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Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial.

BACKGROUND: Patients undergoing acoustic neuroma (AN) surgery often experience&#xa0;postoperative negative emotions, including anxiety, depression, and immune function suppression. This trial evaluated whether perioperative sub-anesthetic esketamine improves early postoperative negative emotions and immune function. METHODS: In this single-center, double-blind, randomized trial, 84 patients scheduled for AN surgery were assigned to esketamine (n = 42) or placebo (n = 42). The esketamine cohort received a continuous intravenous infusion of esketamine at 0.2&#x2009;mg&#xb7;kg-1&#xb7;h-1 during anesthesia, followed by 1&#x2009;mg&#xb7;kg-1 esketamine as an adjuvant in patient-controlled intravenous analgesia (PCIA). The placebo group received saline. The primary outcome was the incidence of depression on postoperative day (POD1), defined as a Hospital Anxiety and Depression Scale-Depression subscale (HADS-D) score > 7. RESULTS: Seventy-seven patients completed the study (39 in the esketamine group, 38 in the placebo group). Esketamine significantly reduced the incidence of depression at POD1 (7.7% versus 31.6%; relative risk 0.24, 95% CI: 0.08-0.80, p&#x2009;=&#x2009;0.008) and POD3 (0.0% versus 15.8%, relative risk 0.00, 95% CI: 0.00-0.47, p&#x2009;=&#x2009;0.031) compared with placebo. The incidences of anxiety on POD1 and 3 and sleep disturbances on POD1 were also significantly reduced (p&#x2009;<&#x2009;0.05). Notably, no significant differences were observed between the two groups in terms of immune function, postoperative pain scores, or intraoperative morphine equivalent. Adverse events did not differ between the groups. CONCLUSION: Perioperative sub-anesthetic esketamine reduced postoperative depression and anxiety, and improve sleep quality after AN surgery, without significant effects on early immune function or acute postoperative analgesia. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400084537.

Humans

Effect of photobiomodulation on pain relief and functional improvement in fractures: a systematic review and meta-analysis.

INTRODUCTION: Fractures, the most common type of trauma, can cause considerable distress to patients. Pain can not only affect the comfort of fracture patients but also delay their participation in rehabilitation training. Photobiomodulation (PBM) has been associated with pain reduction and the promotion of tissue healing. This systematic review and meta-analysis aimed to evaluate the efficacy of PBM in reducing pain and promoting rehabilitation in patients with fractures. METHODS: This study was registered on PROSPERO (CRD42024591373). We systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science for RCTs that investigated PBM in fractures as of August 2025. The primary outcome was the pain score. The secondary outcomes included functional and healing. RESULT: Finally, 12 and 9 studies were ultimately included in the systematic review and meta-analysis, respectively. The pooled analysis showed that the one-week pain score was lower in the PBM group than in the placebo group (MD -0.74, 95% CI -1.00, -0.47, p&#x2009;<&#x2009;0.0001, I2 = 0%). Subgroup analysis showed that the difference between the two groups was statistically significant regardless of fracture site or acupoint irradiation. Changes in pain scores were statistically significant in both groups at different wavelength combinations. The improvement in grip strength at 4&#x2009;weeks was significantly greater in PBM than in placebo (MD 5.03, 95% CI 4.29, 5.78; p&#x2009;<&#x2009;0.0001; I2 = 0%). There were no significant differences in pain and functional scores at 4-26&#x2009;weeks. Bone healing did not show differences between the two groups. No side effects reported. CONCLUSION: PBM appears to relieve short-term pain in fractures and improve grip strength in patients with upper limb fractures, but does not show significant long-term benefits. Evidence for mandibular functional recovery and bone healing remains inconsistent. Future studies should determine therapeutic parameters and their impact on bone healing and long-term functional outcomes across fracture types.

Humans

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale &#x2265;3.0, n&#x202f;=&#x202f;12) and controls (n&#x202f;=&#x202f;10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p&#x202f;=&#x202f;0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p&#x202f;<&#x202f;0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p&#x202f;<&#x202f;0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans

Endovascular thrombectomy versus best medical therapy for acute vertebrobasilar artery occlusion in patients with low NIHSS scores: a&#xa0;meta-analysis.

