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Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal expansion within the bone marrow (BM) and remains largely incurable despite recent therapeutic advances. While prognostic indicators have predominantly focused on tumor-intrinsic features, the BM tumor microenvironment (TME) plays a critical role in disease progression and therapeutic resistance. Here, we present a robust prognostic model derived from transcriptomic profiling of the CD138-negative BM fraction, enabling precise risk stratification of patients undergoing bortezomib-based induction therapy. Using bioinformatic deconvolution and a custom immune-stromal signature matrix, we identified gene expression patterns representative of the MM TME. Through rigorous feature selection and elastic-net penalized Cox regression, we developed the MM-5C model, consisting of five genes ( SOX11 , METTL11B , C3 , RBM10 , and HOMEZ ), which stratifies patients into biologically distinct risk groups and demonstrates prognostic independence from established cytogenetic and clinical staging systems. This model underscores the pivotal role of TME components in shaping therapeutic outcomes and offers a scalable, clinically translatable tool for personalized risk stratification. Our findings highlight the necessity of integrating microenvironmental insights into MM prognostication and pave the way for microenvironment-informed therapeutic decision-making.

Background: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1–3 prior treatments. Methods: Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance. Results: After a median follow-up time of 12.9 months (range, 1–77), the overall response rate, at least a very good partial response rate, and median progression-free survival time were 79.3%, 56.1%, and 24.4 months, respectively. This slightly lower performance compared to that in the IKEMA study may be attributed to the well-known poor prognostic impact of lenalidomide refractoriness (len-R), developed by all our patients during maintenance therapy, and to a higher proportion of patients with extramedullary disease present in our series, which was identified as the only factor significantly affecting the PFS in multivariable analysis. The median overall survival was not reached, as in the pivotal trial, while the 1-year survival probability was 85.1%. Regarding the safety profile, our findings were consistent with those of the IKEMA trial, with no new safety signals reported. Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and lenalidomide maintenance.

The unstructured nature of Real-World (RW) data from onco-hematological patients and the scarce accessibility to integrated systems restrain the use of RW information for research purposes. Natural Language Processing (NLP) might help in transposing unstructured reports into standardized electronic health records. We exploited NLP to develop an automated tool, named ARGO (Automatic Record Generator for Onco-hematology) to recognize information from pathology reports and populate electronic case report forms (eCRFs) pre-implemented by REDCap. ARGO was applied to hemo-lymphopathology reports of diffuse large B-cell, follicular, and mantle cell lymphomas, and assessed for accuracy (A), precision (P), recall (R) and F1-score (F) on internal (n = 239) and external (n = 93) report series. 326 (98.2%) reports were converted into corresponding eCRFs. Overall, ARGO showed high performance in capturing (1) identification report number (all metrics > 90%), (2) biopsy date (all metrics > 90% in both series), (3) specimen type (86.6% and 91.4% of A, 98.5% and 100.0% of P, 92.5% and 95.5% of F, and 87.2% and 91.4% of R for internal and external series, respectively), (4) diagnosis (100% of P with A, R and F of 90% in both series). We developed and validated a generalizable tool that generates structured eCRFs from real-life pathology reports.

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Autologous stem cell transplantation (ASCT), doubled in selected cases, followed by lenalidomide maintenance (LM) remains the standard treatment after induction therapy for newly diagnosed, transplant eligible patients with multiple myeloma (TEMM). Notwithstanding, evidences about how these approaches have been applied and how they have performed in the real-life setting, before the introduction of daratumumab within the induction regimens, are quite limited. Herein, we report the outcome of 300 MM patients, who underwent single (45%) or double (55%) ASCT, and received (42%) or not (58%) lenalidomide maintenance, outside of clinical trials, between December 2001 and February 2020, within the “Rete Ematologica Pugliese”. After a median follow-up of 65 months (range: 9-186), median PFS was significantly longer in patients who underwent double ASCT compared to those who received single ASCT (66 vs. 53 months, respectively, p  = 0.01). Likewise, after a median follow-up of 62 months (range: 9-174), patients who received LM had a significantly better PFS respect to those who did not (72 vs. 36 months, respectively p  < 0.001). Concerning OS, it was not influenced by single or double ASCT (although a trend favoring double ASCT was observed), while LM significantly improved OS (142 vs. 108 months, p  = 0.01). At multivariable analysis factors influencing PFS were achievement of complete remission after first ASCT, double ASCT and LM, while those impacting on OS were high risk cytogenetics, LDH and LM. In the context of a rapidly changing therapeutic scenario, our data might contribute to a real-life, historical benchmark for current and future treatments of TEMM patients.

Erythropoietin (Epo) is the crucial cytokine regulator of red blood cell production, and recombinant human erythropoietin (rHuEpo) is widely used in clinical practice for the treatment of anemia, primarily in kidney disease and in cancer. Increasing evidence suggests several biological roles for Epo and its receptor, Epo-R, unrelated to erythropoiesis, including angiogenesis. Epo-R has been found expressed in various non-haematopoietic cells and tissues, and in cancer cells. Here, we detected the expression of Epo-R in bone marrow-derived macrophages (BMMAs) from multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) patients and assessed whether Epo/Epo-R axis plays a role in MM macrophage-mediated angiogenesis. We found that Epo-R is over-expressed in BMMAs from MM patients with active disease compared to MGUS patients. The treatment of BMMAs with rHuEpo significantly increased the expression and secretion of key pro-angiogenic mediators, such as vascular endothelial growth factor, hepatocyte growth factor and monocyte chemotactic protein (MCP-1/CCL-2), through activation of JAK2/STAT5 and PI3 K/Akt pathways. In addition, the conditioned media harvested from rHuEpo-treated BMMAs enhanced bone marrow-derived endothelial cell migration and capillary morphogenesis in vitro, and induced angiogenesis in the chorioallantoic membrane of chick embryos in vivo. Furthermore, we found an increase in the circulating levels of several pro-angiogenic cytokines in serum of MM patients with anemia under treatment with Epo. Our findings highlight the direct effect of rHuEpo on macrophage-mediated production of pro-angiogenic factors, suggesting that Epo/Epo-R pathway may be involved in the regulation of angiogenic response occurring in MM.

Primary renal lymphoma (PRL) is a rare form of non-Hodgkin’s lymphoma (NHL) restricted to and primarily involving one or both kidneys, with no lymph node extension. It accounts for <1% of extranodal lymphomas, and descriptions in the literature are limited. Here, we describe an unprecedented case of bilateral PRL in a 44-year-old woman with Turner syndrome and discuss both diagnostic and therapeutic issues in the light of the available literature in the field. A personalized approach to this rare disease is necessary.

Intracerebral hemorrhages (ICH) during implantation of stereo‐EEG electrodes are rare. The impact of tobacco‐free nicotine consumption on periprocedural bleeding is uncertain. We present a 20+ year‐old man with drug‐resistant epilepsy who underwent stereo‐EEG with 17 depth electrodes. Within a few days after insertion, the patient developed multiple ICHs in the electrode trajectories and an intradural hemorrhage after a diagnostic spinal tap. We performed the investigation of the clotting system and whole‐exome sequencing (WES). WES identified a heterozygous mutation c.4698G>T, p.(Trp1566Cys) in COL4A2 (NM_001846.4) encoding a collagen type‐IV alpha‐2 chain inherited from his seemingly healthy mother. As COL4A2 mutations had been identified in four adult patients with ICH we postulated that the identified variant presents a potential risk factor. Notably, mutations encoding other collagens have been linked to cerebral hemorrhages (COL4A1) and increased propensity to trigger ICH upon smoking (COL1A2). Our patient consumed at least 24 oral nicotine pouches (containing 11 mg nicotine each) per day. We consider the patient's COL4A2 mutation in combination with his substantial nicotine consumption as likely predisposition to multiple ICHs precipitated by stereo‐EEG. Patients with nicotine consumption and any collagen mutation may have a substantially higher risk for hemorrhagic complications in SEEG and other neurosurgical procedures. Plain Language Summary A young man with drug‐resistant epilepsy experienced multiple intracerebral hemorrhages after implantation of SEEG electrodes for presurgical evaluation and concomitantly a intradural hemorrhage after a lumbar spinal tap. A collagen IV mutation of unclear significance and heavy use of oral nicotine pouches were the only potential risk factors identified. As collagen mutations were previously described risk factors and smoking in particular worsens the bleeding risk in collagen mutations, further research is warranted to prevent hemorrhages in neurosurgical procedures. Nicotine consumption in any form is a preventable risk factor.

Nanostructured Pb electrodes consisting of nanowire arrays were obtained by electrodeposition, to be used as negative electrodes for lead–acid batteries. Reduced graphene oxide was added to improve their performances. This was achieved via the electrochemical reduction of graphene oxide directly on the surface of nanowire arrays. The electrodes with and without reduced graphene oxide were tested in a 5 M sulfuric acid solution using a commercial pasted positive plate and an absorbed glass mat separator in a zero-gap configuration. The electrodes were tested in deep cycling conditions with a very low cut-off potential. Charge–discharge tests were performed at 5C. The electrode with reduced graphene oxide outperformed the electrode without reduced graphene oxide, as it was able to work with a very high utilization of active mass and efficiency. A specific capacity of 258 mAhg−1–very close to the theoretical one–was achieved, and the electrode lasted for more than 1000 cycles. On the other hand, the electrode without reduced graphene oxide achieved a capacity close to 230 mAhg−1, which corresponds to a 90% of utilization of active mass.

Robotic surgery with Da Vinci has revolutionized the treatment of several diseases, including prostate cancer; nevertheless, costs remain the major drawback. Recently, new robotic platforms entered the market aiming to reduce costs and improve the access to robotic surgery. The aim of the study is to compare direct cost for initial hospital stay of radical prostatectomy performed with two different robotic systems, the Da Vinci and the new Hugo RAS system. This is a projection study that applies cost of robotic surgery, derived from a local tender, to the clinical course of robotic radical prostatectomy (RALP) performed with Da Vinci and Hugo RAS. The study was performed in a public referral center for robotic surgery equipped with both systems. The cost of robotic surgery from a local tender were considered and included rent, annual maintenance, and a per-procedure fee covering the setup of four robotic instruments. Those costs were applied to patients who underwent RALP with both systems since November 2022. The primary endpoint is to evaluate direct costs of initial hospital stay for Da Vinci and Hugo RAS, by considering equipment costs (as derived from the tender), and costs of theater and of hospitalization. The direct per-procedure cost is €2,246.31 for a Da Vinci procedure and €1995 for a Hugo RALP. In the local setting, Hugo RAS provides 11% of cost saving for RALP. By applying this per-procedure cost to our clinical data, the expenditure for the entire index hospitalization is € 6.7755,1 for Da Vinci and € 6.637,15 for Hugo RALP. The new Hugo RAS system is willing to reduce direct expenditures of robotic surgery for RALP; furthermore, it provides similar peri-operative outcomes compared to the Da Vinci. However, other drivers of costs should be taken into account, such as the duration of OR use—that is more than just console time and may depend on the facility’s background and organization. Further variations in direct costs of robotic systems are related to caseload, local agreements and negotiations. Thus, cost comparison of new robotic platform still remains an ongoing issue.