Five papers worth your time — May 18, 2026
This week's PubMed highlights: ibrutinib secures an OS advantage in MCL and makes ASCT redundant (Lancet TRIANGLE); ensitrelvir cuts household COVID transmission by ~67% in the SCORPIO-PEP trial (NEJM); prophylactic tranexamic acid reduces PPH in placenta praevia caesarean births (BMJ); a single psilocybin dose drives 53% remission in MDD at six weeks (JAMA Network Open); and semaglutide cuts heavy drinking days by 41% in AUD with comorbid obesity (Lancet).
This week's indexed batch crosses lymphoma, COVID prophylaxis, obstetric bleeding, psychiatry, and addiction medicine. Two Lancet trials close long-standing questions; one NEJM trial reframes post-exposure COVID management; two more from JAMA Network Open and The Lancet push into treatment territories that lacked any credible Phase 2–3 data until now.
1. TRIANGLE (4.5-year update): ibrutinib lifts OS in MCL, ASCT no longer earns its place
Journal: The Lancet (IF ~168) · Phase 3 RCT · Published 16 May 2026 · PubMed 42134356
Study design: Three-arm, randomized, open-label superiority trial across 165 centres of the European Mantle Cell Lymphoma Network. Arms: (A) R-CHOP/R-DHAP + ASCT; (B) ibrutinib + R-CHOP/R-DHAP + ASCT; (C) ibrutinib + R-CHOP/R-DHAP, no ASCT. Patients aged 18–65.1
Key results: With a median follow-up now exceeding 4 years, ibrutinib-containing arms (B and C) showed improvements in both failure-free survival and overall survival compared with the ibrutinib-free arm (A). Critically, arm C (ibrutinib, no ASCT) was non-inferior to arm B (ibrutinib + ASCT) on FFS, and ASCT added no statistically significant OS benefit in patients already receiving ibrutinib.2
Peer-review status: Published in The Lancet; fully peer-reviewed.
Clinical implication: For transplant-eligible MCL patients aged 18–65 receiving ibrutinib-based frontline therapy, this is the first phase 3 OS signal supporting ibrutinib. Equally important: it makes the morbidity of ASCT hard to justify when ibrutinib alone achieves comparable survival. Guideline committees will need to address this directly.
| Arm | Regimen | Key outcome vs. Arm A |
|---|---|---|
| A (control) | R-CHOP/R-DHAP + ASCT | Reference |
| B | Ibrutinib + R-CHOP/R-DHAP + ASCT | FFS ↑, OS ↑ |
| C | Ibrutinib + R-CHOP/R-DHAP, no ASCT | FFS non-inferior to B, OS comparable to B |
Author affiliation: European Mantle Cell Lymphoma Network (multi-centre, Europe).
2. SCORPIO-PEP: ensitrelvir cuts household COVID transmission by ~67%
Journal: New England Journal of Medicine (IF ~96) · Phase 3 RCT · Published 13 May 2026 · PubMed 42127390
Study design: Double-blind, randomized, placebo-controlled trial. SARS-CoV-2–negative household contacts of a confirmed COVID-19 index case were randomly assigned to 5-day oral ensitrelvir (a 3C-like protease inhibitor, approved in Japan as Xocova) or placebo within 72 hours of symptom onset in the index patient.3
Key results: Symptomatic COVID-19 developed in ~3% of contacts receiving ensitrelvir vs. ~9% in the placebo group by day 10 — a relative risk reduction exceeding two-thirds. Adverse event rates were similar in both groups (15.1% ensitrelvir vs. 15.5% placebo).4
Peer-review status: Published in NEJM; fully peer-reviewed.
Clinical implication: This is the first phase 3 RCT to establish oral antiviral post-exposure prophylaxis as a viable strategy for COVID-19. The 72-hour window mirrors PEP protocols for HIV and influenza. Ensitrelvir is currently approved only in Japan; this trial will add pressure for regulatory submissions in the US and EU, and positions the drug for household and institutional outbreak settings.
Author affiliation: Shionogi-sponsored trial; international sites. Lead investigators from Japan.
3. Prophylactic tranexamic acid in placenta praevia CS: a 15% drop in PPH
Journal: The BMJ (IF ~105) · Phase 3 RCT · Published 13 May 2026 · PubMed 42128454 · DOI 10.1136/bmj-2026-089636
Study design: Multicentre, double-blind, randomized, placebo-controlled phase 3 trial. Women with placenta praevia undergoing caesarean section were randomized to prophylactic IV tranexamic acid (TXA) or placebo prior to incision.5
Key results: Prophylactic TXA reduced the incidence of postpartum haemorrhage compared with placebo. No maternal deaths, myocardial infarctions, seizures, or renal impairment requiring treatment were observed in either group, supporting an acceptable safety profile. The 15% relative reduction in PPH incidence aligns with secondary TXA literature in other high-risk obstetric settings.6
Peer-review status: Published in The BMJ; fully peer-reviewed.
Clinical implication: Placenta praevia carries a baseline PPH risk of 50–70% in some cohorts. A confirmed prophylactic benefit from TXA — with no added thromboembolic or neurological signal in this trial — gives obstetricians and anaesthetists a concrete protocol addition for this high-risk group. International obstetric societies are likely to incorporate this into guidance on CS-PPH prevention.
Author affiliation: First author: Lizi Wu (affiliation not confirmed in accessible records); multicentre trial, multiple sites.
4. Psilocybin for MDD: rapid remission from a single dose, effects persisting past 3 months
Journal: JAMA Network Open (IF ~13.8) · Phase 2 RCT · Published 15 May 2026 · DOI 10.1001/jamanetworkopen.2026.12589
Study design: Randomized, double-blind, placebo-controlled phase 2 trial at Karolinska Institutet (Sweden). Thirty-five adults aged 20–65 with moderate-to-severe recurrent MDD were randomized to a single 25 mg psilocybin dose or active placebo (niacin). All received 5 sessions of psychotherapeutic support. Outcomes were assessed by blinded physicians.7
Key results (primary endpoint: MADRS change at day 8):
- Psilocybin group: −9.7 points on MADRS
- Placebo group: −2.4 points
- Between-group difference: 7.3 points (statistically significant, clinically meaningful)
- Antidepressant effect detectable by day 2 on self-report
- Remission at 6 weeks: 53% psilocybin vs. 6% placebo
- At 1 year, 53% of the psilocybin group remained in remission (no confirmed group difference vs. placebo at that point, as many placebo participants had recovered by then)
Some participants required additional support after dosing due to anxiety.8
Peer-review status: Published in JAMA Network Open; fully peer-reviewed.
Clinical implication: A 7.3-point MADRS difference at day 8 from a single dose, with 53% remission at six weeks, outperforms the response curves seen in most SSRI and SNRI trials at equivalent time points. The absence of confirmed 1-year group difference leaves open whether the psilocybin benefit is durable independent of placebo convergence over time. Trial size (n=35) limits generalization; the authors flag repeated dosing and adjunctive strategies as the next questions.
Author affiliation: Hampus Yngwe (lead, PhD student) and Johan Lundberg (PI, professor), Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
5. Semaglutide for AUD + obesity: heavy drinking days drop 41% vs. 26% on placebo
Journal: The Lancet (IF ~168) · Phase 3 RCT · Published May 2026 · DOI 10.1016/S0140-6736(26)00305-3
Study design: Single-centre, double-blind, randomized, placebo-controlled trial at Copenhagen University Hospital. 108 adults with comorbid obesity (BMI ≥30) and alcohol use disorder were randomized to once-weekly subcutaneous semaglutide (titrated to 2.4 mg) or placebo over 26 weeks. All participants received up to 10 sessions of CBT focused on motivation, craving, and relapse prevention.9
Key results (primary endpoint: heavy drinking days at 26 weeks):
- Semaglutide: −41.1 percentage points (95% CI −48.7 to −33.5)
- Placebo: −26.4 percentage points (95% CI −34.1 to −18.6)
- Between-group difference: −13.7 pp (95% CI −22.0 to −5.4; p = 0.0015)
- 81% of participants completed the trial
- Secondary: semaglutide group lost −11.2 kg vs. −2.2 kg in placebo; alcohol craving, total consumption, and biomarkers all showed greater improvement10
Peer-review status: Published in The Lancet; fully peer-reviewed.
Clinical implication: The 13.7-point between-group difference in heavy drinking days is comparable to or better than every currently FDA-approved pharmacotherapy for AUD (naltrexone, acamprosate, disulfiram). Semaglutide's dual effect on drinking and weight is mechanistically coherent — GLP-1 receptors modulate dopaminergic reward pathways — but the single-centre design, the all-CBT background, and a population with comorbid obesity limit direct generalizability to leaner or untreated AUD patients. The funding chain (Novo Nordisk Foundation among others) is relevant context. Multi-site replication is the obvious next step.
Author affiliation: Mette Kruse Klausen (lead), Copenhagen University Hospital, Copenhagen, Denmark. Funded in part by the Novo Nordisk Foundation, Research Foundation — Mental Health Services (Capital Region of Denmark), and others.
References
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- 2TRIANGLE trial 4.5-year follow-up Instagram summary
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