OBJECTIVE: The efficacy of endovascular thrombectomy (EVT) for acute vertebrobasilar artery occlusion (VBAO) presenting with mild symptoms (National Institutes of Health Stroke Scale [NIHSS] score &#x2264;10) remains uncertain. This meta-analysis aimed to compare the effectiveness and safety of EVT versus best medical therapy (BMT) in this population. METHODS: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2025 for comparative studies. The primary outcome was 90-day excellent functional outcome (modified Rankin Scale [mRS] score 0-1). Secondary outcomes included functional independence (mRS 0-2), symptomatic intracranial hemorrhage (sICH), and all-cause mortality. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. RESULTS: Seven observational studies involving 3,107 patients were included. In unadjusted analyses, EVT was associated with a higher rate of excellent functional outcome (OR 2.17; 95% CI 1.58-2.96) but not with functional independence (OR 1.58; 95% CI 0.90-2.77). After adjustment for confounders, EVT was associated with higher rate of excellent functional outcome (OR 2.86; 95% CI 1.89-4.31) and functional independence (OR 1.91; 95% CI 1.01-3.62). Safety outcomes including sICH and mortality did not differ significantly between groups. CONCLUSION: In patients with acute VBAO and mild symptoms, EVT may be associated with superior functional outcomes compared to BMT alone, without a significant increase in procedural risks. These findings suggest a potential role for EVT in selected patients with low NIHSS scores and underscore the need for confirmation in randomized trials.

Humans

Game changer? Cognitive-motor effects of VR exergaming compared to video-based training.

BACKGROUND/OBJECTIVE: Virtual reality (VR) exergaming enhances several cognitive domains through multisensory engagement. Acute cognitive benefits of VR are established, but evidence for direct comparisons with non-immersive controls is limited. This study aimed to determine whether VR exercise provides additional cognitive and cognitive-motor benefits beyond a matched non-immersive active stick-fight video (SFV) intervention, and whether effects persist after training. METHODS: In this randomized quasi-experimental study, N&#x2009;=&#x2009;55 healthy adults (VR: n&#x2009;=&#x2009;30; SFV: n&#x2009;=&#x2009;25; 25.5&#x2009;&#xb1;&#x2009;7.1&#x2009;years; 41.8% female) completed an 8-week program (2&#x2009;&#xd7;&#x2009;30&#x2009;min/week), of VR or SFV matched in movement patterns, frequency, intensity and duration. Measurements included reaction time (RT), Stroop Test (versions 1-3), Letter Cancellation Test (LCT), Trail Making Test (TMT), Trail Walking Test (TWT) and Fitts task (difficulty level 1-4). Data were analyzed using mixed-design ANOVAs. RESULTS: Improvements were observed in Stroop reading (F(1,53) = 14.84, p < .001, &#x3b7;2 = 0.219), Stroop inhibition (F(1,53) = 10.99, p = .002, &#x3b7;2 = 0.172), and LCT (F(1,53) = 4.57, p = .037, &#x3b7;2 = 0.079). A time&#x2009;&#xd7;&#x2009;group interaction was found for TMT (F(1,53) = 6.55, p = .031, &#x3b7;2 = 0.110), indicating greater changes following VR training. Both groups improved cognitive-motor performance (TWT: F(1,25) = 55.32, p < .001, &#x3b7;2 = 0.689; Fitts3: F(1,53) = 44.97, p < .001, &#x3b7;2 = 0.459), with greater gains for VR in Fitts3 (p = .006). CONCLUSION(S): Eight weeks of VR and SFV enhanced cognitive and cognitive-motor performance. VR provided domain-specific advantages in executive function, but these effects were not uniformly persistent. SFV sustained more improvements in real-world-relevant cognitive-motor tasks.

Humans

Craniotomy versus Endoscopic Membranectomy in the Treatment of Non-Homogeneous Chronic Subdural Hematoma: A Pilot Randomized Parallel-Group Active-Controlled Trial (EMiT CSDH 2).

