2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:Tb20,Abstract Patients with multiple myeloma bearing a deletion of chromosome 17p (del(17p)), mutation of TP53 , or both have poorer prognosis compared to patients without these aberrations. We investigated the activity and mechanism of melflufen (melphalan flufenamide) in myeloma models with wild type TP53 ( TP53 wt) and complete TP53 deletion ( TP53 −/− ) and assessed the efficacy of melflufen in patients with del(17p) and/or TP53 mutation. Ex vivo data from myeloma plasma cells (PC) showed comparable activity of melflufen in del(17p), TP53 −/− , and TP53 wt samples. scRNAseq data demonstrated that melflufen sensitive PCs had lower expression of p53 target genes and higher expression of genes associated with DNA damage repair and cell cycle checkpoints. Irrespective of TP53 status, melflufen induced apoptosis, DNA damage, and mitochondrial dysfunction, while only in TP53 −/− cells, it led to changes in expression of cell cycle checkpoint and apoptosis genes. Post-hoc analysis of the OCEAN trial melflufen-treated del(17p) patient population also demonstrated favorable progression free survival compared to pomalidomide-treated cohort. Our insights into the molecular mechanisms of melflufen activity in TP53 −/− myeloma support its clinical efficacy and application in the del(17p) and TP53 −/− patient population. Trial registration NCT03151811, registration 2017-05-09. 31:T561,K.A., Y.D., K.W.M., J.O., S.S.G. are employees of and receives stock or stock options from Oncopeptides. S.N. is an employee of, has participated on a data safety monitoring board or advisory board for, and receives stock or stock options from Oncopeptides. M.T. is a consultant of and receives stock or stock options from Oncopeptides. A.S., F.L., are former employees of and receive stock or stock options from Oncopeptides. F.S. has received grants or contracts from Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Targovax, and Sanofi; payment or honoraria for lectures or speakers’ bureau participation from AbbVie, Amgen, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Oncopeptides, Pfizer, Sanofi, SkyliteDX, and Takeda; serving on a data safety monitoring or advisory board for AbbVie, Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, and Takeda; and stock or stock options from Nordic Nanovector. P.So. has received grants or contracts from Amgen, Celgene, Janssen, Takeda, and SkylineDx. C.A.H. has received research funding from Oncopeptides related to this work, and from IMI2 projects HARMONY and HARMONY PLUS, WntResearch, Orion, Kronos Bio, Novartis, Celgene, Zentalis Pharmaceuticals for unrelated work, plus honoraria or personal fees from Amgen and Autolus. The remaining authors declare no competing financial interests.32:T861,A preplanned exploratory analysis of the ABC3 trial, performed in all 10 NICU centres in the Netherlands, evaluating the effect of physiological-based cord clamping (PBCC) on intact survival in very preterm infants, found a positive association between intact survival and experience with the PBCC approach. To evaluate the effect of PBCC on intact survival in preterm infants in centres with more experience with PBCC and in centres with less experience. A post-hoc secondary analysis was performed. Experienced and less experienced centres participating in the ABC3 trial included 669 infants born before 30 weeks of gestation, who were randomized to stabilization with intact cord and clamping after reaching cardiorespiratory stability (PBCC) or clamping after 30-60 s followed by stabilization (time-based delayed cord clamping (TBCC)). Centres were defined as "experienced" when: (1) caregivers were trained in the PBCC approach with evaluation of video and RFM recording; (2) experience in previous studies; (3) early initiation of ABC3 and (4) ≥20 % of inclusions. The primary outcome was intact survival (survival without major cerebral injury and/or necrotizing enterocolitis (NEC)). Outcomes were adjusted for differences in baseline characteristics. Two centres were classified as "experienced" and the other eight as "less-experienced", and included 43.1 % and 56.9 % of infants respectively. In experienced centres, intact survival was higher after PBCC compared with TBCC (72 % vs. 59 %; aOR 1.93 (95 %CI 1.73-2.17, P < 0.001)), with lower mortality (10 % vs. 20 %; aOR 0.40 (95 % CI 0.25-0.63, P < 0.001)). In less experienced centres, intact survival was not different (72 % vs. 75 %; aOR 0.94 (95 % CI 0.64-1.39, P = 0.93)), with higher mortality (16 % vs. 9.1 %; aOR 1.92 (95 % CI 1.05-3.50, P = 0.03)). PBCC was associated with increased intact survival in centres that had more previous experience and exposure to PBCC, but not in centres with less experience. We recommend that the effect of experience and training for new approaches should be taken into consideration in future studies on PBCC.33:Td36,Prediabetes is associated with increased risk of cardiovascular disease and heart failure. Multicomponent lifestyle interventions, including diet and physical activity targeting weight loss are recommended for prediabetes management, although their long-term impact on cardiovascular outcomes remains unclear. Reaching prediabetes remission by restoring normal glucose regulation has been shown to profoundly reduce future type 2 diabetes risk outlasting the time of lifestyle intervention. We aimed to investigate whether prediabetes remission is associated with a lower incidence of cardiovascular death or hospitalisation for heart failure compared with non-remission, with a long-term legacy effect. Post-hoc analyses were performed from two landmark diabetes prevention trials, the US Diabetes Prevention Program Outcomes Study (DPPOS) and the Chinese DaQing Diabetes Prevention Outcomes Study (DaQingDPOS). Remission was assessed using the American Diabetes Association criteria after 1 year (DPPOS) or 6 years (DaQingDPOS) of intervention. The primary endpoint was cardiovascular death or hospitalisation for heart failure over 20 and 30 years, respectively. In DPPOS, inverse probability of treatment weighting adjusted for baseline differences. A unifying meta-analysis was calculated across both data sets for the primary endpoint and all-cause mortality. For DPPOS, follow-up time is reported from the start of the original Diabetes Prevention Program trial, July 31, 1996, to the end of DPPOS phase 3, Feb 23, 2020. In total, 2402 participants were included in DPPOS and 540 in DaQingDPOS. In DPPOS, 275 (11·5%) of 2402 participants reached remission after 1 year of intervention compared with 2127 (88·5%) of 2402 not reaching remission. In DPPOS, after a median follow-up of 20 years, the event rate for cardiovascular death or hospitalisation of heart failure was 1·74 (95% CI 0·87-3·48) per 1000 person-years in participants who reached remission versus 4·17 (95% CI 3·55-4·89) in those without remission (p=0·013) with a fully adjusted hazard ratio of 0·41 (95% CI 0·20-0·84; p=0·014). Results remained robust after adjustment, were confirmed in DaQingDPOS (primary endpoint: HR 0·49 [95% CI 0·28-0·84]; p=0·010), and were supported by a pooled meta-analysis. Results were stable when analysing the composite endpoint in those reaching remission at least once during follow-up, with a HR of 0·43 (0·29-0·63; p<0·0001). Reaching prediatbetes remission is linked to a decades-long benefit, halving the risk of cardiovascular death or hospitalisation for heart failure in diverse populations. Targeting remission might represent a new approach to cardiovascular prevention. German Center for Diabetes Research via the German Federal Ministry of Research, Technology and Space; Ministry of Science, Research, and the Arts Baden-Württemberg; Helmholtz Munich; the Helmholtz Young Investigators Groups funding programme; the Cluster of Excellence EXC-2124; and the German Research Foundation (DFG). For DaQIng: Centers for Disease Control and Prevention, WHO, the China-Japan Friendship Hospital, and Da Qing First Hospital and Fuwai Hospital, Chinese Academy of Medical Sciences. For DPPOS: National Institute of Diabetes and Digestive and Kidney Diseases. For the German and Chinese translation of the abstract see Supplementary Materials section.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Post-hoc Analysis: study design Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Post-hoc Analysis (study design). Clinician-written summaries and actionable practice insights. 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latest HUS study permit HUS/395/2018 dated 13 February 2018; Permit numbers 239/13/03/00/2010, 303/13/03/01/2011) and in accordance with the Declaration of Helsinki."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"},"order":3,"value":"Not applicable."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":4,"value":"$31"}],"deposited":{"date-time":"2025-12-23T13:25:49Z","timestamp":1766496349000,"date-parts":[[2025,12,23]]},"issn-type":[{"type":"electronic","value":"2162-3619"}],"published":{"date-parts":[[2025,12,23]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":"10.3390/ijms21010013","key":"729_CR1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Ho T, Tan BX, Lane D. How the other half lives: what p53 does when it is not being a transcription factor. Int J Mol Sci. 2019;21(1).","article-title":null,"journal-title":null,"doi-asserted-by":"crossref"},{"DOI":"10.1200/JCO.2015.61.2267","key":"729_CR2","year":"2015","issue":"26","author":"A Palumbo","volume":"33","first-page":"2863","unstructured":"Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised international staging system for multiple myeloma: A report from international myeloma working group. J Clin Oncol. 2015;33(26):2863–9.","article-title":null,"journal-title":"J Clin Oncol","doi-asserted-by":"publisher"},{"DOI":"10.1182/blood.2020008346","key":"729_CR3","year":"2021","issue":"9","author":"J Corre","volume":"137","first-page":"1192","unstructured":"Corre J, Perrot A, Caillot D, et al. del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma. 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The study was industry funded with multiple authors employed by the sponsor, which may bias analyses.","practice_takeaway":"For RRMM with del(17p), melflufen+dexamethasone yielded longer PFS and higher ORR than pomalidomide+dexamethasone in a post‑hoc analysis; preclinical work showed activity irrespective of TP53 status. Apply cautiously given the subgroup design and funding-related bias risk."}},{"doi":"10.1016/j.resuscitation.2025.110921","pmid":"41419025","title":"Experience with physiological based cord clamping is associated with increased effect size: a post-hoc analysis of the ABC3 trial","journal_title":"Resuscitation","journal_issn":"0300-9572","published_at":"2025-12-20T00:00:00.000Z","url":"https://doi.org/10.1016/j.resuscitation.2025.110921","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-21","doi":"10.1016/j.resuscitation.2025.110921","days":"30","issn":"0300-9572","rank":"10","field":"Clinical Medicine","score":"8","category":"Emergency Medicine","categories":["Emergency Medicine"],"_categories":["Emergency Medicine"]},"pubmed":{"doi":"10.1016/j.resuscitation.2025.110921","title":"Experience with physiological based cord clamping is associated with increased effect size: a post-hoc analysis of the ABC3 trial.","journal":"Resuscitation","methods":"","results":"Two centres were classified as \"experienced\" and the other eight as \"less-experienced\", and included 43.1 % and 56.9 % of infants respectively. 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remission status was not randomized.","value_numeric":null}],"summaries":{"what_studied":"Post-hoc analyses of two diabetes prevention cohorts tested whether remission of prediabetes (ADA criteria) lowers cardiovascular death or heart‑failure hospitalization versus no remission. Remission was assessed after 1 year in DPPOS (n=2402) and after 6 years in DaQingDPOS (n=540), with outcomes tracked ~20 and ~30 years, respectively.","key_result":"In DPPOS, 275/2402 (11.5%) achieved remission at 1 year; the composite event rate was 1.74 vs 4.17 per 1000 person‑years for remission vs non‑remission (p=0.013), with an adjusted HR 0.41 (95% CI 0.20–0.84; p=0.014). DaQingDPOS showed a similar association (HR 0.49, 95% CI 0.28–0.84; p=0.010); pooled analysis supported these findings, and achieving remission at least once during follow‑up was linked to HR 0.43 (0.29–0.63; p<0.0001).","limitations":"These are post‑hoc comparisons of remission vs non‑remission, not randomized groups, with inverse probability weighting only in DPPOS. Remission timing differed between cohorts (1 year vs 6 years), which may add heterogeneity.","practice_takeaway":"Achieving prediabetes remission was associated with about half the risk of cardiovascular death or heart‑failure hospitalization over decades. Targeting remission of prediabetes may be a reasonable clinical goal aligned with lifestyle care."}}],"initialOffset":3,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"study_design","value":"Post-hoc Analysis"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Study Designs","href":"/hub/tag/study_design"},{"name":"Post-hoc Analysis"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"study_design","hub_tag_value":"Post-hoc Analysis"}}}]]

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