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#原始研究

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Oct 2Fri
  1. Nat Med61

    Effects of semaglutide on kidney disease in type 2 diabetes: a randomized placebo-controlled trial.

    Semaglutide's kidney protection in type 2 diabetes and chronic kidney disease may work through reduced vascular resistance and prevention of fibrosis. In a 52-week randomized trial of 106 participants, semaglutide 1 mg weekly lowered renal artery resistive index and stabilized the apparent diffusion coefficient versus placebo, while MRI coprimary outcomes (R2* oxygenation, perfusion, T1 inflammation) were unchanged. Paired biopsies showed pronounced effects on glomerular endothelial cells with fewer nearby immune cells.

  2. nature.com61

    Effects of semaglutide on kidney disease in type 2 diabetes: a randomized placebo-controlled trial

    A randomized placebo-controlled trial in individuals with type 2 diabetes probed the kidney-protective mechanisms of semaglutide using kidney histology, multiparametric MRI and transcriptomics. The findings indicate how semaglutide acts on the kidney in this population, moving the evidence beyond its established glucose-lowering effect toward direct renal mechanisms.

    Why it matters: Mechanistic trial data on semaglutide's kidney protection in type 2 diabetes using histology, MRI and transcriptomics.

Sep 29Tue
  1. nature.com54

    A synthetic lethal drug for microsatellite instability cancers

    Inhibition of the Werner syndrome helicase (WRN) enzyme exploits a new synthetic lethal vulnerability in cancers with microsatellite instability, a phase 1 trial shows. The approach offers a new way to target these tumors beyond immune checkpoint inhibition. No efficacy numbers are reported in the material.

    Why it matters: First clinical evidence that WRN inhibition can target microsatellite instability cancers beyond checkpoint inhibitors.

Sep 15Tue
  1. Sci Adv55

    Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer.

    Personalized cancer vaccines, delivered as synthetic long peptide or DNA formulations after resection and adjuvant chemotherapy, were safe and immunogenic in pancreatic ductal adenocarcinoma: two phase 1 trials showed no grade ≥3 adverse events and induced polyclonal neoantigen-specific T cell responses confirmed by IFN-γ ELISpot, intracellular cytokine staining, and T cell receptor clonotype reconstruction. Compared with a propensity-matched cohort, vaccine recipients showed a trend toward longer median overall survival (4.4 versus 3.5 years, log-rank P = 0.23). The results establish feasibility of neoantigen vaccination in a tumor considered unresponsive to standard immunotherapy.

    Why it matters: It shows personalized neoantigen vaccines are safe and immunogenic in PDAC, a cancer unresponsive to standard immunotherapy.

Sep 14Mon
  1. JAMA57

    Gastric Residual Volume Assessment in Critically Ill Children: The GASTRIC-PICU Randomized Clinical Trial.

    Not routinely assessing gastric residual volume in ventilated critically ill children was noninferior to 6-hourly assessments for survival and ventilator-free days at 30 days (median 25 days in both groups; adjusted OR 0.95 [95% CI 0.86-1.05]). In the trial of 4700 children in pediatric intensive care units in the UK and Switzerland, dropping routine GRV checks also improved feeding: mean energy requirements achieved by 72 hours were 80.3% versus 76.8% (adjusted mean difference 3.2 percentage points, P < .001).

    Why it matters: A large randomized noninferiority trial shows routine GRV checks can be dropped in PICU enteral feeding without harming outcomes.

Sep 11Fri
  1. JAMA69

    Loberamisal for Acute Ischemic Stroke: The LAIS Randomized Clinical Trial.

    Intravenous loberamisal, given once daily for 10 days on top of standard care, improved functional recovery after acute ischemic stroke in the phase 3 LAIS trial. Among 997 treated adults in China with NIHSS scores of 7 to 20 within 48 hours of onset, 69.7% reached a 90-day mRS score of 0 to 1 versus 56.3% with placebo (RR, 1.24), with no increase in adverse events, serious adverse events, or mortality.

    Why it matters: Phase 3 evidence that a PSD-95 and α2-GABAA dual-target agent improves stroke outcomes, a field with few effective therapies.

Sep 8Tue
  1. Lancet73

    Porcine kidney xenotransplantation as a bridge to allotransplantation: a first-in-human study.

    A gene-edited porcine kidney (EGEN-2784) transplanted into a patient with end-stage kidney disease functioned immediately and maintained dialysis independence for 271 days before failing after immunosuppression reduction, with thrombotic microangiopathy despite negative donor-specific crossmatch. No porcine pathogen transmission or anti-HLA antibody change occurred. 82 days after nephrectomy, the patient received a human kidney allotransplant with immediate function and no sensitisation during 231 days of follow-up.

    Why it matters: First living-recipient porcine kidney xenograft shows 271 days of dialysis independence and successful bridge to allotransplantation without sensitisation.