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition with persistent challenges related to recurrence. Endoscopic membranectomy (EM) has shown promising results in managing symptomatic non-homogenous (SNH)-CSDH, but comparative evidence against craniotomy with membranectomy (CM) is lacking. OBJECTIVES: To compare the safety and efficacy of EM versus CM in managing SNH-CSDH. MATERIALS AND METHODS: A pilot randomized parallel-group active-controlled open- labeled superiority trial from September 2023 to November 2024 at Government Kilpauk Medical College, Chennai, India. Sixty patients with SNH-CSDH were randomized into EM and CM groups. Recurrence was the primary outcome. Secondary outcomes included operative time, complications, radiological indices, pain, hospital stay, and functional recovery. All patients were followed for six months. RESULTS: No recurrence was observed in either group at six months. Two CM patients required reoperation on postoperative day one ( P = 0.15). EM was associated with shorter operative time ( P = 0.02), lower incidence of post-operative subdural residual fluid ( P = 0.015), better early hematoma reduction/subdural space reduction index ( P = 0.008), midline shift/symmetry improvement index ( P = 0.001), and lesser surgical site swelling ( P < 0.001). All patients were ambulant and had a Glasgow coma scale (GCS) 15 at discharge and at six months (including reoperated patients). Pain scores and functional recovery were comparable. EM patients had shorter hospital stays ( P = 0.004) and no significant complications. CONCLUSION: EM demonstrated favorable early radiological outcomes, fewer complications, and comparable functional recovery and recurrence versus CM in SNH-CSDH. Independent reproduction and larger multicentric trials are needed for validity and generalizability.

Humans

Impact on analgesia, diaphragmatic function, and recovery between erector spinae plane block versus superior trunk block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Effective analgesia and preservation of diaphragmatic function are key considerations in analgesia for shoulder surgery. The superior trunk block provides analgesia with reduced phrenic nerve involvement, while the erector spinae plane block offers minimal impact on diaphragm motion. This randomized controlled trial compared the analgesic efficacy, impact on diaphragmatic motion, and postoperative recovery between the two blocks. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomized to receive either erector spinae plane block or superior trunk block. Primary outcomes were postoperative VAS and changes in diaphragmatic excursion. Secondary outcomes included Quality of Recovery-15 (QoR-15) scores, morphine-equivalent consumption, and the handgrip strength motor blockade. RESULTS: The superior trunk block resulted in significantly lower dynamic VAS at 1-h postoperatively (0.1 [0.0, 0.2] vs. 5.7 [4.0, 7.6]; p&#x2009;<&#x2009;0.001) and reduced 24-h morphine consumption (7.8 [2.5, 15.0] mg vs. 12.7 [7.5, 17.3] mg; p&#x2009;=&#x2009;0.038) compared to the erector spinae plane block. However, diaphragmatic excursion was better preserved in the erector spinae plane block group (8.37% &#xb1; 20.7% vs. -20.09% &#xb1; 22.2%; p&#x2009;<&#x2009;0.001), with a lower incidence of partial hemidiaphragm paresis (3.3% vs. 46.7%; p&#x2009;<&#x2009;0.001). At 24&#x2009;h postoperatively, QoR-15 scores were higher in the superior trunk block group (p&#x2009;=&#x2009;0.047), and no patient in either group developed handgrip motor blockade. CONCLUSIONS: Superior trunk block offers superior early postoperative analgesia and better overall recovery, while erector spinae plane block minimizes diaphragmatic impairment. However, the erector spinae plane block may represent an option only in carefully selected patients at high respiratory risk, acknowledging its significantly poorer early analgesic profile.

Humans

Unraveling the c-Myc-CASC19/HDAC1-NPM1 epigenetic axis: A novel regulatory circuitry and therapeutic target in gastric carcinogenesis.

Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation.

Humans

Integrated widely targeted metabolomics and GC-IMS reveal dynamic flavor, nutritional, functional, and metabolic profiles in macadamia kernels during processing.

