Five PubMed papers for July 21–28: bladder-cancer survival leads

The highest-priority paper in the July 21–28 PubMed entry-date window is a phase 3 bladder-cancer trial: perioperative enfortumab vedotin plus pembrolizumab improved two-year event-free and overall survival over cisplatin-gemcitabine, while increasing grade 3 or higher adverse events. 1

The ranking is an early triage order, not a mature citation leaderboard. OpenAlex reported one cited-by work for the NEJM paper and zero for the other four finalists when checked on July 28. Because these papers are only days old, journal tier, trial design, sample size, and direct clinical utility break the ties. 23456

PubMed exposes entry dates at day granularity for these records, so the boundary is date-based rather than a claim about a precise hour. The search focused on original human medical research in high-impact journals; it was not a citation-complete sort of every record in PubMed.

The current numeric Journal Impact Factor was not consistently retrievable from the official journal pages in this pass. The accessible official metrics list Nature Medicine at 52.5 for 2025 and The BMJ at 42.7; NEJM, JAMA, and The Lancet Neurology are therefore labeled by impact tier rather than assigned an unverified number. 1112

Design and population. KEYNOTE-B15/EV-304 was an open-label phase 3 randomized trial in adults with cisplatin-eligible muscle-invasive bladder cancer. The perioperative arm assigned 405 participants to four cycles of enfortumab vedotin plus pembrolizumab before cystectomy, followed by adjuvant enfortumab vedotin and pembrolizumab. The comparator assigned 403 participants to neoadjuvant cisplatin-gemcitabine and cystectomy. The primary endpoint was event-free survival; overall survival and pathological complete response were key secondary endpoints. 1

Primary result. At two years, estimated event-free survival was 79.4% with enfortumab vedotin plus pembrolizumab versus 66.2% with cisplatin-gemcitabine, HR 0.53 (95% CI 0.41–0.70; P<0.001). Overall survival was 86.9% versus 81.3%, HR 0.65 (95% CI 0.48–0.89; P=0.006). Pathological complete response was 55.8% versus 32.5% (P<0.001). The trade-off was toxicity: grade 3 or higher adverse events occurred in 75.7% versus 67.2%. 1

Evidence strength and limitation. The survival endpoints and randomized comparison make this the most practice-facing result in the set. It is still a multi-component perioperative regimen rather than a clean test of one drug, and 86.7% of participants in the experimental arm and 89.6% in the control arm underwent cystectomy. More grade 3 or higher toxicity means the efficacy gain cannot be separated from treatment intensity when clinicians assess individual fitness and competing risks. 1

Clinical implication. For cisplatin-eligible patients with muscle-invasive bladder cancer who can tolerate the regimen, the trial supports discussing perioperative enfortumab vedotin plus pembrolizumab as a survival-improving alternative to cisplatin-gemcitabine. The decision still turns on adverse-event risk and the feasibility of completing surgery and adjuvant treatment, not on pathological response alone.

Affiliation and funding. First author Matthew D. Galsky is affiliated with Mount Sinai Tisch Cancer Center and the Icahn School of Medicine at Mount Sinai. The abstract reports funding from Merck Sharp & Dohme and others; the author list also includes employees of Pfizer, Astellas, and Merck. 1

Read the full paper in NEJM.

Design and population. TEMPLE was a phase 3b, double-dummy, randomized active-controlled trial across 12 countries. It randomized 545 adults with at least four migraine days per month to atogepant 60 mg once daily or topiramate at the highest tolerated dose of 50, 75, or 100 mg per day. The blinded comparison lasted 24 weeks, followed by a 52-week open-label period. 7

Primary result. Discontinuation because of treatment-emergent adverse events was 12% with atogepant versus 30% with topiramate, RR 0.4 (95% CI 0.3–0.6; P<0.0001). Atogepant also produced a higher rate of at least a 50% reduction in mean monthly migraine days, 64% versus 39%, RR 1.6 (95% CI 1.4–2.0; P<0.0001). The least-squares mean reduction in monthly migraine days was 6.3 versus 4.5, a between-group difference of 1.8 days (95% CI 1.0–2.5; P<0.0001). Treatment-related adverse events occurred in 56% versus 78%. 7

