NEJM (The New England Journal of Medicine)

📚 Summary: CHASERR encodes a long noncoding RNA adjacent to the CHD2 gene, which is linked to developmental and epileptic encephalopathy.

👶 Findings: In three unrelated children with a severe early-onset neurodevelopmental disorder, de novo deletions in the CHASERR locus were identified. The children exhibited encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination, distinct from CHD2 haploinsufficiency phenotypes.

🔍 Mechanism: The deletion led to increased CHD2 protein levels in patient-derived cell lines and heightened expression of the CHD2 transcript.

▪️ Conclusion: CHD2 shows bidirectional dosage sensitivity; further evaluation of lncRNA genes near Mendelian disorder-associated genes is recommended.

📚 Background: Treatments for Dupuytren’s contracture include limited fasciectomy and collagenase injection, but comparative effectiveness data are limited.

🩺 Methods: This pragmatic, two-group, randomized, controlled trial assessed the noninferiority of collagenase injection compared to limited fasciectomy in patients with moderate Dupuytren’s contracture. The primary outcome was the Patient Evaluation Measure–Hand Health Profile score at 1 year post-treatment.

📊 Results: Among 599 participants, the mean score on the Patient Evaluation Measure at 1 year was 17.8 for collagenase and 11.9 for fasciectomy, with a noninferiority margin not met. Complications were lower in the collagenase group (1.8% vs. 5.1%).

▪️ Conclusions: Collagenase injection was not noninferior to limited fasciectomy regarding hand health outcomes at 1 year.

📚 Background: Amivantamab combined with lazertinib demonstrates significant antitumor activity in previously untreated patients with EGFR-mutated advanced non-small-cell lung cancer (NSCLC).

🩺 Methods: This phase 3 trial randomized patients with EGFR mutations to receive either amivantamab-lazertinib, osimertinib, or lazertinib, assessing progression-free survival as the primary endpoint.

📊 Results: The amivantamab-lazertinib group had a median progression-free survival of 23.7 months, compared to 16.6 months for osimertinib. High objective response rates were observed in both groups.

▪️ Conclusions: Amivantamab-lazertinib offers superior first-line efficacy over osimertinib in treating EGFR-mutated advanced NSCLC.

📚 Background: Steroidal mineralocorticoid receptor antagonists are effective for heart failure with reduced ejection fraction, but their role in mildly reduced or preserved ejection fraction is unclear. This study evaluates finerenone, a nonsteroidal mineralocorticoid receptor antagonist, in this population.

🩺 Methods: In a double-blind trial, patients with heart failure and ejection fraction ≥40% were randomly assigned to finerenone or placebo.

📊 Results: Finerenone significantly reduced total worsening heart failure events and cardiovascular deaths compared to placebo.

▪️Conclusions: Finerenone offers a valuable option for heart failure patients with mildly reduced or preserved ejection fraction.

2024 Albert Lasker Award for Basic Medical Research.

Conclusion: Five-fraction SBRT was effective and noninferior to control radiotherapy for biochemical or clinical failure, offering a viable treatment option for patients with localized prostate cancer.