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Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.

BACKGROUND AND OBJECTIVES: The impact of ischemic extent on the efficacy and safety of intravenous thrombolysis before thrombectomy remains uncertain. The aim of this study was to evaluate whether the baseline ischemic extent, measured by the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), modifies outcomes of intravenous tenecteplase administered before endovascular thrombectomy. METHODS: This was a post hoc analysis of the BRIDGE-TNK (thrombectomy with vs without rhTNK-tPA in stroke) trial, conducted across China from May 2022 to September 2024. We compared the efficacy and safety of intravenous tenecteplase plus thrombectomy vs thrombectomy alone in acute large-vessel occlusion stroke patients within 4.5 hours of last known well, stratified by baseline ASPECTS (<8 vs 8-10). The outcomes included 90-day functional independence (modified Rankin Scale score of 0-2), 48-hour symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Regression models incorporating a treatment-by-ASPECTS interaction term were used for analysis. RESULTS: Among 550 patients, 241 (43.8%) had ASPECTS <8 (median [interquartile range, IQR] age, 69 [61-77] years; 56.4% male) and 309 had ASPECTS 8-10 (median [IQR] age, 70 [61-77] years; 59.5% male). The rate of functional independence was significantly higher in the tenecteplase plus thrombectomy group than in the thrombectomy-alone group in the ASPECTS <8 subgroup (adjusted risk ratio [aRR], 1.67; 95% CI 1.18-2.35), but not in the ASPECTS 8-10 subgroup (aRR, 0.99; 95% CI 0.84-1.17; pinteraction = 0.007). Rates of sICH did not differ significantly between treatment groups in either ASPECTS subgroups (ASPECTS <8: 10.0% vs 11.2%; ASPECTS 8-10: 7.5% vs 2.8%; pinteraction = 0.11). Ninety-day mortality was comparable between treatment groups in the ASPECTS <8 subgroup, but numerically higher with tenecteplase plus thrombectomy in the ASPECTS 8-10 subgroup (aRR = 1.89, 95% CI 0.99-3.61, pinteraction = 0.04). DISCUSSION: In this exploratory post hoc analysis, a signal of benefit was observed in patients with ASPECTS <8 who received intravenous tenecteplase before thrombectomy, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10. Prospective confirmation in randomized trials is required before practice change. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT04733742.

Humans

Oliceridine used for patient-controlled analgesia on postoperative quality of recovery in patients undergoing laparoscopic gynecological tumour resection: a randomized clinical trial.

BACKGROUND: Oliceridine, a novel biased &#x3bc;-opioid receptor agonist, is widely used perioperatively, yet limited data exists regarding its impact on postoperative quality of recovery. This study investigated the effect of oliceridine-based&#xa0;patient-controlled intravenous analgesia (PCIA) on postoperative quality of recovery among patients undergoing laparoscopic gynecological tumour resection. METHODS: Ninety&#x2011;four female patients scheduled for elective laparoscopic gynecological tumour resection were included. Patients were randomized to two groups: oliceridine group (loading dose 1.5&#x2009;mg, PCIA 0.55&#x2009;mg/kg) or sufentanil group (loading dose 10&#x2009;&#x3bc;g, PCIA 3&#x2009;&#x3bc;g/kg). The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1. The secondary outcomes included the QoR-40 score, the numeric rating scale (NRS) pain score, the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) index and adverse events within 3 postoperative days. RESULTS: Higher QoR-40 scores were found in the oliceridine group on postoperative day 1 (182.9&#x2009;&#xb1;&#x2009;3.1 versus 177.5&#x2009;&#xb1;&#x2009;3.9, p&#x2009;<&#x2009;0.001). Compared with the sufentanil group, the oliceridine group showed better QoR-40 scores within 3&#x2009;days after operation. No significant differences were observed in NRS pain scores or HADS-A scores between the two groups (all p&#x2009;>&#x2009;0.05). However, the median FRAIL score in the oliceridine group was lower on postoperative day 2 (p&#x2009;=&#x2009;0.018). CONCLUSION: Oliceridine used in PCIA improves early postoperative recovery quality of patients undergoing laparoscopic gynecological tumour resection. It provides analgesic effect comparable to sufentanil and lowers incidences of postoperative frailty, nausea and vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR.org.cn, identifier: ChiCTR2400094271.

Humans

Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.

AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index &#x2265;27 and &#x2264;35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15&#xb0;C) and ~2.5-fold (moderate, 4&#xb0;C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53&#xa0;&#xd7;&#xa0;RMR in mild and 1.94&#xa0;&#xd7;&#xa0;RMR in moderate cold. In type 2 diabetes, the increase was 1.57&#xa0;&#xd7;&#xa0;RMR and 2.09&#xa0;&#xd7;&#xa0;RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6&#xa0;&#xb1;&#xa0;0.5 mmol/l, p=0.003) and fasting glucose (-0.6&#xa0;&#xb1;&#xa0;0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8&#xa0;&#xb1;&#xa0;10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9&#xa0;&#xb1;&#xa0;12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.

Humans

Impact of renal dysfunction on immediate versus staged revascularization of non-culprit lesions in patients with ST segment elevation myocardial infarction: a pre-specified subgroup analysis of the randomized MULTISTARS AMI trial.

BACKGROUND: Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). METHODS: In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60&#xa0;ml/min/1.73 m2. Patients with an eGFR&#x2009;<&#x2009;30&#xa0;ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1&#xa0;year. RESULTS: In MULTISTARS AMI, 108 (13%) of 832 patients had renal dysfunction. The primary endpoint occurred more frequently in patients with renal dysfunction (19.4% vs. 11.2%, unadjusted HR 1.82, 95% CI 1.13-2.94), primarily driven by higher rates of death. Among patients with renal dysfunction, the rates of the primary end point were 14.5% and 24.5% in the immediate and staged PCI groups (unadjusted HR 0.55, 95% CI 0.23-1.33). There was no interaction between renal dysfunction and the randomized treatment assignment with respect to the primary end point (adjusted HR 1.30, 95% CI 0.8-2.20, pint 0.82). The occurrence of acute renal insufficiency was statistically similar in patients with renal dysfunction who underwent immediate and staged PCI (10.9% vs. 18.9%, unadjusted HR 0.61, 95% CI 0.22-1.72, pint 0.09). Renal dysfunction at baseline emerged as a strong risk factor for the development of acute renal insufficiency (adjusted HR 5.0, 95% CI 2.30-10.70, p&#x2009;<&#x2009;0.01). CONCLUSIONS: Outcomes with immediate compared to staged multivessel PCI did not appear significantly altered by the presence of renal dysfunction&#xa0;at baseline. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275).

Humans

Effects of single-injection vs. continuous brachial plexus blocks for shoulder surgeries on patient-reported outcomes: a systematic review and meta-analysis with trial sequential analysis of randomised controlled trials.

INTRODUCTION: Single-injection and continuous brachial plexus block techniques are used widely for postoperative analgesia in patients undergoing shoulder surgery. Although patient-reported outcomes are described in individual studies, their effects have not been synthesised comprehensively using a patient-centred framework. We sought to compare the effects of single-injection vs. continuous brachial plexus block techniques on patient-reported outcomes in adult patients following elective shoulder surgery. METHODS: Databases were searched from inception to October 2025 and randomised controlled trials reporting patient-reported outcomes were included. Co-primary outcomes were postoperative patient-reported pain intensity at rest and during movement at 12&#x2009;h, 24&#x2009;h and 48&#x2009;h post-surgery. Secondary outcomes included nausea and vomiting; sleep quality; patient satisfaction; opioid requests; and functional scores. Random-effects meta-analysis and trial sequential analysis were performed, with risk of bias and quality of patient-reported outcome reporting assessed. RESULTS: Twenty randomised controlled trials that included 1198 patients were analysed. Continuous brachial plexus blocks were associated with lower pain at rest at 12&#x2009;h, 24&#x2009;h and 48&#x2009;h, with mean differences (MD) of -1.96 (95%CI -2.81 to -1.11, p&#x2009;<&#x2009;0.001), -1.66 (95%CI -2.27 to -1.05, p&#x2009;<&#x2009;0.001) and&#x2009;-&#x2009;1.18 (95%CI -1.84 to -0.53, p&#x2009;<&#x2009;0.001), respectively. Pain on movement could only be pooled at 24&#x2009;h and 48&#x2009;h and showed MD -2.04 (95%CI -4.26-0.19, p&#x2009;=&#x2009;0.07) and&#x2009;-&#x2009;1.30 (95%CI -3.67-1.07, p&#x2009;=&#x2009;0.28) respectively. The co-primary outcomes approached or exceeded the predefined minimal clinically important difference for pain scores after shoulder surgery, in favour of continuous techniques. DISCUSSION: Continuous brachial plexus blocks are associated with better pain at rest and other patient-centred outcomes following shoulder surgery, while effects on dynamic pain and long-term functional recovery remain uncertain.

Humans

The use of diode laser and scalpel blade in stage-two dental implant surgery: a comparative study.

OBJECTIVE: The use of lasers in dental implant procedures raises questions regarding the preservation of keratinized tissues and implant outcomes. This study aimed to compare the clinical effects (pain and impression time) and soft tissue healing (keratinization, peri-implant probing, bleeding, and healing) of diode lasers and scalpels used during stage-two dental implant surgery. METHOD AND MATERIALS: A prospective randomized clinical trial with a 1:1 allocation ratio was conducted. The study included 30 patients, each with a single, fully osseointegrated implant. Patients were categorized into two groups. The study group underwent stage-two implant surgery using a 970-nm diode laser. In the control group, implants were exposed using a conventional surgical blade. A comparison between the diode laser and conventional scalpel groups was made based on clinical outcomes (pain and impression time) and soft tissue healing (keratinization, peri-implant probing, bleeding, and healing). Data were analyzed using a paired t test. RESULTS: Pain intensity significantly decreased from immediate postoperative to 7 days in both scalpel (49.87 &#xb1; 6.78, t = 28.48, df = 14, P .001) and diode laser (7.67 &#xb1; 7.58, t = 3.91, df = 14, P = .002) groups. Immediately after surgery, pain scores were significantly higher in the scalpel group compared with the diode laser group (94.53 &#xb1; 4.45 vs 46.93 &#xb1; 5.85, t = 25.076, df = 26.151, P .001). Although pain decreased in both groups by day 7, the scalpel group continued to exhibit significantly greater pain (44.67 &#xb1; 5.96 vs 39.27 &#xb1; 3.73, t = 2.974, df = 23.513, P = .007). Impression time (P = .231) and gingival keratinized tissue (P = .736) did not differ significantly between the scalpel and diode laser approaches. At week 6, the scalpel group exhibited a significantly higher mean peri-implant bleeding index (2.60 &#xb1; 0.507) compared with the laser group (0.07 &#xb1; 0.258, P .001). However, after 12 weeks, no significant difference was observed (1.58 &#xb1; 0.19 vs 1.55 &#xb1; 0.21, P = .748). Laser surgery produced significantly better early wound healing at all intervals (P .001), while intraoperative bleeding was more common with the scalpel technique than with the diode laser (100.0% vs 66.7%, P = .042). CONCLUSION: Compared with the scalpel method, the diode laser method resulted in a significant reduction in pain intensity, improved wound healing, and less peri-implant bleeding during the stage-two dental implant surgery.

Humans

Total ankle replacement versus nonoperative management for end-stage ankle osteoarthritis: A comparative analysis.

BACKGROUND: The optimal management of end-stage ankle osteoarthritis remains debated. This study compared short-term outcomes between non-operative treatment, total ankle replacement (TAR), and cases in which indicated surgery was delayed. METHODS: In this secondary analysis of prospectively collected data, treatment survival, Foot and Ankle Outcome Score (FAOS), and patient satisfaction were assessed at baseline and at 1- and 2-year follow-up. RESULTS: In a total of 316 patients one-year treatment survival was highest for TAR (99.3%), followed by NOM (94.4%) and delayed surgery (80.9%). TAR demonstrated significantly superior FAOS pain and quality-of-life scores compared with NOM and delayed surgery. Delayed surgery was associated with significantly worse pain and quality-of-life outcomes. Patient satisfaction was highest in the TAR group and lowest in the delayed surgery group. CONCLUSIONS: TAR provides superior pain relief, quality of life, and satisfaction compared with non-operative management in end-stage ankle OA. While NOM remains a valid option for selected patients, delaying indicated surgery results in inferior outcomes, underscoring the importance of timely, shared decision-making.

Humans

Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.

OBJECTIVE: To evaluate whether an opioid-sparing anesthesia strategy (OSA), based on opioid-free anesthesia (OFA), improves early postoperative recovery quality and optimizes functional outcomes after total knee arthroplasty (TKA), compared with conventional opioid-based anesthesia (OBA). DESIGN: A randomized controlled trial with blinding of patients, surgeons, and outcome assessors. SETTING: Single center, July 2025 to February 2026. PATIENTS: 98 adult patients scheduled for elective unilateral TKA. INTERVENTION: Patients were randomized to the OSA or OBA group. The OSA regimen used esketamine and dexmedetomidine as the primary analgesic backbone, whereas the OBA regimen was opioid-based. Both groups received preoperative femoral nerve block and were administered oxycodone at skin incision and closure. Postoperatively, both groups received the same multimodal analgesia and patient-controlled analgesia. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. Secondary outcomes included 48-h QoR-15; Oxford Knee Score (OKS) and EQ-5D-3L at 1 and 3&#xa0;months; high pain at 1&#xa0;month and chronic postsurgical pain at 3&#xa0;months. Exploratory outcomes included postoperative C-reactive protein (CRP), and postoperative nausea and vomiting (PONV), among others. RESULTS: At 24&#xa0;h postoperatively, QoR-15 was higher in the OSA group than in the OBA group (118.4&#xa0;&#xb1;&#xa0;11.5 vs 113.3&#xa0;&#xb1;&#xa0;12.2; adjusted difference 5.12, 95% CI 0.51-9.74; P&#xa0;=&#xa0;0.029), and this advantage persisted at 48&#xa0;h (adjusted difference 5.54, 95% CI 1.57-9.52; P&#xa0;=&#xa0;0.007). The OSA group had a lower incidence of PONV (P&#xa0;=&#xa0;0.025) and lower postoperative CRP levels (P&#xa0;=&#xa0;0.001). At 1&#xa0;month, OKS was higher in the OSA group (adjusted difference 2.31, 95% CI 0.34-4.27; P&#xa0;=&#xa0;0.022), with no significant differences in other secondary outcomes. CONCLUSION: In TKA, this OFA-based OSA strategy improved early postoperative QoR-15 scores. However, the QoR-15 difference did not reach the minimal clinically important difference, so its clinical relevance remains uncertain.

Humans

Perioperative analgesic efficacy of ultrasound-guided erector spinae plane block and posterior transversus abdominis plane block in paediatric patients undergoing open pyeloplasty: A prospective randomised trial.

PURPOSE: Open pyeloplasty in the paediatric population involves extensive tissue dissection and manipulation, resulting in significant postoperative pain. Ultrasound-guided fascial plane blocks have emerged as an important component of multimodal analgesia in abdominal surgeries. This study compared the analgesic efficacy of ultrasound-guided Erector spinae plane block (ESP) and posterior transversus abdominis plane (pTAP) block in children undergoing open pyeloplasty. METHODS: It is a prospective, randomised, double-blind study conducted at a single paediatric centre in a tertiary care hospital in Asia from January 2022 to June 2023. 40 ASA I-II children were randomised to receive either the ESP block (Group E) or the pTAP block (Group T). Both groups received 0.4 ml/kg, 0.2% ropivacaine with 1 mcg/kg dexmedetomidine. Children with an allergy to local anaesthetics, cardiac, renal or hepatic dysfunction and local site infection were excluded. The primary outcome was cumulative 24 h postoperative acetaminophen consumption. Secondary outcomes included the effects on intraoperative hemodynamics, perioperative opioid consumption, FLACC and Watcha scores, time to first rescue analgesia, and any block-related complications. RESULTS: Weight-normalised 24 h postoperative acetaminophen consumption was significantly lower in the ESP group (13.5 &#xb1; 4.7 mg/kg) compared to the pTAP group (25.4 &#xb1; 8.3 mg/kg), with a mean difference of -12 mg/kg (p < 0.001, 95%CI -16 to -7.6). The median time to first rescue analgesia was significantly longer in the ESP group (18 h [95% CI, 18-24]) than in the TAP group (9 h [95% CI, 6-12]), p < 0.001. Although FLACC scores were significantly lower in the ESP group at 30 min and 12 h postoperatively, the overall longitudinal analysis using a linear mixed-effects model showed no significant difference in the trend of FLACC scores over time between the two groups. There were no block-related complications. CONCLUSION: Ultrasound-guided ESPB provides better, longer-lasting analgesia than posterior TAP block in children undergoing open pyeloplasty. Hence, it may serve as an effective component of multimodal pain management in paediatric open pyeloplasty. CTRI REGISTRATION (CTRI/2022/04/041876) DATED 13/04/2022): https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=67747&EncHid=42257.14515&modid=1&compid=19.

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

Machine learning-ready genomic biomarkers: ATF3 polymorphisms predict postoperative analgesic demand through AI-compatible phenotyping.

PURPOSE: To determine whether ATF3 polymorphisms can serve as genetic biomarkers for machine learning-based precision analgesia by establishing a genotype-phenotype association suitable for predictive modeling of postoperative opioid requirements. METHODS: In a prospective cohort of 167 adults undergoing abdominal surgery, ATF3 SNPs rs3122721 and rs3125293 were genotyped. A structured dataset architecture was developed to represent genetic profiles as input features for supervised learning models, enabling translational analysis of genotype&#x2011;dependent opioid consumption over 72&#xa0;h. RESULTS: Patients with homozygous genotypes of the ATF3 SNPs had significantly higher opioid requirements than non&#x2011;carriers, despite reporting similar subjective pain scores. This consistent genotype&#x2011;dependent pattern provided a clinically relevant phenotype suitable for integration into predictive algorithms. CONCLUSION: ATF3 genotyping offers a promising biomarker for computationally informed precision analgesia. By linking genomic variability to clinically meaningful outcomes within a structured clinical and genomic framework, this approach supports the future development of risk-stratified clinical decision-support systems to optimize postoperative pain management.Trial registration ChiCTR1900021991, registered 30 April 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13755-026-00480-9.

ATF3

Mindfulness and Sex Education for Sexual Dysfunction in Breast Cancer Survivors: Mediators and Moderators of Treatment Outcome.

Mindfulness-based cognitive therapy (MBCT) and supportive-expressive sex education therapy (STEP) are effective group treatments for sexual dysfunction after breast cancer (BrCa). We explored mediators and moderators of outcomes following the 8-week groups. BrCa survivors (n&#x2009;=&#x2009;116, mean age&#x2009;=&#x2009;49.9&#x2009;&#xb1;&#x2009;9.5) were randomized to group and completed measures before, immediately after, and 6&#x2009;months after treatment. Mediators assessed were changes in depression, chronic pain acceptance, pain catastrophizing, and trait mindfulness. Potential moderators included age, treatment expectations, baseline mental health, cancer treatment duration, use of chemotherapy, and adjuvant endocrine therapy. Longitudinal mediation and moderation were assessed using linear mixed models. Increases in pain acceptance mediated improvements in sexual desire and reductions in both sexual distress and vaginal pain. Decreases in pain catastrophizing mediated improvements in sexual distress. Higher expectations for treatment led to greater reductions in sexual distress. Those with low baseline anxiety showed greater improvements in desire and distress. Low baseline depression predicted greater improvements in desire, but only in the STEP arm. Older STEP participants improved significantly more than younger STEP participants. Cancer-related treatment variables, and the impact of adjuvant endocrine therapy, had differential effects on outcomes based on the treatment arm of the study. In conclusion, treatments aimed at improving pain acceptance and pain catastrophizing are likely to promote improvements in sexual health among BrCa survivors, and factoring in patients' expectations about treatment improvements, depression and anxiety, age, duration of cancer treatment, chemotherapy, and adjuvant hormonal therapy may help to guide treatment recommendations for sexual dysfunction.

Humans

Initial 4-Year Experience With Microaxial Flow Pumps Within a Tertiary Centre in Regional Australia.

BACKGROUND & AIM: The Microaxial Flow Pump (MFP) is a miniaturised rotary pump that aspirates blood from the left ventricle and expels it into the ascending aorta. It unloads the left ventricle and increases mean arterial pressure and cardiac output. MFP is most commonly utilised in cardiogenic shock, for protected percutaneous coronary intervention (PCI), and for ventricular offloading in veno-arterial extracorporeal membrane oxygenation (VA-ECMO). METHOD: We conducted a retrospective review of all patients who underwent MFP insertion at John Hunter Hospital, Australia. Categorical data are represented as counts and percentages, with continuous variables described as means with standard deviations. RESULTS: Twenty-three MFP devices were inserted between September 2020 and May 2024. Five (22%) were for protected PCI, three (13%) for venting with VA-ECMO (ECPELLA), and 15 (65%) for acute coronary syndrome (ACS) and cardiogenic shock. The median age for the overall cohort was 62 years, with a 74% male predominance. Eighty percent of the protected PCI cohort were elective outpatient procedures, and there were no deaths in this cohort. The mortality in the ECPELLA group was 67%. Thirteen (87%) of the patients with cardiogenic shock presented with an anterior infarct, and 53% had cardiac arrest on admission. The overall morality in the cardiogenic shock cohort was 40%. Complications in this cohort included limb ischaemia in four patients (17%) and site bleeding in seven patients (30%). Four patients (17%) required vascular surgery intervention. CONCLUSION: Our initial experience showed the use of MFP in a tertiary centre was safe and feasible, allowing progression from protected percutaneous intervention to acute cardiogenic shock.

Humans

Multilevel Revision Percutaneous Vertebroplasty in Elderly Patients With Osteoporotic Thoracolumbar Fractures: A Retrospective Cohort Study.

PURPOSE: Vertebral compression fractures (VCFs) are common complications of osteoporosis in elderly patients. Percutaneous vertebroplasty (PVP) provides pain relief and functional improvement, but some patients require revision due to refracture, cement failure, or new symptomatic levels. While outcomes of primary and multilevel augmentation have been described, systematic data on multilevel revision PVP remain rare. The aim of this study was to evaluate pain relief, functional improvement, and perioperative safety after three- and four-level revision PVP in elderly patients with osteoporotic thoracolumbar fractures. METHODS: This retrospective, single-center cohort included patients aged 75-85&#x2009;years who underwent revision PVP between August 2019 and November 2023. Eligible cases had a history of prior PVP and required repeat augmentation of three or four vertebral levels in a single session. Visual Analogue Scale (VAS) scores for pain and Oswestry Disability Index (ODI) for functional disability were recorded preoperatively and at 1-, 3-, 6-, and 12-month follow-up. RESULTS: Nine patients were analyzed. Revision involved three levels in five patients and four levels in four patients, with a mean interval of 14.1&#x2009;months after the index procedure. Mean VAS improved from 8.3&#x2009;&#xb1;&#x2009;0.7 preoperatively to 3.2&#x2009;&#xb1;&#x2009;0.6 at 12&#x2009;months (61% reduction, p&#x2009;<&#x2009;0.01). ODI improved from 75.2%&#x2009;&#xb1;&#x2009;3.4% to 26.9%&#x2009;&#xb1;&#x2009;2.7% (64% reduction, p&#x2009;<&#x2009;0.01). All patients exceeded the minimal clinically important difference thresholds. No perioperative complications such as cement leakage, neurological deficits, or pulmonary events were observed. CONCLUSION: Three- and four-level revision PVP provided significant pain relief and functional improvement in elderly patients with osteoporotic fractures, without increased complication rates. To our knowledge, this represents one of the first reports addressing this topic, suggesting it is an effective option in carefully selected patients.

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

Digital Mindfulness Intervention for Pregnant Women With Affective Disorders and Acute Stress Reactions: Prespecified Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Pregnant women with ICD-10 (International Statistical Classification of Diseases, Tenth Revision) affective or stress-related disorders face an elevated risk of perinatal depression and anxiety, yet evidence on digital nonpharmacologic interventions for this population remains limited. OBJECTIVE: This study evaluated the effectiveness of an 8-week digital mindfulness-based intervention (eMBI) compared with treatment as usual (TAU) among pregnant women with ICD-10 affective or stress-related disorders participating in a randomized controlled trial (RCT). METHODS: This prespecified secondary analysis was conducted within a multicenter RCT in Baden-W&#xfc;rttemberg, Germany. Pregnant women aged 18 years and older with elevated depressive symptoms (Edinburgh Postnatal Depression Scale [EPDS]>9) and ICD-10-diagnosed affective or stress-related disorders were randomized 1:1 to eMBI or TAU. The intervention consisted of 8 weekly app-based mindfulness sessions (45 min each) delivered during gestational weeks 29-36, with no direct therapist contact. The primary outcome was continuous depressive symptom severity measured with the EPDS at 4-6 weeks post partum. Secondary outcomes included the EPDS at 6 months post partum, generalized anxiety (State-Trait Anxiety Inventory-State [STAI-S], State-Trait Anxiety Inventory-Trait [STAI-T]), and Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R). Analyses followed the intention-to-treat (ITT) principle, using mixed models for repeated measures and multiple imputation. RESULTS: Of the 5299 screened women, 147 met the inclusion criteria for this subgroup analysis (intervention group [IG] had n=73 women and control group had n=74 women). Groups were comparable at baseline. The IG showed significantly greater reductions in EPDS scores at gestational week 34 (&#x394;=-2.21, P=.01), week 36 (&#x394;=-3.25, P=.01), and 4-6 weeks post partum (&#x394;=-4.81, P=.007). Treatment effects remained robust under conservative missing-data assumptions. At 4-6 weeks post partum, a higher proportion of participants in the IG achieved clinically meaningful improvement (31/73, 42.5% vs 21/74, 28.4%; adjusted odds ratio 1.56, 95% CI 1.19-2.05; P=.001). Anxiety outcomes followed a similar pattern, whereas pregnancy-related anxiety did not differ between groups. CONCLUSIONS: In this prespecified subgroup of pregnant women with ICD-10 affective or stress-related disorders, the eMBI was associated with clinically meaningful reductions in depressive symptoms from late pregnancy to 4-6 weeks post partum. Effects at 6 months post partum were attenuated and less stable across missing-data assumptions. These findings support eMBIs as a scalable, nonpharmacological adjunct to perinatal mental health care for women with affective or stress-related disorders, while confirmation in adequately powered trials with strategies to reduce postpartum attrition is warranted.

Humans

Ketamine Plus Midazolam versus Fentanyl Plus Midazolam for Sedation and Analgesia during Image-guided Procedures in Interventional Radiology: Randomized Clinical Trial.

Background Opioid-benzodiazepine regimens remain common for radiologist-administered procedural sedation despite respiratory and analgesic effectiveness concerns. Purpose To compare intraprocedural pain and patient-reported experience between ketamine/midazolam and fentanyl/midazolam during image-guided procedural sedation. Materials and Methods This randomized clinical trial was conducted at a single academic center between June 2025 and February 2026. Adults undergoing image-guided lung or bone biopsy or abscess drainage were randomized to fentanyl/midazolam or ketamine/midazolam administered by interventional radiologists. Procedures were performed using US, CT, CT fluoroscopy, or combined CT and US guidance. The primary outcome was maximum intraprocedural pain (0-10 on the Numeric Rating Scale). Secondary outcomes included sedation depth, physiologic parameters, oxygen desaturation, patient-reported experience assessed using a modified Heidelberg questionnaire, and complications. Results Among 264 randomized procedures (132 procedures per group) in 260 participants (median age, 68 years [IQR, 61-75 years]; 135 [52%] female), ketamine/midazolam resulted in lower maximum intraprocedural pain than fentanyl/midazolam (mean difference, -1.4 points [95% CI: -2.0, -0.8]; P < .001). Pain scores greater than 4 occurred less frequently with ketamine/midazolam (2.3% vs 17%; absolute difference, 14 percentage points [95% CI: 8, 21]; P < .001). Ketamine/midazolam was associated with higher nadir oxygen saturation (mean difference, +1.4% [95% CI: 0.6, 2.2]; P = .001) and fewer oxygen desaturation events below 90% (three [2.3%] vs 13 [9.8%]; absolute difference, 7.6 percentage points [95% CI: 1.9, 13.3]; P = .02). Ketamine/midazolam produced deeper sedation and higher intraprocedural systolic blood pressure. Hallucinations occurred more frequently with ketamine/midazolam (15 [11.4%] vs five [3.8%]; absolute difference, 7.6 percentage points [95% CI: 1.3, 13.9]; P = .03), though overall procedural comfort, reduced recall, and perceived adequacy of sedation were improved. Procedure-related and sedation-related complications did not differ between groups. Conclusion Radiologist-administered ketamine/midazolam during image-guided procedural sedation improved analgesia and patient-reported experience with fewer hypoxemic events and no increase in complications compared with fentanyl/midazolam. Clinical trial registration no. NCT07040163

Aged

Repeated scoring with the adult appendicitis score improves the sensitivity and the specificity of appendicitis diagnosis in patients with early equivocal signs of appendicitis: a secondary analysis.

PURPOSE: The utilization of computed tomography in the early stage of acute appendicitis may result in overdiagnosis and unnecessarily expose patients to ionising radiation. The Adult Appendicitis Score (AAS) can be used to select patients for imaging. Observation and re-scoring in the DIAMOND trial reduced the need for imaging. Now, we wanted to determine if the change in AAS (&#x2206;AAS) can serve as a diagnostic tool to select patients for imaging even more precisely. METHODS: Eighty-eight patients with early equivocal appendicitis participated in the observation arm of the DIAMOND trial. The data for these patients were reanalysed, and &#x2206;AAS during the observation was calculated. The baseline AAS, final AAS, and the change in C-reactive protein (&#x2206;CRP) were selected as reference standards. RESULTS: Eighty-three patients with complete data were included in the analysis. The AUROC (Area Under the Receiver Operating Characteristic) values are as follows: &#x2206;AAS, 0.932 (95% CI 0.868-0.996); baseline AAS, 0.629 (95% CI 0.498-0.760); final AAS, 0.936 (95% CI 0.886-0.987); and &#x2206;CRP, 0.796 (95% CI 0.696-0.897). Using receiver operating characteristic curves, we established the thresholds for low (AAS&#x2009;&#x2264;&#x2009;-2), intermediate (AAS -1 to 0), and high (AAS&#x2009;&#x2265;&#x2009;1) probability of appendicitis. The negative predictive value for the low-probability group and the positive predictive value for the high-probability group concerning acute appendicitis were 97% and 94%, respectively. CONCLUSION: Patients with equivocal signs of appendicitis may benefit from short observation and the calculation of &#x2206;AAS to reduce overdiagnosis and exposure to excessive imaging. REGISTRATION: The DIAMOND trial was officially registered on ClinicalTrials.gov (NCT02742402) on April 13, 2016.

Adult