Different processing stages influence the color, flavor, and antioxidant activities of macadamia kernels. However, the biochemical mechanisms that occur during processing are not well known. This study integrated widely targeted metabolomics (UPLC-MS/MS) with GC-IMS to systematically characterize non-volatile and volatile compounds in macadamia kernels across key three sample groups: fresh kernels (FMN), low-temperature-dried kernels (DMN), and roasted kernels (BMN). A total of 622 non-volatile metabolites and 52 volatile compounds were identified. Low-temperature drying promoted the accumulation of phenolic acids and flavonoids, enhancing antioxidant capacity. Roasting degraded heat-sensitive nutrients but generated flavor compounds via Maillard reaction and lipid oxidation, shifting aroma from green to nutty notes. Nutritional assessment confirmed that roasting significantly reduced antioxidant activities and bile acid binding capacity. Pearson correlation analysis verified the key metabolite-antioxidant relationships. These findings provide critical insights into metabolic dynamics during nut processing and establish a scientific basis for optimizing thermal processing strategies.

Metabolomics

Pharmacological and non-pharmacological modulation of striatal dopamine release: a meta-analysis of [11C]raclopride PET studies.

The dopaminergic system has long been a central focus of functional neuroimaging. Positron emission tomography (PET) with the D2/D3 receptor radioligand [11C]raclopride remains the most widely used method for indirectly quantifying striatal dopamine release in vivo. However, no previous meta-analysis has studied the relative magnitude and regional distribution of dopamine release across different interventions or cognitive interventions overall. To address this gap, in this meta-analysis of 92 [11C]raclopride PET studies (n&#x2009;=&#x2009;1640), we compared the magnitude and regional distribution of dopamine release induced by amphetamine, methylphenidate, ketamine, alcohol, and cognitive challenges with and without reward. Amphetamine induced approximately four-fold greater dopamine release than cognitive challenges (10.9 vs. 2.7%, p&#x2009;<&#x2009;0.001), and approximately twice that of alcohol (4.8%, p&#x2009;<&#x2009;0.001), with effects comparable to methylphenidate (11.5%) and slightly greater than ketamine (9.8%). Psychostimulant-induced increase in synaptic dopamine was greater in putamen and ventral striatum than in caudate, whereas alcohol preferentially engaged ventral striatum. Dopamine release did not differ between rewarded and non-rewarded cognitive tasks in the ventral striatum (p&#x2009;>&#x2009;0.14) or overall striatum (p&#x2009;>&#x2009;0.10). Methylphenidate-induced increases in synaptic dopamine appeared to attenuate with advancing age, whereas cognitive challenges were associated with greater dopamine release in older individuals. These findings demonstrate that individual pharmacological and cognitive interventions differ markedly in both magnitude and regional pattern of dopamine release. They also suggest that [&#xb9;&#xb9;C]raclopride PET may have limited sensitivity for distinguishing reward-related from non-reward-related dopamine release. These findings have implications for the design and interpretation of future neuroimaging studies of dopaminergic function in health and disease.

Journal Article

Uce-based phylogeny and classification of Megachilini.

The generic-level classification of the bee tribe Megachilini (Megachilidae) has remained controversial due to poor phylogenetic resolution at the base of the group, particularly among the brood parasitic genera and the numerous dauber ("Chalicodoma s. l.") lineages. We present a phylogenomic analysis of Megachilini based on ultraconserved elements (UCEs), sampling 52 ingroup taxa with emphasis on the dauber lineages. We also present a combined UCE&#xa0;+&#xa0;six-gene analysis to improve taxon coverage, resulting in a dataset with 127 ingroup taxa. Maximum likelihood, coalescent, and Bayesian analyses of multiple UCE matrices recover largely congruent topologies with substantially improved support relative to previous studies. Our results strongly support the monophyly of Megachilini, the early divergence of Noteriades and Gronoceras, and a single origin of brood parasitism. All remaining non-parasitic Megachilini form a moderately supported clade sister to the brood parasitic lineage. The leafcutter bees are monophyletic and nested within dauber lineages. Several major dauber clades are consistently recovered, including an exclusively Australian clade corresponding to the Hackeriapis group of subgenera, while several recognized subgenera are paraphyletic. The lineage known as Morphella, previously placed in synonymy with the subgenus Callomegachile, was not closely related to that subgenus and is here treated as a valid subgenus. Divergence-time analyses place the crown age of Megachilini in the late Eocene to early Oligocene, with major extant lineages diversifying during the Miocene. Limited morphological diagnosability of several clades indicates that splitting non-parasitic lineages into numerous genera would result in an impractical classification that would widen the gap between taxonomists and non-specialists and exacerbate the taxonomic impediment in bees. We therefore advocate retaining a single genus Megachile for non-parasitic Megachilini (excluding Noteriades and Gronoceras), as the classification best supported by phylogenomic evidence and most robust to future taxon sampling.