Sep 5Sat
  1. Nat Med61

    Inhaled siRNA therapy targeting RAGE for pulmonary inflammation: a first-in-human randomized trial.

    Inhaled ARO-RAGE, a lung-epithelium-targeted siRNA against pulmonary RAGE mRNA, was safe and well tolerated in a first-in-human randomized trial in 58 healthy volunteers and 19 patients with asthma. Plasma levels were low, consistent with drug retention in the lung, and prolonged dose-responsive decreases in serum and bronchoalveolar lavage sRAGE indicated effective pulmonary target engagement. The results support continued clinical development of inhaled therapeutic siRNA for pulmonary inflammation.

    Why it matters: First-in-human data show an inhaled siRNA can safely engage a lung target with minimal systemic exposure.

Sep 3Thu
  1. N Engl J Med64

    Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer.

    Daraxonrasib (RMC-6236), an oral RAS(ON) multiselective inhibitor, showed antitumor activity in 136 previously treated patients with advanced RAS-mutant NSCLC: objective response occurred in 31% at doses of 120 mg or less, 34% at 160 to 220 mg, and 37% at 300 mg once daily. Adverse events of grade 3 or higher occurred in 54%, including four grade 5 events, with rash, diarrhea, nausea, vomiting, and mucositis or stomatitis each affecting at least 30% of patients.

    Why it matters: First safety and efficacy data for a pan-RAS inhibitor across multiple doses in previously treated RAS-mutant NSCLC.

Sep 1Tue
  1. JAMA66

    Dapagliflozin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial.

    Dapagliflozin started one day before elective cardiac surgery cut postoperative acute kidney injury nearly in half. Among 784 adults randomized at Dutch hospitals, AKI within 7 days occurred in 28% of the dapagliflozin group versus 52% on placebo (relative risk, 0.54; P < .001). Four perioperative doses of 10 mg offer a preventive strategy where none had been identified.

    Why it matters: It identifies the first medication shown in a randomized trial to prevent AKI after elective cardiac surgery.

Aug 31Mon
  1. N Engl J Med64

    Catheter-Directed Thrombolysis in Intermediate-High-Risk Pulmonary Embolism.

    Catheter-directed thrombolysis with alteplase plus anticoagulation reduced the composite of death, recurrent pulmonary embolism, or cardiorespiratory decompensation or collapse within 7 days in intermediate-high-risk acute pulmonary embolism: 0.7% vs 6.8% with anticoagulation alone (relative risk 0.10, P<0.001). In 558 randomized patients, clinically relevant bleeding occurred in 4.6% vs 5.0% and major bleeding in 1.4% vs 2.2%; intracranial hemorrhage occurred in 2 thrombolysis patients and none on standard care.

    Why it matters: Randomized trial showing a large 7-day benefit of catheter-directed thrombolysis in intermediate-high-risk PE without excess clinically relevant bleeding.

  2. N Engl J Med60

    Timing of PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation.

    In patients with severe aortic stenosis and coronary artery disease undergoing transcatheter aortic-valve implantation (TAVI), doing TAVI before PCI was noninferior to the conventional PCI-first approach. At 1 year, the composite endpoint of death, myocardial infarction, ischemia-driven revascularization, rehospitalization, or major bleeding occurred in 22.2% of the TAVI-first group versus 24.2% of the PCI-first group (risk difference -2.0 percentage points; 95% CI -7.4 to 3.4). This randomized trial of 986 patients at 48 European centers supports resequencing the two procedures.

    Why it matters: It provides randomized evidence on procedural sequencing in a common TAVI population where practice has been unestablished.

Aug 30Sun
  1. N Engl J Med63

    Clopidogrel or Dual Antiplatelet Therapy in High-Ischemic-Risk Patients.

    Clopidogrel monotherapy was noninferior to extended dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin for net adverse clinical events in high-ischemic-risk patients 12 months after drug-eluting stent implantation: 5.0% versus 5.1% at 24 months (risk difference, -0.1 percentage points; 90% CI, -1.3 to 1.2). The trade-off was clear, as the key secondary ischemic end point occurred in 3.7% with monotherapy versus 1.6% with DAPT (hazard ratio, 2.33), while BARC type 2, 3, or 5 bleeding occurred in 1.8% versus 4.1% (hazard ratio, 0.43).

    Why it matters: It shows clopidogrel monotherapy spares bleeding but raises ischemic events in high-risk patients after stenting.

  2. N Engl J Med62

    Prasugrel versus Ticagrelor in Acute Coronary Syndromes.

    A default prasugrel policy did not reduce ischemic events compared with a default ticagrelor policy after percutaneous coronary intervention for acute coronary syndrome. In 17,095 Swedish patients, the composite of death, myocardial infarction, or stroke at 1 year occurred in 11.1% under prasugrel versus 11.8% under ticagrelor (adjusted OR 0.90; 95% CI 0.77 to 1.06), with less major bleeding under prasugrel (4.2% vs 4.4%; OR 0.80).

    Why it matters: Head-to-head registry-based randomized comparison of the two preferred P2Y12 inhibitors in routine care.

  3. N Engl J Med72

    Tricuspid-Valve Intervention in Heart Failure.

    Transcatheter tricuspid-valve repair plus medical therapy beat medical therapy alone in patients with symptomatic severe tricuspid regurgitation at high risk of heart-failure events. In 360 randomized patients, the win ratio for the hierarchical composite of death, heart-failure hospitalization, and quality-of-life improvement at 1 year was 2.42 (95% CI, 1.76 to 3.33). Freedom from death or heart-failure hospitalization through 3 years was 52.4% with repair versus 21.0% without (hazard ratio 0.40).

    Why it matters: Randomized evidence that tricuspid-valve repair reduces death and heart-failure hospitalization in severe tricuspid regurgitation.

  4. N Engl J Med69

    Pulmonary Denervation for Heart Failure-Related Pulmonary Hypertension.

    Pulmonary-artery denervation plus guideline-directed medical therapy cut clinical worsening in heart failure-related pulmonary hypertension associated with left heart disease. In 264 randomized patients, the 2-year Kaplan-Meier incidence of clinical worsening was 25.7% with denervation versus 51.5% with medical therapy alone (hazard ratio 0.49, P = 0.006). It offers a procedural option beyond drugs for this population.

    Why it matters: First multicenter randomized trial to show pulmonary-artery denervation reduces clinical worsening in left heart disease-associated pulmonary hypertension.

Aug 29Sat
  1. Lancet49

    Safety and efficacy of the 0/1 h pathway for myocardial infarction in the emergency department: an international, pragmatic, stepped-wedge, cluster-randomised, controlled trial.

    Implementing the guideline-recommended 0/1 h troponin pathway was non-inferior to a 0/3 h pathway for the 30-day composite of death from any cause or new type 1 myocardial infarction, meeting the prespecified non-inferiority margin, in 67 624 emergency department presentations with suspected myocardial infarction at 19 hospitals in ten countries. It did not shorten emergency department length of stay, with a median of 309 min in both groups. Faster blood draws alone should not be expected to improve emergency department throughput.

  2. N Engl J Med65

    Atorvastatin, Cardiovascular Events, and Disability-free Survival in Older Adults.

    Atorvastatin 40 mg daily lowered major cardiovascular events versus placebo in community-dwelling adults 70 and older without cardiovascular disease, diabetes, or dementia (hazard ratio 0.70, 95% CI 0.61 to 0.82) over a median 5.9 years in the STAREE trial of 9971 participants. It did not extend disability-free survival: death, dementia, or persistent physical disability occurred at similar rates (hazard ratio 0.94, P=0.25). Serious adverse events occurred in 2.7% of each group.

    Why it matters: First trial to test statins for primary prevention and disability-free survival in adults 70 and older.

Aug 28Fri
  1. N Engl J Med57

    Response-Tailored or Standard-Duration Antibiotic Treatment for Infective Endocarditis.

    Stopping antibiotics early based on clinical response was safe and effective in left-sided infective endocarditis caused by S. aureus, E. faecalis, or streptococcus species. In the POET II trial of 508 stabilized adults, response-tailored therapy gave a median 183 days alive without antibiotics within 6 months versus 169 days with standard 4-to-6-week therapy, and was noninferior for the safety composite (8.2% vs. 10.7%). Relapse of bacteremia or endocarditis was more frequent with tailored therapy (5.1% vs. 1.6%).

    Why it matters: It challenges the consensus of up to 6 weeks of antibiotics for left-sided infective endocarditis with randomized noninferiority data.

Aug 27Thu
  1. N Engl J Med46

    Carbocisteine or Hypertonic Saline for Acute Respiratory Failure.

    Carbocisteine and nebulized hypertonic saline did not shorten mechanical ventilation in critically ill, mechanically ventilated patients with acute respiratory failure and difficult-to-clear secretions. In the 1956-participant factorial trial, median ventilation duration was 186.1 hours with carbocisteine versus 172.7 hours without (adjusted hazard ratio 0.96), and 184.5 versus 174.3 hours with and without hypertonic saline. Both agents caused harm: carbocisteine increased upper gastrointestinal bleeding and hypertonic saline increased bronchoconstriction and hypoxemia during nebulization.

Aug 25Tue
  1. Lancet41

    Multivessel coronary artery bypass grafting via small thoracotomy versus sternotomy (MIST): an investigator-initiated, international, open-label, randomised controlled trial.

    Minimally invasive cardiac surgery CABG via small thoracotomy improved patient-reported physical recovery at 1 month compared with sternotomy CABG in a randomised trial of 170 patients with multivessel coronary artery disease. SF-36 Physical Component Summary scores were significantly higher after MICS CABG (p=0·031). No deaths or strokes occurred in either group up to 12 months.

Aug 24Mon
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