Evidence strength and limitation. A direct comparison is more useful than another placebo-controlled efficacy study when both drugs are already established options. The main blinded result lasts six months, while the longer follow-up is open label. The safety population was 89% female and 96% White, and AbbVie funded the study; one serious adverse event, an anaphylactic reaction, was considered treatment-related in the atogepant group. 7

Clinical implication. For patients who need an oral preventive and have struggled with topiramate's tolerability, TEMPLE gives clinicians a quantitative reason to prioritize atogepant when access and contraindications permit. The result is less about a new efficacy ceiling than about the practical fact that a preventive drug cannot work if patients stop taking it.

Affiliation and funding. First author Uwe Reuter is affiliated with Charité Universitätsmedizin Berlin and University Hospital Bonn. AbbVie funded the study; an author was affiliated with AbbVie. 7

Read the full paper in The Lancet Neurology.

Design and population. DISCOUNT was a randomized clinical trial at 22 French stroke centers. Adults with acute ischemic stroke from a primary, isolated medium or distal vessel occlusion were assigned to thrombectomy plus medical treatment or medical treatment alone. The planned enrollment was 488, but the trial stopped after interim review for futility and a higher rate of symptomatic intracranial hemorrhage. The final randomized population was 244, with 217 completing follow-up. 8

Primary result. At three months, a good functional outcome, defined as modified Rankin Scale 0–2, occurred in 62% with thrombectomy versus 68% with medical treatment alone, OR 0.73 (95% CI 0.40–1.31; P=0.29). Among the 100 participants who actually received thrombectomy, symptomatic intracranial hemorrhage occurred in 11% versus 3% in those who did not receive the procedure (P=0.008); subarachnoid hemorrhage was 13% versus 2% (P<0.001), and embolus migration was 5% versus 1% (P=0.04). Mortality was 6% versus 8% (P=0.49). 8

Evidence strength and limitation. This is a negative randomized trial with a safety signal, not evidence that thrombectomy has no role in every distal occlusion. Early stopping limits precision, and the result applies to the trial's imaging, occlusion, time-window, and medical-treatment criteria. The procedural complication comparison is reported by treatment received, whereas the functional endpoint is reported by randomized group, so the estimands should not be blended.

Clinical implication. DISCOUNT does not support routine extension of thrombectomy to this MDVO population on the basis of vessel occlusion alone. For stroke teams, the paper shifts the question toward patient selection and procedural risk rather than assuming that the benefit established for proximal large-vessel occlusion transfers distally.

Affiliation and funding. First author Frédéric Clarençon is affiliated with AP-HP, Sorbonne Université, and Hôpital Pitié-Salpêtrière in Paris. The PubMed abstract does not state a funder. 8

Read the full paper in JAMA.

Design and population. STOP-HS1 and STOP-HS2 were identically designed, randomized, double-blind, placebo-controlled phase 3 trials of the oral selective JAK1 inhibitor povorcitinib. Adults with moderate-to-severe hidradenitis suppurativa were randomized to 45 mg, 75 mg, or placebo, with placebo groups crossing over at week 12. The primary endpoint was HiSCR50 at week 12, defined as at least a 50% reduction in abscess and inflammatory-nodule count without an increase in abscess or draining-tunnel count. The trials enrolled 608 and 619 patients. 9

Primary result. In STOP-HS1, HiSCR50 was reached by 40% with 45 mg, 41% with 75 mg, and 30% with placebo. The corresponding odds ratios were 1.6 (95% CI 1.1–2.5; P=0.0240) and 1.6 (95% CI 1.1–2.4; P=0.0214). In STOP-HS2, the rates were 42%, 42%, and 29%, with odds ratios 1.8 (95% CI 1.2–2.8; P=0.0035) and 1.9 (95% CI 1.2–2.8; P=0.0033). Serious treatment-emergent adverse events occurred in 1–2% of povorcitinib-treated patients and 2–3% of placebo patients through week 12; by week 54, serious adverse events occurred in 5% and 6% of those receiving 45 mg and 75 mg. 9

Evidence strength and limitation. Replication across two phase 3 trials is the main strength. HiSCR50 is a meaningful response threshold, but it is not remission, and the week-12 placebo comparison gives way to crossover for longer-term assessment. Acne, nasopharyngitis, and upper-respiratory infection were among the most frequent adverse events; one death of undetermined etiology was judged unrelated to treatment. 9

Clinical implication. The trials support povorcitinib as an oral efficacy option for moderate-to-severe hidradenitis suppurativa, especially when injectable treatment is unsuitable or unwanted. Its place in sequencing will depend on longer safety follow-up, monitoring requirements, and comparison with established biologic strategies.

Affiliation and funding. First author Martina L. Porter is affiliated with Harvard Medical School and Beth Israel Deaconess Medical Center. The author list includes an Incyte Corporation affiliation, but the PubMed abstract does not provide a consolidated funding statement. 9

Read the full paper in Nature Medicine.

Design and population. This BMJ study emulated a target trial using data from 36 US hospitals. It included 1,276 adults with active hematological malignancy or solid tumor with metastases, high tumor burden, or laboratory and clinical features consistent with tumour lysis syndrome. Early treatment meant rasburicase within 12 hours of TLS onset; 705 patients received it. Logistic regression with inverse-probability-of-treatment weighting addressed measured differences between groups. 10

Primary result. The composite of acute kidney injury requiring kidney replacement therapy or death during the index admission occurred in 32.7% of patients treated early versus 42.0% without early treatment, adjusted OR 0.67 (95% CI 0.52–0.88; P<0.001). The 90-day mortality sensitivity analysis was directionally consistent, adjusted OR 0.71 (95% CI 0.54–0.94). Patients treated early had higher median uric acid before weighting, 11.9 versus 9.9 mg/dL, but measured illness severity was balanced after weighting. 10

Evidence strength and limitation. The multicenter design and explicit target-trial framework make this more informative than an uncontrolled case series. It remains observational: treatment timing was not randomized, and inverse-probability weighting cannot remove unmeasured confounding. The result should therefore be read as an association that supports a randomized timing study, not as proof that early rasburicase caused the lower event rate.

Clinical implication. For oncology and nephrology teams, the result supports treating recognition of TLS as a time-sensitive protocol decision rather than waiting for kidney injury to declare itself. It does not settle which patients with borderline or evolving TLS should receive rasburicase, where adverse effects and cost also matter.

Affiliation and funding. First author Tushar Shenoy is affiliated with the Division of Renal Medicine at Brigham and Women’s Hospital; the author group includes Harvard, Stanford, Yale, and other US centers. The PubMed record does not state a funder. 10

Read the full paper in The BMJ.

The strongest common signal is methodological rather than disease-specific: clinical usefulness depends on the comparator and the harm profile as much as on response. The NEJM and TEMPLE trials pair efficacy with a direct treatment alternative and make toxicity part of the decision. STOP-HS1/2 shows why replication across two phase 3 trials matters, while DISCOUNT demonstrates that a technically feasible procedure can fail its functional endpoint and add harm. The BMJ study offers a clinically plausible timing signal, but its observational design sets a lower ceiling on causal confidence.

For a quick reading order, start with KEYNOTE-B15/EV-304 if bladder-cancer treatment selection is relevant; read TEMPLE for oral migraine-prevention tolerability; read DISCOUNT before extending thrombectomy to MDVOs; read STOP-HS1/2 for the HS treatment pipeline; and use the rasburicase paper to examine how a target-trial emulation can inform, but not replace, randomized evidence.