Animals

Clinical performance evaluation of single-shade versus multi-shade composite resins in non-carious cervical lesions: a 36-month randomized clinical trial.

BACKGROUND: Composite resins are widely used as the material of choice for definitive restorations due to their ability to integrate functional and aesthetic aspects in dental rehabilitation. Recently, one-shade composite resins have been introduced to simplify the clinical workflow. OBJECTIVES: This study aimed to compare the clinical performance of a "chameleon effect" composite resin with that of a multi-shade composite resin in non-carious cervical lesions after 36 months of follow-up. METHODS: This study was a randomized, controlled, double-blind clinical trial with an equivalence design using a split-mouth approach. The sample consisted of 60 patients presenting at least two non-carious cervical lesions, totaling 120 restorations. Restorations were performed using two materials from the same commercial brand: Vittra Unique (one-shade group) and Vittra APS (multi-shade group). The clinical performance of the restorations was longitudinally evaluated according to the FDI criteria. Survival analysis was performed using Kaplan-Meier curves and the log-rank test, while other clinical parameters were compared using the chi-square test (&#x3b1; = 0.05). RESULTS: At baseline, no statistically significant differences were observed between the groups regarding the evaluated biological, functional, and aesthetic parameters (p > 0.05). Both materials demonstrated clinically acceptable performance according to the FDI criteria, with no significant differences between them. CONCLUSIONS: After 36 months, no significant differences were observed between the one-shade and the multi-shade composite resins in the restoration of non-carious cervical lesions. CLINICAL SIGNIFICANCE: This 36-month randomized clinical trial demonstrates that single-shade composite resins achieve structural durability and aesthetic integration equivalent to traditional multi-shade layering when restoring non-carious cervical lesions. This evidence validates a simplified, single-shade restorative workflow, significantly reducing chairside time and operator-dependent variables without compromising the clinical longevity.

Humans

Desert-derived Ensifer sp. SA403 enhances potato salt tolerance by reshaping rhizosphere microbiome functions and host responses.

Soil salinization increasingly threatens global food security, and potato (Solanum tuberosum L.), a moderately salt-sensitive crop, is particularly vulnerable to saline soils. Plant growth-promoting rhizobacteria (PGPR) offer a promising strategy to improve crop performance, yet how PGPR interact with native microorganisms to enhance potato salt tolerance remains poorly understood. In this study, we identified a desert-derived PGPR strain, Ensifer sp. SA403, which substantially enhanced potato performance under high salinity across sterile, non-sterile and field conditions. Physiologically, inoculation with SA403 reduced shoot Na&#x207a; accumulation and increased the K&#x207a;/Na&#x207a; ratio; notably, these effects were markedly stronger in non-sterile substrates than under sterile conditions, indicating that SA403-mediated ion homeostasis relies on cooperation with the resident microbiota rather than on the strain acting alone. Metagenomic profiling indicated that SA403 strain reshaped rhizosphere communities, significantly enriching beneficial taxa such as Priestia and Bradyrhizobium, and upregulated functional pathways involved in glutathione and sulfur metabolism. Furthermore, host transcriptomic analyses showed that SA403 modulated plant responses to salt stress, with differentially expressed genes enriched in jasmonic acid signaling, ethanolamine metabolism and amino-acid biosynthesis pathways. Field trials on saline soils confirmed that SA403 significantly increased seedling emergence and tuber weight. Together, our results demonstrate that SA403 functions as a biological mediator that optimizes rhizosphere microecology and coordinates ion balance and host signaling to enhance potato salt tolerance. These findings support the potential of SA403 as a robust PGPR-based tool for sustainable potato production on saline soils.

Rhizosphere

Induced degradation of Ufd1 reveals regulation of cohesin by the VCP/p97Ufd1-Npl4 complex.

The AAA ATPase VCP/p97 has emerged as a critical regulator of ubiquitin and chromatin-associated processes but progress in understanding has been hampered by the complexity of p97 functions and the various p97 cofactors involved. Here, we combined ubiquitin profiling with acutely induced degradation of the Ufd1 subunit of the p97 ubiquitin adapter, Ufd1-Npl4, in human cells. We identified a set of chromatin regulators, HUS1, XRCC1, MORF4L1, and the cohesin subunit RAD21 as targets of p97Ufd1-Npl4 We find that RAD21 is ubiquitylated and targeted by p97Ufd1-Npl4 specifically in S phase to remove a subpopulation of cohesin from chromatin. Acute degradation of Ufd1 in S phase, after replication licensing is completed, impedes replication and leads to replication-associated DNA damage. Our findings suggest that a fraction of cohesin rings need to be removed by p97Ufd1-Npl4 from DNA to allow unhindered replication and reveal a critical function of p97 that ensures genome stability.

Cell Cycle Proteins

Recurrence of peripartum cardiomyopathy in subsequent pregnancy stratified by left ventricular function: a systematic review and meta-analysis.

AIMS: Subsequent pregnancy in women with prior peripartum cardiomyopathy (PPCM) carries a risk of relapse and adverse maternal outcomes. This meta-analysis aimed to determine the recurrence of PPCM relapse and associated maternal and foetal outcomes during subsequent pregnancy, stratified by baseline (pre-subsequent pregnancy) left ventricular ejection fraction (LVEF). METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. Nine databases were searched through June 2025 for cohort studies reporting subsequent pregnancy outcomes in women with prior PPCM, stratified as recovered (LVEF &#x2265;50%) or non-recovered (LVEF <50%) groups. Outcomes included PPCM relapse, maternal mortality, LVEF during and after pregnancy, LV recovery, symptom worsening, and obstetric/neonatal events. Risk of bias was assessed with ROBINS-E, and random-effects models were used. RESULTS: Six cohort studies comprising 266 women were included (174 in recovered group and 92 in non-recovered group). Relapse occurred in both groups with no significant difference [rate ratio (RR) 0.77, 95% CI 0.50-1.19; I2 = 3%]. Maternal mortality was significantly lower in the recovered group (1.7% vs 10.9%; RR 0.27, 95% CI 0.09-0.87; I2 = 0%). Recovered group had higher mean LVEF during subsequent pregnancy (mean difference [MD] 17.0; P < .001), higher postpartum LVEF (MD 11.69; P = .005; I2 = 84%), and greater likelihood of LV recovery (RR 2.07; P = .005; I2 = 0%). No significant differences were observed in symptom worsening or obstetric/neonatal outcomes. CONCLUSION: Recovered LVEF prior to subsequent pregnancy is associated with improved maternal outcomes, yet relapse remains common. Left ventricular ejection fraction alone is insufficient for risk stratification, and individualized multidisciplinary care is essential for all women with prior PPCM.

Female

Improved quality of life and prolonged survival with add-on homeopathic treatment in patients with non-small cell lung cancer: a prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study.

BACKGROUND: Alongside conventional anticancer treatment, add-on homeopathy might help to alleviate adverse effects of conventional therapy. AIM: The aim of this study was to replicate previous studies on the effect of adjunctive homeopathy on quality of life (QoL) and survival in non-small cell lung cancer (NSCLC) patients. METHOD: In this prospective, randomized, placebo-controlled, double-blind, three-arm multicenter phase III study with quadruple-checked data analysis, we investigated the potential effects of an add-on homeopathic treatment compared to placebo in patients with stage IV NSCLC in terms of QoL. Ninety-eight received either individualized homeopathic medicinal products (HMPs; n&#x2009;=&#x2009;51) or placebo (n&#x2009;=&#x2009;47) in a double-blinded fashion. Fifty-two control patients without homeopathic treatment were only observed in terms of their survival rate. The ingredients of the various HMPs were mainly prepared of plant, mineral, or animal origin. The data entry and statistical analysis were subject to an exceptional quadruple-checked data analysis process. The analysis presented in this article was inspired by our earlier report of this trial published in The Oncologist in 2020, which was retracted by that journal in November 2025 after two corrections; a majority of the co-authors disagreed with this decision. The present article is based on the same trial dataset but was deliberately designed to highlight the unique research methodology: design and preparation by a lead statistician, data entry, data clearing and independent statistical evaluation were performed in four mutually independent steps, reporting follows the CONSORT statement, and the interpretation of the findings has been reframed conservatively. RESULTS: Global health status (QoL) was higher in the homeopathy group than in the placebo group after 9&#xa0;weeks and after 18&#xa0;weeks (p&#x2009;<&#x2009;0.001). With the exception of cognitive functioning at 9&#xa0;weeks and of pain, diarrhea and financial difficulties at 9&#xa0;weeks, all functional and symptom scales of the EORTC QLQ-C30 favored the homeopathy group (p&#x2009;<&#x2009;0.001 for the multivariate comparisons), with between-group differences exceeding the threshold of 10 points that is generally regarded as clinically meaningful. Median survival time over the 730-day observation period was 435&#xa0;days in the homeopathy group, 257&#xa0;days in the placebo group (p&#x2009;=&#x2009;0.010), and 228&#xa0;days in the non-randomized control group (p&#x2009;<&#x2009;0.001); the corresponding 2-year survival rates were 45.1%, 23.4%, and 13.5% (homeopathy vs. placebo p&#x2009;=&#x2009;0.020; homeopathy vs. control p&#x2009;<&#x2009;0.001). The difference between the placebo group and the non-randomized control group was not statistically significant (p&#x2009;=&#x2009;0.154). CONCLUSION: In this trial, add-on homeopathy was associated with better quality of life across most functional and symptom domains, with clinically meaningful effect sizes congruently to a previous open study. Survival time was significantly longer in the homeopathy group compared to both the placebo and control groups. Independent replication, ideally within contemporary immuno-oncological treatment regimens is required. TRIALS REGISTRATION: ClinicalTrials.gov; No.: NCT01509612; January 7, 2012.

Humans

Efficacy and safety of revascularization in patients with chronic limb-threatening ischemia by kidney function.

BACKGROUND: The optimal revascularization strategy for patients with chronic limb-threatening ischemia (CLTI) with chronic kidney disease (CKD) remains unknown. We evaluated whether the efficacy and safety of surgical vs endovascular revascularization differ by kidney function. METHODS: In this post hoc secondary analysis of BEST-CLI trial (NCT02060630), 1,704 patients with CLTI were stratified by baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m&#xb2;): non-CKD (eGFR &#x2265; 90), mild-moderate CKD (eGFR 45-89), advanced CKD (eGFR < 45 or dialysis). The primary outcome was a composite of major adverse limb events (MALE) or death. We estimated the difference in restricted mean time lost (RMTL, in days) adjusted for inverse probability treatment weights. RESULTS: Surgical revascularization was significantly associated with fewer days with MALE or death in non-CKD (RMTL difference: -127.8 days; 95% CI -176.1, -79.6) and mild-moderate CKD (-63.2 days; 95% CI -104.7, -21.8) but not in advanced CKD (-16.4 days; 95% CI -78.8, 46.0; P interaction = .02). This attenuation reflected a diminishing mortality benefit with more severe CKD (P interaction = .01), whereas the association with fewer days with MALE remained consistent across CKD strata (P interaction = .34). Major adverse cardiovascular events and serious adverse events were more common with more severe CKD but did not differ significantly by treatment. CONCLUSIONS: Surgical vs endovascular revascularization was consistently associated with fewer days with MALE across CKD strata. However, its association with mortality varied by kidney function, attenuating the overall benefit for the composite endpoint of MALE or death. These results support individualized revascularization strategies, but require prospective confirmation. TRIAL REGISTRATION: The BEST CLI trial is registered at ClinicalTrials.gov (NCT02060630).

Humans

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age &#xf0b3;40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans