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Table of contents S1 Criteria for exercises selection in subjects with low back pain Alessandro Aina S2 Recent advances in pathophysiology and treatment of myofascial trigger points Marco Barbero S3 Rehabilitation of scapular dyskinesia Barbara Cagnie S4 Musculoskeletal rehabilitation in subjects affected by neurological disorders Elena Castelli S5 Which examination tests suggest the best candidates for manual therapy Chad Cook S6 Case study: the role of the measurements for the identification of targets and guidance of the treatment Silvano Ferrari S7 Assessment of joint mobility: state of the art Andrea Foglia, Paolo Bizzarri S8 Core stabilization exercises in the treatment of urinary incontinence Donatella Giraudo S9 Preventing surgical subacromial decompression through rotator cuff rehabilitation Chris Littlewood S10 Methodological aspects of Clinical Prediction Rules in the rehabilitation of Low Back Pain Paolo Pillastrini S11 Interpretability of outcome measures in musculoskeletal rehabilitation Daniele Piscitelli S12 Conservative treatment of the misalignment of the spine: state of the art and perspectives Michele Romano S13 Balance training in subjects with musculoskeletal disorders Andrea Tettamanti S14 Dosage of manual therapy: principles for clinical practice Carla Vanti S15 Are there speed limits in post-surgery lower limb rehabilitation? Stefano Vercelli S16 Classification of predominant neuropathic, nociceptive or central sensation pain Lennard Voogt P1 A wearable proprioceptive stabilizer (Equistasi®) for rehabilitation of balance disorders in multiple sclerosis patients: preliminary results of a randomized, double-blind, versus placebo controlled study Aceto Maria, Spina Emanuele, Paone Paolo, Silvestre Francesco, Carotenuto Antonio, Cerillo Ilaria, Orefice Giuseppe P2 Effect of repeated neck retraction movements on strength and EMG activity of the upper limbs, range of motion and cervical posture Bassi Raffaele, Fiorito Serena, Aina Alessandro P3 Hamstring injuries: clinical assessment or image evaluation? Bonfanti M., Pasquetti M. P4 Effectiveness of the physical therapy treatment on pelvic floor muscles in pelvic girdle pain. A literature review Bortolami Arianna, Pillastrini Paolo, Vanti Carla P5 Scapulo-humeral muscles electromiographic activity during the elevation movement of the upper limb in subjects with rotator cuff lesion Brioschi D, Vitali M, Pedretti A, Fraschini G, Tettamanti A P6 Mechanical low back pain: secular trend and intervention topics of randomized controlled trials Castellini G, Gianola S, Bonovas S, Banfi G, Moja L P7 Quality of reporting in rehabilitation interventions for low back pain: a review of published randomised controlled trials Greta Castellini, Silvia Gianola, Pamela Frigerio, Michela Agostini, Rosa Bolotta, Davide Corbetta, Monica Gasparini, Paolo Gozzer, Erica Guariento, Linda Li, Valentina Pecoraro, Valeria Sirtori, Andrea Turolla, Andreano A, Lorenzo Moja P8 Power analysis and sample size reporting in rehabilitation of low back pain: review of randomized controlled trials included in Cochrane systematic review Castellini G, Gianola S, Bonovas S, Moja L P9 A core outcome set for clinical trials in non-specific low back pain Alessandro Chiarotto, Caroline B. Terwee, Maarten Boers, Raymond W. Ostelo P10 Roland & Morris Disability Questionnaire and Oswestry Disability Index: which has better measurement properties? A systematic review and meta-analysis Alessandro Chiarotto, Lara J. Maxwell, Caroline B. Terwee, George A. Wells, Peter Tugwell, Raymond W. Ostelo P11 Prevalence of myofascial trigger points in spinal pain disorders: systematic review and meta-analysis Alessandro Chiarotto, Ron Clijsen, Cesar Fernandez-de-las-Penas, Marco Barbero P12 Post-surgical scar rating scales in physiotherapy: a systematic review Ciceri Matteo, Rossetti Sara, Vercelli Stefano P13 Efficacy of action observation pre-operative training in functional recovery after hip and knee prosthesis Cislaghi M, Penone G, Marinelli G, Rezzan G, Melegati G, Gatti R P14 The use of Kinesio Taping in the treatment of hematomas: can we distinguish fancy from the effects? Colombo Claudio, Tolosa Francesca, Andrea Moriondo, Vercelli Stefano P15 Who is able to perform explicit motor imagery after stroke? Stefano Doronzio, Matteo Paci P16 Responsiveness of the Bridge tests in Symptomatic Lumbar Spondylolisthesis Silvano Ferrari, Carla Vanti, Marco Monticone P17 The relationship between number of sessions and clinical results in lumbar symptomatic spondylolisthesis Silvano Ferrari, Carla Vanti, Marco Monticone P18 Conservative treatments for upper extremity tendinopathies in occupational medicine: narrative review Garzonio Fabiola, Zanetta Anna, Bargeri Serena, Cerone Giorgia, Sartorio Francesco P19 The time-related effect of roller-massager on extensibility of the hamstring muscles Filippo Ghirlanda, Alessandro Schneebeli, Corrado Cescon, Marco Barbero P20 Effect of two different exercise programs on pain, disability and quality of life in people with subacute and chronic nonspecific neck pain Gioia G, Faccendini S, Aina A, Tettamanti A P21 A bridge between clinical practice and research: how health professionals can study literature and learn on the job Granzotto G, Coppola L, Gava I, Frassinelli M, Gattinoni F P22 Walking capacity improves after neuromotor physiotherapy in stroke patients Lorenzo Guidotti, Marco Postiglione, Bruna Lombardi, Matteo Paci P23 Intra and inter-session reliability of the angle between pain onset and submaximal pain during upper limb neurodynamics test 1: a study in healty individuals Diego Leoni, Davide Storer, Roberto Gatti, Michele Egloff, Marco Barbero P24 Effects of an AO-MI training on balance task in patients affected by multiple sclerosis Magno Tiziano, Tettamanti Andrea P25 Outcomes of treatment with neuromuscular stimulator for chronic anterior knee pain: a clinical case Daniele Maremmani, Sebastiano Cencini, Giuseppe Plebani P26 Consistency in locating pressure stimuli over the lumbar spine on a digital body chart: a comparison between chronic low back pain patients and healthy subjects Federica Moresi, Marco Barbero, Matteo Isnardi, Alberto Gallace, Corrado Cescon, Roberto Gatti P27 Malignant Cord Compression in the thoraco-lumbar spine. Early signs and symptoms in the differential diagnosis of low back pain Moretti N, Maselli, Testa M. P28 End growth results of exercise treatment to avoid bracing in adolescents with idiopathic scoliosis: a prospective cohort controlled study Stefano Negrini, Sabrina Donzelli, Francesco Saveri, Alessandra Negrini, Silvana Parzini, Michele Romano, Fabio Zaina P29 Reliability of the Ashworth scale and its modified versions: systematic review and meta-analysis Leonardo Nesi, Francesco Ferrarello, Valeria Anna Maria Bianchi, Matteo Paci P30 Differences in motor recovery between upper and lower limbs in stroke subtypes Matteo Paci, Luca Nannetti, Bruna Lombardi P31 Influence of clinical experience on the reliability of the Salford Gait Tool Giuditta Mini, Mariangela Marchettini, Francesco Ferrarello, Matteo Paci P32 A somatosensory discrimination training induces brain functional changes in healthy young subjects Fabio Piccolo, Federica Agosta, Elisabetta Sarasso, Paola Adamo, Federico Temporiti, Andrea Falini, Roberto Gatti, Massimo Filippi P33 Effects of dynamic tilt-table with integrated robotic stepping associated with functional electrical stimulation: a cross-over study Daniele Piscitelli, Roberto Meroni, Leonardo Pellicciari, Marco A. Mondelli, Thomas Favaron, Cesare G. Cerri, Enrico A. Tallarita P34 Manual therapy techniques in the treatment of whiplash and its associated disorders: a systematic review Ravizzotti Elisa, Vercelli Stefano P35 The Patient and Observer Scar Assessment Scale (POSAS) as a screening tool for early detection of pathologic post-surgical scars in physiotherapy Rossetti Sara, Ciceri Matteo, Vercelli Stefano P36 The anatomical basis of genetic dystonia: a multimodal MRI study Elisabetta Sarasso, Federica Agosta, Aleksandra Tomić, Silvia Basaia, Nataša Dragašević, Marina Svetel, Massimiliano Copetti, Vladimir S. Kostic, Massimo Filippi P37 The relative inclination of the end vertebrae of a scoliotic single curve can influence the results of the conservative treatment? A pilot study Francesco Saveri, Michele Romano, Matteo Mastrantonio, Alessandra Negrini, Fabio Zaina, Negrini Stefano P38 Physiotherapy for myofascial pain syndromes: reported methodological quality of randomized controlled trials indexed in the PEDro database Alessandro Schneebeli, Greta Castellini, Valentina Redaelli, Emiliano Soldini, Marco Barbero P39 Is the patellar pubic percussion test useful to diagnose only femur fractures or something else? Two case reports Segat M, Casonato O, Margelli M, Pillon S. P40 Effectiveness of new rehab method for MDI Spunton V, Fenini R, Garofalo R, Conti M P41 Toe walking and autism: cross-sectional study on clinical presentation patterns and correlation with language delay Valagussa G, Balatti V, Trentin L, Melli S, Norsi M, and Grossi E P42 Active Kyphosis Value (AKV): a new test for the evaluation of the kyphotisation mobility of the thoracic spine Massimiliano Vanossi, Francesco Saveri, Michele Romano P43 Pain Drawing and psychological distress in low back pain - systematic review and meta-analysis Carla Vanti, Sara Taioli, Ivan Gardenghi, Lucia Bertozzi, Anna Rosso, Antonio Romeo, Paolo Pillastrini P44 Responsiveness of the Oswestry Disability Index in symptomatic lumbar spondylolisthesis Carla Vanti, Silvano Ferrari, Martina Ruggeri, Marco Monticone P45 The relationship between instability tests, pain and disability in non-specific low back pain Carla Vanti, Bellini Filippo, Cristina Conti, Federica Faresin, Martina Ruggeri, Raffaella Piccarreta, Silvano Ferrari P46 Smartphone applications (apps) for physical therapists: a review Villanova Luca, Vercelli Stefano P47 A randomized controlled pilot trial of hand robotic training compared with a sensory-motor training program in post stroke patients Violini Claudia, Cenci Marco Joseph, Delconte Carmen, Pisano Fabrizio P48 Critical Illness PolyNeuroMyopathy (CIPNM): chance for a good prognosis Youssef S, Montesano M, Picardi M, De Giampaulis P, Corbo M, Pisani L. P49 The EdUReP approach plus manual therapy for the management of insertional Achilles tendinopathy: a case study Zanetta Anna, Garzonio Fabiola, Ruella Carolina, Sartorio Francesco

Cytotoxic attack particles released by CTLs and NK cells include diverse phospholipid membrane and glycoprotein encapsulated entities that contribute to target cell killing. Supramolecular attack particles (SMAPs) are one type of particle characterized by a cytotoxic core enriched in granzymes and perforin surrounded by a proteinaceous shell including thrombospondin (TSP)-1. TSP-4 was also detected in bulk analysis of SMAPs released by CTLs; however, it has not been investigated whether TSP-4 contributes to distinct SMAP types or the same SMAP type as TSP-1 and, if in the same type of SMAP, whether TSP-4 and TSP-1 cooperate or compete. Here, we observed that TSP-4 expression increased upon CD8 + T cell activation while, surprisingly, TSP-1 was down-regulated. Correlative Light and Electron Microscopy and Stimulated Emission Depletion microscopy localized TSP-4 and TSP-1 in SMAP-containing multicore granules. Superresolution dSTORM revealed that TSP-4 and TSP-1 are usually enriched in the same SMAPs while particles with single-positive shells are rare. Retention Using Selective Hooks assays showed that TSP-4 localizes to the lytic granules faster than TSP-1 and promotes its accumulation therein. TSP-4 contributed to direct CTL-mediated killing, as previously shown for TSP-1. TSP-4 and TSP-1 were both required for latent SMAP-mediated cell killing, in which released SMAPs kill targets after removal of the CTLs. Of note, we found that chronic lymphocytic leukemia (CLL) cell culture supernatants suppressed expression of TSP-4 in CTL and latent SMAP-mediated killing. These results identify TSP-4 as a functionally important component of SMAPs and suggest that SMAPs may be targeted for immune suppression by CLL., Competing Interests: Competing interests statement:M.L.D. is a co-founder and advisor of Granza Bio (https://www.granzabio.com). M.L.D. receives consulting fees. Granza Bio is a seed stage company and had no role in this paper—no funding was provided for this work and none of the co-authors are directly employed by Granza Bio. M.L.D. has 3% equity (founder’s shares) with a value of ~$20 and this will not be impacted by results of this paper. M.L.D. is a co-inventor on a patent application on proteinaceous particles-supramolecular attack particles. This paper will not impact this patent. We have made the paper available as a bioRxiv preprint with no new IP filed based on this work. https://www.granzabio.com/newsroom—This includes press releases mentioning M.L.D. as a founder. There are no public statements referring to the work in this paper other than the bioRxiv preprint—https://www.biorxiv.org/content/10.1101/2024.04.25.590546v1.

Background: Screening programmes for the detection of patients with hepatitis C virus (HCV) and positive viral load have been developed in many countries to achieve the World Health Organization's goal of HCV elimination by 2030. In Italy, a phased screening programme starting with individuals born between 1969 and 1989 has been implemented., Aim: To assess the prevalence of patients with positive viraemia identified through a universal screening campaign conducted among hospitalised patients at our centre during the calendar year 2022., Methods: All adult (aged ≥ 18 years) hospitalised patients, who participated in HCV screening from January to December 2022 were included, without any age restriction. Screening initially involved testing for anti-HCV antibodies and then patients who tested positive underwent further HCV-RNA testing., Results: A total of 10,846 samples were collected. Five hundred and thirty cases (4.8%) tested positive for HCV antibodies, and 109 (1%) tested positive for both HCV antibodies and HCV-RNA. Among patients with a positive viral load, the median [IQR] age was 62 [53-77] years, with a significant age difference between males and females (59 [48-67] vs. 78 [62-88]; Mann-Whitney U-test, p = 0.001). Eighty-four (77%) patients with a positive viral load were outside the target age range specified in the current National Recommendations for free-of-charge screening., Conclusions: The non-negligible prevalence of patients with a positive viral load among an unselected group of hospitalised patients suggests that such settings could effectively enhance screening programmes aimed at HCV elimination. Additionally, this approach may help identify patients who are not currently included in the National Recommendations., (© 2024 John Wiley & Sons Ltd.)

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease characterised by the uncontrolled proliferation of mature lymphocytes. A subset of CLL patients harbouring complex karyotype (CK) presents with poor prognosis and limited treatment options. This review aims to discuss the current understanding of such patient subset, including its molecular landscape, diagnostic approaches, treatment modalities and emerging therapies. Furthermore, it outlines strategies for personalised management to improve clinical outcomes in this challenging patient population., (© 2025 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background/Objectives : Splenectomy leads to a high rate of remission in chronic primary immune thrombocytopenia (ITP), but its unpredictable long-term positive outcomes and that it is a irreversible surgical approach discourage clinicians and patients. The identification of predictors of response may redefine the timing of splenectomy. In this retrospective, multicentric study we aimed to investigate clinical-histological predictors of splenectomy response in ITP patients and provide an easy-to-use score to predict splenectomy response in ITP. Methods : We considered a discovery set ( n = 17) and a validation set ( n = 30) of adult ITP patients, who underwent splenectomy for refractory disease in three Italian referral centers for ITP. Results : We found that the presence of autoimmune comorbidities, daily steroid dose prior to splenectomy, age at diagnosis and age at splenectomy were significantly associated with the outcome. Variables singly associated with an adverse outcome were combined into a clinical and a clinical-pathological score, allowing us to define a "high-risk" group which accounted for about 80% of the disease relapses observed in this cohort. At the same time, a certain clinical-pathological score indicated a "high-risk" group characterized by significantly poorer outcomes. Results were confirmed in the validation cohort. Conclusions : An integrated set of clinical and histological parameters may predict the response to splenectomy in ITP patients. While these findings provide valuable insights, they were derived from a small cohort of patients and therefore require validation in larger, more diverse populations to ensure their generalizability and robustness.

Aims: The diagnosis of lymphoplasmacytic lymphoma (LPL) in the bone marrow (BM) is challenged by aberrant phenotypes and by overlapping histological features with marginal zone lymphoma (MZL). To address these issues, we (i) assessed LPL immunophenotype on a large series of BM samples, (ii) drew possible correlations between LPL phenotype and clinical/molecular data and (iii) investigated the role of new phenotypical markers in the differential diagnosis between LPL and MZL., Materials and Methods: The study retrospectively considered 81 clinically annotated LPL diagnosed at Padua University Hospital (Padua, Italy) during a 5-year period. BM findings were correlated with clinical laboratory findings and with MYD88 and CXCR4 mutational status. The obtained results were compared with a series of 77 MZL in the BM, including 46 splenic MZL (SMZL), 14 nodal MZL (NMZL) and 17 extra-nodal MZL (EMZL)., Results: The LPL cohort included 52 males and 29 females (median age at diagnosis = 71 years). Aberrant CD10 and CD5 positivity was documented in 3 of 81 (3.7%) and 13 of 81 (16.1%) cases, respectively. CD23 positivity occurred in 56 of 81 (69.1%) cases, being usually partial/focal. CD23 expression did not correlate with any specific clinical-pathological parameter. Comparison with SMZL, NMZL and EMZL highlighted less frequent splenomegaly, higher serum paraprotein, higher CD23 expression and fewer follicular dendritic cell networks in LPL. A combined clinical-pathological score supported the differential diagnosis between LPL and MZL of any type. The highest diagnostic yield was obtained for the differential diagnosis between LPL and SMZL., Conclusions: Partial positivity for CD23 is a common feature of LPL in the BM. Together with other clinical and histological parameters, CD23 expression supports the differential diagnosis between LPL and MZL., (© 2024 John Wiley & Sons Ltd.)

Finding an effective treatment for T-PLL patients remains a significant challenge. Alemtuzumab, currently the gold standard, is insufficient in managing the aggressiveness of the disease in the long term. Consequently, numerous efforts are underway to address this unmet clinical need. The rarity of the disease limits the ability to conduct robust clinical trials, making in silico, ex vivo, and in vivo drug screenings essential for designing new therapeutic strategies for T-PLL. We conducted a drug repurposing analysis based on T-PLL gene expression data and identified proteasome inhibitors (PIs) as a promising new class of compounds capable of reversing the T-PLL phenotype. Treatment of ex vivo T-PLL cells with Bortezomib and Carfilzomib, two PI compounds, supported this hypothesis by demonstrating increased apoptosis in leukemic cells. The current lack of a suitable in vitro model for the study of T-PLL prompted us to perform similar experiments in the SUP-T11 cell line, validating its potential by showing an increased apoptotic rate. Taken together, these findings open new avenues for investigating the molecular mechanisms underlying the efficacy of PI in T-PLL and expand the spectrum of potential therapeutic strategies for this highly aggressive disease.

Competing Interests: Paolo Ghia received honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Janssen, Lilly/LoxoOncology, MSD, and Roche, and research funding from AbbVie, AstraZeneca, BMS, and Janssen, and is an Editor of HemaSphere. Marzia Varettoni received honoraria from AbbVie, AstraZeneca, BeiGene, and Janssen. The remaining authors declare no conflict of interest.

Background: Colorectal cancer is a worldwide leading cause of death accounting for high-rate mortality. Mutations in the epidermal growth factor receptor and RAS/MAPK pathways, as well as altered methylation genes profiles, have been described as molecular mechanisms promoting and sustaining tumour development and progression. Aberrant methylation is a well-known epigenetic mechanism involved in gene regulation; particularly several genes were reported as hypermethylated in CRC. Recently, it was shown that epigenetic alterations in genes such as neuropeptide y, proenkephalin and Wnt inhibitory factor 1 can be used as promising disease biomarkers. Almost all methods developed for the DNA methylation analysis combined next generation sequencing, conventional qRT-PCR or ddPCR with the prior DNA modification with sodium bisulfite., Methods and Results: We implemented a ddPCR method to assess the methylation status of Wnt inhibitory factor 1 and neuropeptide y using the methylation sensitive restriction enzyme approach that does not impact on DNA quality and guarantees the discrimination of DNA methylation independent of bisulfite conversion., Conclusions: We showed that this method is robust and sensitive also allowing the monitoring of CRC disease progression when applied to circulating free DNA samples from liquid biopsies, proving to be a fast and easy to implement assay to be used for the monitoring of the methylation pattern of clinically relevant target genes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Thomas Chatzikonstantinou received honoraria from AbbVie. Lydia Scarfò received honoraria from AbbVie, AstraZeneca, BeiGene, Lilly, Janssen, Octapharma. Gloria Iacoboni received honoraria and travel support from Novartis, Kite/Gilead, Bristol‐Myers Squibb, Abbvie, Autolus, Miltenyi, and AstraZeneca. Rosa Collado received support for attending meetings from Janssen‐Cilag and S.A. Sara Galimberti received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. Romain Guieze received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, and AstraZeneca. Eleftheria Hatzimichael received honoraria from AbbVie, Janssen‐Cilag, AstraZeneca, and Roche. Yair Herishanu received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. José‐Ángel Hernández‐Rivas received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. Ozren Jaksic received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. Kamel Laribi received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. Maya Koren‐Michowitz received honoraria from Novartis, Pfizer, and Gad Medical LTD. and support for attending meetings from Novartis. Arnon P. Kater received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, and Roche/Genentech, and support for attending meetings from Janssen and AbbVie. Ioannis Kotsianidis received honoraria and consulting fees from AbbVie and Janssen. Ivana Milosevic received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. Almudena Navarro‐Bailón received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. Jacopo Olivieri received honoraria from AbbVie, AstraZeneca, and Janssen. Gianluigi Reda received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. Gian M. Rigolin received honoraria for participation in speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. Mattia Schipani received honoraria and support for attending meetings from AstraZeneca, AbbVie, and Janssen‐Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. Tereza Shokralla and Stephan Stilgenbauer reports research funding from, consultancy or advisory role for, honoraria from, speakers' bureau participation for, and travel support from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Hoffmann‐La Roche, Incyte, Infinity, Janssen, Novartis, and Sunesis. Eric Tse received support for attending meetings from Takeda. Theodoros Vassilakopoulos received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier, and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. Candida Vitale received honoraria from AbbVie, consulting fees from AstraZeneca, and support for attending meetings from AstraZeneca, Takeda, and Janssen. Renata Walewska received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca, and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. Lucrecia Yañez received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. Francesc Bosch received consulting fees, honoraria, and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. Stephen Mulligan received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche, and BeiGene. Maria Angelopoulou received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. Fatih Demirkan received support for attending meetings from Janssen and AbbVie. Tomas Papajík received honoraria and advisory board fees from AbbVie, Janssen‐Cilag, and AstraZeneca, and support for attending meetings from AstraZeneca. Marta Coscia received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Constantine Tam received honoraria from AbbVie, Beigene, Janssen, and LOXO. Antonio Cuneo received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. Gianluca Gaidano received honoraria from Abbvie, AstraZeneca, BeiGene, Hikma, Incyte, Janssen, and Lilly. Niki Stavroyianni received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. Lukas Smolej received consulting fees, honoraria, and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. Martin Spacek received honoraria and consulting and advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Michael Doubek received research support and honoraria from AbbVie, AstraZeneca, and Janssen. Eugene Nikitin received honoraria from AbbVie. Kostas Stamatopoulos received research support from AbbVie, AstraZeneca, Janssen, Novartis, and Roche; honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Lilly, and Janssen. Paolo Ghia received research support from AbbVie, AstraZeneca, BMS, Janssen and honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Genmab, Janssen, Loxo Oncology @Lilly, MSD, Roche, and is an Editor of HemaSphere. Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Jana Kotaskova, Christos Demosthenous, Elisa Albi, Miguel Alcoceba, Salem Al‐Shemari, Thérèse Aurran‐Schleinitz, Francesca Bacchiarri, Sofia Chatzileontiadou, Zadie Davis, Marcos Daniel de Deus Santos, Maria Dimou, Elena Dmitrieva, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El‐Ashwah, Alicia Enrico, Andrzej Frygier, Andrea Galitzia, Eva Gimeno, Valerio Guarente, Sean Harrop, Elżbieta Kalicińska, Volkan Karakus, Bonnie Kho, Maria Kislova, Εliana Konstantinou, Zuzana Kubova, Jorge Labrador, Deepesh Lad, Luca Laurenti, Thomas Longval, Alberto Lopez‐Garcia, Juan Marquet, Stanislava Maslejova, Carlota Mayor‐Bastida, Biljana Mihaljevic, Fatima Miras, Riccardo Moia, Marta Morawska, Uttam K. Nath, Irina Panovska‐Stavridis, Maria Papaioannou, Cheyenne Pierie, Anna Puiggros, Rosa Ruchlemer, Annett Schiwitza, Yandong Shen, Tereza Shokralla, Martin Simkovic, Svetlana Smirnova, Dina S. A. Soliman, Tamar Tadmor, Kristina Tomic, Andrea Visentin, George Vrachiolias, Vojin Vukovic, Zhenshu Xu, Munci Yagci, Mohamed Yassin, Jana Zuchnicka, David Oscier, Alessandro Gozzetti, Panagiotis Panagiotidis, Blanca Espinet, Paolo Sportoletti, Gerassimos A. Pangalis, Viola M. Popov, Bella Biderman, Roberta Murru, Rainer Claus, Livio Trentin, Darko Antic, Olga B. Kalashnikova, Mark Catherwood, Sarka Pospisilova, and Anastasia Chatzidimitriou have no conflict of interest to disclose.

Introduction: The identification of baseline prognostic factors in Classical Hodgkin Lymphoma could help in tailoring a risk-based approach as the therapeutic landscape expands. Currently, the International Prognostic Score (IPS) represents the most used prediction tool in clinical practice, but other potential baseline risk predictors have been identified., Methods: We performed a retrospective analysis in a cohort of 274 patients treated with 18 FDG-PET/CT-guided ABVD to assess the prognostic significance of the IPS risk factors, and to validate the impact of the peripheral blood lymphocyte to monocyte (LMR) and neutrophil to lymphocyte (NLR) ratios on prognosis definition., Results: Among the considered risk factors, stage IV disease (HR 1.83), leukocytosis (HR 2.28), anemia (HR 3.23) and low LMR (HR 2.01) significantly predicted PFS, whereas male sex (HR 2.93), stage IV disease (HR 3.00) and lymphopenia (HR 7.84) significantly predicted OS. A 4 variable and a 3 variable prognostic system was subsequently proposed for PFS and OS, respectively. In both cases, a stark decrease in the survival probability was documented as the score increased. Moreover, by selecting only the significant IPS items and considering a more recently proposed prognostic factor (LMR) we were able to better identify patients at higher risk of relapsing after PET/CT-guided ABVD., Discussion: Although the IPS was still able to identify a subgroup of high-risk patients within our cohort of individuals treated with PET/CT-guided ABVD, not all the risk factors that it considers were found to have an impact on survival times. Moreover, by selecting only the significant IPS items and considering a more recently proposed prognostic factor (LMR) we were able to better identify patients at higher risk of relapse, in an effort to contribute to the building of a modern risk prediction tool that can help guide treatment choices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Cellini, Cavarretta, Angotzi, Ruocco, Serafin, Danesin, Pizzi, Gregianin, Vio, Crimì, Vianello, Piazza, Trentin and Visentin.)

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase mainly found in the focal adhesion regions of the plasma membrane and it has a crucial role in migration and the remodeling of cellular morphology. FAK is also linked to several aspects of cancer biology, from cytokine production to angiogenesis, drug resistance, invasion, and metastasis, as well as epithelial-to-mesenchymal transition. The gene locus of FAK is frequently amplified in several human tumors, thus causing FAK overexpression in several cancers. Furthermore, FAK can influence extracellular matrix production and exosome secretion through cancer-associated fibroblasts, thus it has an important role in tumor microenvironment regulation. Although the role of FAK in solid tumors is well known, its importance in onco-hematological diseases remains poorly explored. This review collects studies related to FAK significance in onco-hematological diseases and their microenvironments. Overall, the importance of FAK in blood tumors is increasingly evident, but further research is required to confirm it as a new therapeutic target in hematological contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Capasso, Mouawad, Castronuovo, Ruggeri, Visentin, Trentin and Frezzato.)

The prognostic and predictive role of specific gene mutations in Waldenström Macroglobulinemia (WM) is well-ascertained whereas the clinical impact of chromosome aberrations is far less known. Recent work has provided initial evidence for an adverse prognostic impact of some aberrations, such as del(6q), while other studies suggest a possible relationship between some clinical features (e.g. advanced age and/or inflammatory status) and specific cytogenetic abnormalities. To add to the still limited knowledge on WM cytogenetics and its clinical implications, we herein report our experience in a cohort of WM patients across 23 years. Based on our retrospective study, we found that abnormal karyotype was more represented in older patients and maintained a statistically significant independence from other molecular, clinical, and biological features related to WM. The presence and number of cytogenetic aberrations correlated with inferior overall and progression-free survival outcomes regardless of the type of single chromosome aberration. Our data suggests that the role of the altered karyotype deserves to be further clarified especially in elderly WM patients, in whom cytogenetic abnormalities and disease biology appear to be characterized by a higher degree of complexity., (© 2024. The Author(s).)