Prehabilitation programs are increasingly recognized for their potential to improve surgical outcomes. However, their efficacy remains debated, largely due to a lack of pathophysiologically driven implementation and limited personalization. To determine the impact of personalized vs standard prehabilitation on preoperative physical, cognitive, and immune function and postoperative outcomes. In this prospective, single-blinded, randomized interventional trial conducted from June 2020 to September 2022 in a single academic medical center, 58 patients undergoing major elective surgery were randomized to standard (n = 30) or personalized prehabilitation (n = 28) using block randomization. Those with contraindication to exercise, an American Society of Anesthesiologists score 4 or higher, in palliative care, less than 14 days between screening and surgery were excluded. Data were analyzed from April 2023 to May 2025. The personalized group received 2 weekly one-on-one remote coaching sessions tailored to individual progress in 4 domains (physical activity, nutrition, cognitive training, and mindfulness), whereas the standard group followed a paper-based program, including the same domains, without individualized support. Primary clinical outcomes included cognitive assessments and physical performance measures, including the wall squat test, timed-up-and-go test, and 6-minute walk test (6MWT). The primary immunological outcomes included major innate and adaptive immune cell frequencies and intracellular signaling responses measured using a 47-plex mass cytometry immunoassay. Of 58 patients (median [IQR] age, 57 [45-67] years; 31 [57%] female) enrolled, 54 completed the study (n = 27 per group). The personalized group exhibited significant improvements in physical measures (eg, median [IQR] 6MWT: 496 [340-619] minutes before prehab versus 546 [350-728] minutes after; P = .03) and fewer moderate-to-severe postoperative complications (4 vs 11 Clavien-Dindo grade >1; P = .04). Multivariable modeling identified profound and cell-type specific immune alterations postprehabilitation compared to baseline (area under the receiver operating characteristic curve [AUROC], 0.88; 0.79-0.97; P < .001; leave-one-out cross-validation), including dampened phosphorylated protein kinase R-like endoplasmic reticulum kinase 1/2 signaling in classical monocytes and myeloid-derived suppressor cells after interleukin 2, 4, and 6 stimulation, and reduced phosphorylated cyclic adenosine monophosphate response–element binding protein signaling in Th1 cells. In contrast, the standard group showed only moderate clinical improvements and no immune changes (AUROC = 0.63; 95% CI, 0.48-0.78; P = .12). In this study, personalized prehabilitation significantly altered the immunome before surgery, dampening inflammatory signaling responses previously implicated in the pathophysiology of key surgical outcomes, including surgical site infections and postoperative neurocognitive decline. These changes were accompanied by improved physical and cognitive function before surgery and decreased postoperative complications. These findings support the use of personalized prehabilitation and provide an avenue for biologically driven monitoring of prehabilitation efficacy, and individual tailoring of programs to optimize surgical readiness and recovery. ClinicalTrials.gov Identifier: NCT04498208
Per-oral endoscopic myotomy (POEM) achieves an 80–90
A 65-year-old kidney transplant recipient was admitted with isolated fever. Initial tests revealed pancytopenia and elevated C-reactive protein levels but failed to detect any pathogen. A bone marrow aspirate was performed because of signs suggestive of hemophagocytic lymphohistiocytosis, but the results were negative. The patient subsequently developed fulminant hepatitis. Liver biopsy showed severe acute cytolytic hepatitis with a neutrophil-rich infiltrate, suppurative hepatocytic necrosis, and hemophagocytosis. Etoposide, N-acetylcysteine, and piperacillin-tazobactam were initiated. However, the patient died from hemorrhagic complications of the biopsy. Posthumous shotgun metagenomics on liver samples identified Spiroplasma ixodetis.
The impact of high-efficacy therapies (HET) on progression independent of relapse and MRI activity (PIRMA) remains poorly defined. In this context, using the French MS registry, we aimed to assess the real-life effectiveness of HET compared with moderate-efficacy therapies (MET) on PIRMA in patients with relapsing-onset multiple sclerosis. Data were collected from patients with relapsing-onset multiple sclerosis of the French MS registry, between January 2010 and June 2023, with a mean follow-up of 3.7 years. Patients with relapsing-onset multiple sclerosis were included in the analysis if they were treated first with HET (2666 included) or MET (7833 included) and had expanded disability status scale and MRI follow-up every 2 years. Each outcome was studied using a propensity score framework. The primary outcome was time to first PIRMA. Secondary outcomes were PIRMA incidence, time to first confirmed disability progression, relapse-associated worsening (RAW), MRI-associated worsening (MAW) and identification of risk factors associated with PIRMA. A total of 10 499 patients fulfilled the inclusion criteria. The mean and standard deviation (SD) age at treatment initiation was 36.4 (10.3) years, with a mean (SD) disease duration of 3.1 (5.1) years. The restricted mean (SD) survival time to first PIRMA was slightly, but significantly shorter in the HET group compared with the MET group [8.7 (0.08) versus 8.9 (0.05) years, P = 0.017]. However, when looking at time to first confirmed disability progression, it tend to be longer in the HET group compared with the MET group [7.6 (0.10) versus 7.3 (0.06) years, P = 0.071], and it was probably linked to the shorter time to first RAW and MAW in the MET group [9.2 (0.06) versus 8.7 (0.05) years, P < 0.001 for RAW; and 9.0 (0.05) versus 8.5 (0.07) years, P < 0.001 for MAW]. Baseline risk factors associated with increased PIRMA incidence in the whole population were high expanded disability status scale, higher age at baseline and the presence of spinal cord lesions. Even if HET gives better control on disability accumulation related to disease activity than MET, our real-life study suggests that PIRMA-related mechanisms are not differentially affected by HET versus MET.
Diffuse large B-cell lymphoma (DLBCL) poses a challenge in hematology given its varied symptoms, and the complex interplay between disease and treatment effects on health-related quality of life (HRQoL). The phase 3 POLARIX study demonstrated superior progression-free survival and a similar safety profile with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with previously untreated DLBCL. Here, we evaluate HRQoL through patient-reported outcome (PRO) instruments to fully characterize the patient experience in the POLARIX study. Changes from baseline in HRQoL, lymphoma symptoms, and gastrointestinal (GI) symptoms were assessed, as well as incidence and severity of common symptoms by PROs vs clinician-reported adverse events (AEs). Baseline characteristics of PRO-evaluable patients (N = 874) were consistent. Comparison between PROs and clinician-reported AEs revealed a notable discordance; patients generally reported a higher incidence of symptoms than clinicians, emphasizing the need for patient-centric tools to accurately capture the patient experience. Both treatments exhibited rapid and sustained improvements in HRQoL and lymphoma symptoms, with the most substantial improvements seen in global health status/QoL, lymphoma symptoms, fatigue, role, emotional, and social functioning. GI symptoms (diarrhea, constipation, nausea, and vomiting) were generally similar between treatment arms and returned to baseline levels after treatment completion. These HRQoL data underscore the complementarity of PROs, as an adjunct to clinician-reported AEs, in evaluating the efficacy and tolerability of new treatments, including Pola-R-CHP, which may represent a new benchmark for patient-reported HRQoL in previously untreated DLBCL. This trial was registered at www.clinicaltrials.gov as NCT03274492.
