upregulated after stroke, becoming significant at 4&#xa0;h, peaking at 12-24&#xa0;h, and returning to baseline by 5&#xa0;days. In situ hybridization confirmed strong Tnf expression in the infarct and peri-infarct regions. Whole-brain transcriptomic profiling showed that global TNF deficiency reshaped the early post-ischemic response, shifting it from microglia-associated phagocytic and wound-healing pathways toward an interferon-related inflammatory signature. To define the specific contribution of microglial TNF, we used inducible Cx3cr1CreER:Tnffl/fl mice. Microglial TNF deletion had no effect on infarct volume in males at 24&#xa0;h or 5&#xa0;days after pMCAO, but significantly increased infarct size in females at both time points. In both sexes, brain TNF levels peaked at 24&#xa0;h and were significantly reduced in Cx3cr1CreER:Tnffl/fl mice, confirming microglia as a major source of early post-ischemic TNF. However, downstream consequences diverged by sex. At 5&#xa0;days, male Cx3cr1CreER:Tnffl/fl mice showed reduced microglial reactivity and 18&#xa0;kDa translocator protein (TSPO) signal, with no change in T-cell infiltration, and exhibited increased density of mature oligodendrocytes. In contrast, female Cx3cr1CreER:Tnffl/fl mice displayed enhanced microglial reactivity, increased TSPO binding, higher peri-infarct T-cell infiltration, and reduced oligodendrocyte density and myelin integrity. Together, these findings identify microglial TNF as a sex-dependent regulator of post-stroke inflammation and myelin injury.

Animals

Weight-bearing locomotion mitigates the progression of post-traumatic knee osteoarthritis in male rodents: A systematic review and meta-analysis.

OBJECTIVE: Although knee post-traumatic osteoarthritis (PTOA) has been associated with altered loading, how weight-bearing (WB) activities should be modulated post-injury to preserve knee health remains unknown. This systematic review and meta-analysis examined the effects of WB locomotion on knee PTOA in rodents to provide insight into potential clinical implications. DESIGN: Studies published in PubMed, Cochrane Library, Embase, and CINAHL through 02/2025 and meeting the following criteria were included: 1) rodents with knee PTOA, 2) compared locomotor exercises (treadmill/wheel) to no exercise, 3) outcome measures of PTOA (OARSI/Mankin OA scores, bone quality, osteophyte condition, cartilage quality/morphology). If significant heterogeneity across studies was observed, locomotion speed, time/number of intervention sessions, frequency and duration of intervention, exercise initiation, follow-up time, animal species, PTOA model were analyzed as potential moderator variables that may influence findings. RESULTS: Twenty-two studies met the criteria, resulting in a total of 156 effect sizes (ESs) for meta-analysis (all males). A positive ES denotes less PTOA. Based on the CAMARADES checklist, 5 studies were ranked low risk of bias and 14 studies were ranked moderate risk of bias. Locomotion significantly reduced PTOA severity evaluated using OARSI/Mankin scores (ES=0.927, 95% CI: [0.590, 1.264]) and improved bone quality (ES=0.379, 95% CI: [-0.023, 0.780]) with substantial heterogeneity across studies. Follow-up analyses indicated that greater ESs for reducing OA scores were associated with a shorter duration of each training session, more training sessions, longer intervention duration, and longer follow-up time (all P&#x2264;0.004). Greater ESs for improving bone quality were associated with a longer follow-up time and later exercise initiation post-injury (both P&#x2264;0.014). Locomotion resulted in small to moderate but non-significant positive effects for isolated measures assessing osteophyte condition (ES=0.379, 95% CI: [-0.023, 0.780]), cartilage quality (ES=0.430, 95% CI: [-0.034, 0.893]), and cartilage morphology (ES=0.464, 95% CI: [-0.006, 0.934]). CONCLUSION: WB locomotion reduced the overall degree of knee PTOA in male rodents. Composite knee OA scores may be more responsive to exercise interventions than isolated cartilage/osteophyte measures. The benefits of locomotion may be more prominent with a longer follow-up time or with exercise protocols consisting of shorter but more individual sessions and longer overall intervention durations.

Animals

Stratified medicine with eplerenone for myocardial infarction or injury and no obstructive coronary arteries: A registry-based basket trial.

BACKGROUND: Myocardial Infarction with No Obstructive Coronary Arteries (MINOCA) or Nonischemic Myocardial Injury affects approximately 1 in 9 patients presenting with acute coronary syndrome, yet evidence-based therapies are lacking. Coronary microvascular dysfunction is implicated in the pathogenesis of suspected MINOCA, but its prevalence, prognostic implications and treatment are uncertain. The objectives are, first, to assess the prevalence of coronary microvascular dysfunction in patients with suspected MINOCA and, second, to implement endotype-informed stratified medicine involving patients with coronary microvascular dysfunction to treatment with eplerenone, a cardio- and vasculo-protective mineralocorticoid receptor antagonist. METHODS: This is a prospective, registry-based, multicenter, diagnostic study and nested, randomized, controlled, open-label, blinded-endpoint (PROBE) basket trial. Up to 400 patients with clinically suspected MINOCA and one or more cardiovascular risk factors will be enrolled into a registry-based diagnostic study. Coronary microvascular function will be assessed during invasive angiography using thermodilution. Patients with an index of coronary microvascular resistance (IMR) &#x2265; 25 will be randomized 1:1 to eplerenone (25-50 mg daily for 6 months) or standard care without eplerenone (control group) (n = 150 randomized). Final endotypes will be centrally adjudicated by a panel of blinded cardiologists. The primary outcome of the diagnostic study is the proportion of patients with IMR &#x2265; 25 during index coronary angiography. Secondary outcomes include coronary flow reserve, cardiovascular MRI parameters, patient-reported outcome measures, biomarkers of myocardial fibrosis and vascular inflammation, health outcomes and health economic assessments. The primary outcome of the randomized trial is the within-individual change in NT-proBNP at baseline, 1 month, and 6 months, based on intention-to-treat. Secondary outcomes include mechanistic blood biomarkers and patient-reported outcome measures. VALUE: This registry-based randomized trial will provide novel evidence on endotype-informed secondary prevention therapy with eplerenone for suspected MINOCA.

Humans

Open repairs with biceps rerouting does not impact retears in large to massive rotator cuff tears compared to conventional open repair: a randomized clinical trial.

BACKGROUND: The treatment of large to massive rotator cuff tears leads to a high failure rate and several techniques have been proposed to improve these results. Rerouting the long head of the biceps tendon (LHBT) appears to be a biological reinforcement to increase tendon healing. Therefore, this study aimed to compare the clinical and radiological outcomes of open repair for large and massive rotator cuff tears reinforced with the LHBT to conventional open repair. METHODS: A prospective randomized study was conducted with patients diagnosed with large to massive rotator posterosuperior rotator cuff tear and intact LHBT, randomized into 2 groups: biceps rerouting and conventional open repair. The functional outcomes were assessed by the American Shoulder and Elbow Surgeon score, University of California at Los Angeles score, and SF-12 questionnaire preoperatively and at 6, 12, and 24 months postoperatively. Pain level was also assessed by the visual analog scale including the first day and 2 weeks postoperatively. Structural outcomes were rotator cuff and LHBT healing with magnetic resonance imaging and acromiohumeral distance (AHD) through radiography. RESULTS: We evaluated 58 patients, 29 in each group. At the end of the follow-up there were no statistically significant differences between groups in American Shoulder and Elbow Surgeon (76.1 vs. 80.4, P = .761), University of California at Los Angeles (27.1 vs. 29.1, P = .634), or visual analog scale scores (1.3 vs. 1.1, P = .781). Additionally, rotator cuff healing rates (48.3% vs. 44.8%, P = .402) and LHBT healing rates (79.3% vs. 82.7%, P = .738) were similar. AHD increased in both groups, with no significant difference in delta AHD (P = .513). Both groups showed significant clinical improvement over time in all evaluated outcomes (P < 0,01). No postoperative complications were reported. CONCLUSIONS: We could not identify an advantage of open repair with LHBT rerouting as reinforcement over conventional open repair. Nonetheless, all clinical scores improved at the end of the 24 months of follow-up in both groups.

Humans

Retrosigmoid craniotomy surgical guide: The way forward for precise exposure of the transverse-sigmoid sinuses.

INTRODUCTION: The retrosigmoid craniotomy is the workhorse approach to the cerebellopontine angle. Accurate localisation of the transverse-sigmoid junction (TSJ) is key for optimised exposure and cerebellar retraction. Various methods, both anatomical and navigational, have been used but with suboptimal results. We utilised a 3D-printed retrosigmoid surgical guide in an attempt to overcome this and report our early outcomes and experiences in the design, production and utilisation of the guide. METHODS: This is a prospective cohort study of the patients with retrosigmoid craniotomies performed using the surgical guides. Patient demographics and diagnoses, along with the accuracy of the planned burrhole and craniotomy, need for craniotomy extension, presence of venous sinus injury, set-up time, and cost were reported. RESULTS: There were ten cerebellopontine angle cases in which the surgical guides were utilised, three petrous meningiomas, two trigeminal neuralgias, two metastasis, and three other tumours. The planned burrhole and craniotomy were precise in all cases with accurate exposure of the TSJ and no requirement for craniotomy extension. The mean set up time was 3.9&#xa0;min, and the mean cost of the surgical guides was USD 470.90. One elderly patient had an intraoperative transverse sinus injury related to adherent dura that was planned for exposure. CONCLUSION: The 3D-printed surgical guide is a potential solution to the rapid, precise and consistent identification of the TSJ when performing a retrosigmoid craniotomy. We present our early experience and discuss nuances in the designing, production, and intraoperative phases to optimise the precision of this guide. We suggest two methods to avoid sinus injury in elderly patients: either to plan the craniotomy to the edge of the sinus, or to plan sinus exposure but to use burr drills rather than the osteotome, as in our case, to expose the sinus.

Humans

Proteomic analysis of cisplatin-induced spermatogenesis defects in mice.

BACKGROUND: Cisplatin is a crucial chemotherapeutic agent used for treating various cancers; however, its excessive use can cause irreversible damage to the reproductive system, and the protein expression profile of cisplatin-induced testicular injury remains unclear. METHODS: Male C57BL/6 mice were treated with cisplatin at various doses, and testes were collected for histological, immunofluorescence, and proteomic analyses. Germ cell loss and apoptosis were assessed using H&E staining, TUNEL assays, and immunofluorescence for LIN28A, SYCP3, MVH, and CDK1. Label-free quantitative proteomics identified differentially expressed proteins, which were analyzed for functional enrichment and protein-protein interactions. RESULTS: We observed that cisplatin treatment led to smaller testes, reduced sperm count, and a significant decrease in the number of spermatocytes and spermatids in mice. Label-free quantitative proteomic analysis revealed that cisplatin significantly reduced the expression of cyclin-dependent kinase 1 (CDK1), a key spermatogenesis regulator, in the testes. Reduction in CDK1 expression is correlated with spermatogenic arrest, particularly in spermatocytes. CONCLUSION: These findings highlight the critical role of CDK1 in cisplatin-induced spermatogenic dysfunction and provide new insights into fertility preservation strategies for patients with cancer undergoing chemotherapy.

Animals

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans