Prehospital Pulse-Dose Glucocorticoid in ST-Segment Elevation Myocardial Infarction: The PULSE-MI Randomized Clinical Trial.

Importance: In patients with ST-segment elevation myocardial infarction (STEMI), acute inflammation is related to the extent of myocardial damage and may increase infarct size. Thus, administration of pulse-dose glucocorticoid in the very early phase of infarction may reduce infarct size. Objective: To determine the cardioprotective effect of prehospital pulse-dose glucocorticoid in patients with STEMI. Design, Setting, and Participants: This was a 1:1 investigator-initiated, blinded, placebo-controlled, randomized clinical trial conducted between November 14, 2022, and October 17, 2023, with last follow-up on January 17, 2024. Patients 18 years and older with less than 12 hours of acute chest pain and STEMI were included in the prehospital setting throughout the Region Zealand and Capital Region of Denmark and transferred to Rigshospitalet, Denmark. Intervention: Patients were randomly allocated to intravenous glucocorticoid (methylprednisolone, 250 mg) or placebo in the prehospital setting. Main Outcomes and Measures: The primary outcome was final infarct size on cardiac magnetic resonance (CMR) at 3 months. The power calculation was based on an anticipated final infarct size of 13%. Secondary outcomes included CMR outcomes on acute scan and at 3 months, peak of cardiac biomarkers, clinical end points at 3 months, and adverse events. Results: Of 530 included patients (median [IQR] age, 65 [56-75] years; 418 male [78.9%]) with STEMI, 401 (76%) were assessed for the primary outcome, with 198 patients treated with glucocorticoid and 203 with placebo. Median final infarct size was similar in the treatment groups (glucocorticoid, 5%; IQR, 2%-11% vs placebo, 6%; IQR, 2%-13%; P = .24). Compared with placebo, the glucocorticoid group had smaller acute infarct size (odds ratio, 0.78; 95% CI, 0.61-1.00), less microvascular obstruction (relative risk ratio, 0.83; 95% CI, 0.71-0.99), and greater acute left ventricular ejection fraction (mean difference, 4.44%; 95% CI, 2.01%-6.87%). Other secondary outcomes were similar in both groups. Conclusions and Relevance: In patients with STEMI, treatment with prehospital pulse-dose glucocorticoid did not reduce final infarct size after 3 months. However, the trial was likely underpowered as the final infarct size was smaller than anticipated. The glucocorticoid group had improved acute parameters compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT05462730.

Electrical impedance detects early stages of bone healing: An in vivo explanatory study of tibial fractures in rabbits.

Purpose: Healing after bone fracture is assessed by clinical examination and frequent radiographs, which expose patients to radiation and lack standardisation. This study aimed to explore electrical impedance patterns during bone healing using electrical impedance spectroscopy in 18 rabbits subjected to tibial fracture stabilised with an external fixator. Methods: Impedance was measured daily across the fracture site at a frequency range of 5 Hz to 1 MHz. Biweekly radiographs were analysed using modified anterior-posterior (AP) radiographic union score of the tibia (RUST). The animals were divided into three groups with different follow-up times: 1, 3 and 6 weeks for micro-computer tomography and mechanical testing. Results: A decreasing trend in impedance was observed over time for all rabbits at lower frequencies. Impedance closest to 5 Hz showed a statistically significant decrease over time, with greatest decrease occurring during the first 7 postoperative days. At 5 Hz, a statistically significant correlation was found between impedance and the modified AP RUST score and between impedance and bone volume fraction. Conclusions: This study showed that the electrical impedance can be measured in vivo at a distance from the fracture site with a consistent change in impedance over time and revealed significant correlation between increasing radiographic union score and decreasing impedance. Level of Evidence: Not applicable.

Pre-hospital pulse glucocorticoid therapy in patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention: a randomized controlled trial (PULSE-MI).

BACKGROUND: Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI. METHODS: This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark, will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 h duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) 3 months after STEMI. Secondary outcomes comprise key CMR efficacy parameters, clinical endpoints at 3 months, the peak of cardiac biomarkers, and safety. DISCUSSION: We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation and thus reduces final infarct size in patients with STEMI treated with primary PCI. TRIAL REGISTRATION: EU-CT number: 2022-500762-10-00; Submitted May 5, 2022. CLINICALTRIALS: gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022.

Positive predictive values in clinical screening for developmental dysplasia of the hip.

AIM: To establish the positive predictive value (PPV) of clinical hip examinations performed by referrers in the Danish screening programme for Developmental Dysplasia of the Hip (DDH) utilising three definitions of true positive DDH diagnosis. METHODS: We retrospectively identified 290 children (169 female) referred during a 4-year period to the orthopaedic outpatient clinic at our institution with a positive clinical hip examination. Positive predictive value was calculated for clinical hip examinations across three definitions of a true positive clinical hip examination for all referrers and subgroups consisting of general practitioners, midwives and paediatricians. The PPV for clinical hip examinations was calculated for paediatric orthopaedic surgeons using one of the three definitions. RESULTS: Positive predictive value of clinical hip examinations for all referrers were 5.4%, 3.6% and 1.8% with the definition of a true positive DDH diagnosis defined as clinical instability found by orthopaedic surgeon, ultrasound classification ≥Graf IIc or both definitions combined, respectively. Positive predictive value of clinical hip examinations performed by orthopaedic surgeons was 33.3% with a true positive clinical examination defined as an ultrasound classification ≥Graf IIc. CONCLUSION: We conclude that the positive predictive value of clinical hip examinations made by referrers in the Danish screening programme for DDH is low.