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Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

ABSTRACT Objectives Methods Results Conclusions The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP‐CML patients.A retrospective analysis was conducted on 332 CP‐CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the “Campus CML” project.Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second‐generation TKIs (2G‐TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G‐TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra‐hematologic toxicity (9.5%), with no significant difference between IM and 2G‐TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G‐TKIs.IM was in our Centers the preferred frontline therapy for older CP‐CML patients, with increasing utilization after the introduction of generic formulations. However, 2G‐TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population. [ABSTRACT FROM AUTHOR]

Background: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2-high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate-1 (INT1) patients, with scarce information on responses and outcome., Methods: The authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX-MF" retrospective study., Results: At baseline (BL), 595 (56.2%) patients were at INT1-risk according to DIPSS (PMF) or MYSEC-PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High-molecular-risk (HMR) mutations (IDH1/2, ASXL-1, SRSF2, EZH2, U2AF1 Q157 ) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 10 9 /L: n = 43; white blood cells <4 x 10 9 /L: n = 40). After 6 months on RUX, IWG-MRT-defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12-3.76]; p = .01)., Conclusions: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high-risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less-responsive INT1 patients, who may benefit for alternative therapeutic strategies., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Chronic Myeloid Leukemia (CML) is marked by the BCR::ABL1 fusion gene. Monitoring tyrosine kinase inhibitor (TKI) therapy response is crucial for treatment management, thus, limitations in Reverse Transcription quantitative PCR's (RT-qPCR) accuracy and sensitivity led to the exploration of alternative methods like digital PCR (dPCR). This study evaluated dPCR efficacy in detecting Minimal Residual Disease (MRD) in CML patients undergoing TKI therapy. 79 CML patients were enrolled (NP 3809 clinical trial), with samples analysed using both methods. The achievement and stability of Deep Molecular Response (DMR) were assessed over a 2-year period following the first DMR achievement. A comparative statistical analysis of MRD and DMR attainment, stability, and potential TFR achievement using both RT-qPCR and dPCR was conducted, supported by chi-squared tests, Fisher's exact tests, and Kaplan-Meier analysis. In 69/79 patients, dPCR either anticipated or coincided DMR achievement as compared to RT-qPCR. Among them, 52/69 achieved a stable DMR according to RT-qPCR, while 44/69 according to dPCR. Thus, dPCR capability to anticipate or coincide the achievement of a stable DMR resulted with p = 0.0012 and p = 0.0017, respectively. Transcript type and TKI choice did not influence DMR achievement or stability by either method. These findings highlight dPCR as a sensitive and accurate tool for monitoring MRD in CML patients, providing information for treatment management decisions, and potentially enhancing the selection of candidates for treatment-free remission. Further standardization of dPCR methodologies is warranted to leverage their benefits in clinical practice., Competing Interests: Declarations. Ethics approval: The protocol was approved by the ethical committee of Verona, Milano, Udine, Brescia and Padua in July 2019. Patient consent: The studies were conducted in accordance with the Declaration of Helsinki and the enrolled patients gave their written informed consent. Competing interests: The authors declare no competing interests. Clinical trial registration: NP 3809 clinical trial., (© 2024. The Author(s).)

Background: In the last decade, TKIs improved the overall survival (OS) of chronic myeloid leukemia (CML) patients who achieved a deep and sustained molecular response (DMR, defined as stable MR4 and MR4.5). Those patients may attempt therapy discontinuation. In our analysis, we report the differences in eligibility criteria due to time of response and different TKI used as frontline treatment analyzed in a large cohort of CP-CML patients., Methods: Data were exported by LabNet CML, a network founded by GIMEMA in 2014. The network standardized and harmonized the molecular methodology among 51 laboratories distributed all over Italy for the diagnosis and molecular residual disease (MRD) monitoring., Results: Out of 1777 patients analyzed, 774 had all evaluable timepoints (3, 6, and 12 months). At 3 months, 40 patients obtained ≥MR4: of them 14 (3.6%) with imatinib, 8 (5.8%) with dasatinib, and 18 (7.4%) with nilotinib (P = .093); at 6 months, 146 patients were in MR4: 42 (11%) with imatinib, 38 (28%) with dasatinib, and 66 (27%) with nilotinib (P < .001). At 12 months, 231 patients achieved a DMR: 85 (22%) with imatinib, 55 (40%) with dasatinib and 91 (38%) with nilotinib (P < .001). Achieving at least ≥MR2 at 3 months, was predictive of a DMR at any timepoint of observation: with imatinib 67% versus 30% of patients with 2 years was significant for patients who at 3 months had ≥MR2 (18% vs. 9.9% of pts with

Background Rosacea is a chronic inflammatory disease of the skin characterised by facial erythema, oedema, telangiectasias, papules, pustules and nodules. There is a paucity of effective therapeutic modalities for the management of rosacea. Intense Pulsed Light (IPL), a modality in which flash lamps installed in an optical treatment device (head or tip) with mirrors to reflect light, has in recent times gained popularity in the management of this condition. Aim This systematic review aims to evaluate the efficacy, safety and adverse effects of IPL treatment for rosacea. Methods This systematic review was conducted in accordance with the Preferred Reporting Item for Systematic Reviews and Meta-Analysis. The electronic databases searched were Medline, PubMed and Scopus databases. The Risk of bias in non-randomised studies of interventions (ROBINS-I) and risk-of-bias tools for randomised trials (RoB-2) was employed to assess the risk of bias. Results Of a total of 233 articles retrieved from Medline, Scopus and PubMed databases, 14 studies qualified for final analysis. The studies included patients with Fitzpatrick skin types I to IV, with ages ranging from 15 to 78 years. Although the included studies showed heterogeneity between the parameters used, most studies demonstrated positive effects of IPL treatment on telangiectasia and erythema in rosacea and that the adverse effects presented were transitory. Limitation The methodological quality of the included studies was poor. Conclusion Although most studies showed the efficacy of IPL in the treatment of rosacea, the poor quality of the studies was of concern.

Background: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking., Objective: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment., Methods: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points)., Results: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %., Conclusions: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies., Competing Interests: Declaration of competing interest All the authors have approved this manuscript and declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Abstract: Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308μg/L vs 146μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Intermittent treatment with tyrosine kinase inhibitors (TKIs) is an option for elderly chronic myeloid leukemia (CML) patients who are often candidates for life-long treatment., Materials and Methods: The Italian phase III multicentric randomized Optimize TKIs Multiple Approaches (OPTkIMA) study aimed to evaluate if a progressive de-escalation of TKIs is able to maintain the molecular remission (MR) 3.0 and to improve Health-Related Quality of Life (HRQoL) in CML elderly patients., Results: A total of 215 patients in stable MR 3.0 /MR 4.0 were randomized to receive an intermittent TKI schedule 1 month ON-1 month OFF for 3 years (FIXED arm; n = 111) vs. a progressive de-escalation TKI dose up to one-third of the starting dose at the 3rd year (PROGRESSIVE arm; n = 104). Two hundred three patients completed the 3rd year of OPTkIMA study. At the last follow-up, MR 3.0 loss was 27% vs. 46% (P = .005) in the FIXED vs PROGRESSIVE arm, respectively. None of these patients experienced disease progression. The 3-year probability of maintaining the MR 3.0 was 59% vs. 53%, respectively (P = .13). HRQoL globally improved from the baseline to the 3rd year, without any significant difference between the 2 arms. After the 3rd year, the proportion of patients who was address to TKI discontinuation in the 2 arms was 36% (FIXED) vs. 58% (PROGRESSIVE) (P = .03)., Conclusions: The intensification of intermittent TKI therapy is associated with a higher incidence of MR 3.0 loss, but those patients who maintain the MR 3.0 molecular response at the end of the study have been frequently considered eligible for TFR. The HRQoL generally improved during the de-escalation therapy in both randomization arms., Competing Interests: Disclosures AI: Speaker honoraria – AOP, BMS, GSK, Incyte, Novartis and Pfizer. CB: Speaker's Bureau – Novartis, Incyte and Pfizer AB: Advisory Board and Consultancy - Novartis, Incyte, BMS, Pfizer. GR: Speaker's Bureau and Advisory Boards - Incyte, Novartis and Pfizer. MT: Speaker's Bureau – Novartis, Incyte and BMS. AMR: research funding - AstraZeneca, European Hematology Association, Transcan2-ERANET and Italian Association for Cancer Research (Fondazione AIRC); honoraria - Amgen, Celgene, Janssen and Takeda. All the other Authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Anemia is frequently present in patients with myelofibrosis (MF), and it may be exacerbated by treatment with the JAK2-inhibitor ruxolitinib (RUX). Recently, a relevant blast phase (BP) incidence has been reported in anemic MF patients unexposed to RUX., Methods: The authors investigated the incidence of BP in 886 RUX-treated MF patients, included in the "RUX-MF" retrospective study., Results: The BP incidence rate ratio (IRR) was 3.74 per 100 patient-years (3.74 %p-y). At therapy start, Common Terminology Criteria for Adverse Events grade 3-4 anemia (hemoglobin [Hb] <8 g/dL) and severe sex/severity-adjusted anemia (Hb <8/<9 g/dL in women/men) were present in 22.5% and 25% patients, respectively. IRR of BP was 2.34 in patients with no baseline anemia and reached respectively 4.22, 4.89, and 4.93 %p-y in patients with grade 1, 2, and 3-4 anemia. Considering the sex/severity-adjusted Hb thresholds, IRR of BP was 2.85, 4.97, and 4.89 %p-y in patients with mild/no anemia, moderate, and severe anemia. Transfusion-dependent patients had the highest IRR (5.03 %p-y). Progression-free survival at 5 years was 70%, 52%, 43%, and 27% in patients with no, grade 1, 2, and 3-4 anemia, respectively (p < .001). At 6 months, 260 of 289 patients with no baseline anemia were receiving ruxolitinib, and 9.2% had developed a grade 3-4 anemia. By 6-month landmark analysis, BP-free survival was significantly worse in patients acquiring grade 3-4 anemia (69.3% vs. 88.1% at 5 years, p < .001)., Conclusions: This study highlights that anemia correlates with an increased risk of evolution into BP, both when present at baseline and when acquired during RUX monotherapy. Innovative anemia therapies and disease-modifying agents are warranted in these patients., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Introduction: The introduction of the first JAK inhibitor (JAKi) ruxolitinib 10 years ago represented a pivotal advancement in myelofibrosis (MF) treatment, mostly in terms of spleen and symptoms response. Nowadays three more JAKi, fedratinib, pacritinib, and momelotinib, are available for both ruxolitinib-resistant and naïve patients. Moreover, many drugs are currently being investigated, both alone and in combination with JAKi., Areas Covered: In this review we discuss the long-term data of ruxolitinib and more recent evidence coming from clinical trials of fedratinib, pacritinib, and momelotinib, used as first- or second-line MF therapy. More, focus is set on data from non-JAKi drugs, such as the quite extensively studied BET-inhibitors (pelabresib) and BCL-inhibitors (navitoclax), novel target therapies, and drugs aimed to improve anemia, still representing a major determinant of reduced survival in MF., Expert Opinion: It's now evident that JAKi monotherapy, though clinically effective, is rarely able to change MF natural history; novel drugs are promising but long-term data are inevitably lacking. We feel that soon MF treatment will require clinicians to select the most appropriate JAKi inhibitor, based on patient characteristics, associating either front-line or in case of early suboptimal response, non-JAKi drugs with the aim to pursue disease modification.

The present study aims to characterize and to evaluate the biological effects of a skin dressing manufactured with the organic part of the Chondrilla caribensis marine sponge (called spongin-like collagen (SC)) associated or not to photobiomodulation (PBM) on the skin wound healing of rats. Skin dressings were manufactured with SC and it was characterized using scanning electron microscopy (SEM) and a tensile assay. In order to evaluate its biological effects, an experimental model of cutaneous wounds was surgically performed. Eighteen rats were randomly distributed into three experimental groups: control group (CG): animals with skin wounds but without any treatment; marine collagen dressing group (DG): animals with skin wounds treated with marine collagen dressing; and the marine collagen dressing + PBM group (DPG): animals with skin wounds treated with marine collagen dressing and PBM. Histopathological, histomorphometric, and immunohistochemical evaluations (qualitative and semiquantitative) of COX2, TGFβ, FGF, and VEGF were done. SEM demonstrates that the marine collagen dressing presented pores and interconnected fibers and adequate mechanical strength. Furthermore, in the microscopic analysis, an incomplete reepithelialization and the presence of granulation tissue with inflammatory infiltrate were observed in all experimental groups. In addition, foreign body was identified in the DG and DPG. COX2, TGFβ, FGF, and VEGF immunostaining was observed predominantly in the wound area of all experimental groups, with a statistically significant difference for FGF immunostaining score of DPG in relation to CG. The marine collagen dressing presented adequate physical characteristics and its association with PBM presented favorable biological effects to the skin repair process., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for adult Philadelphia-positive ALL (Ph+ ALL), which enrolled 63 patients of all ages. At a median follow-up of 53 months, disease-free survival, overall survival, and event-free survival are 75.8%, 80.7%, and 74.6%, respectively. No events have occurred among early molecular responders. A significantly worse outcome was recorded for IKZF1 plus patients. Twenty-nine patients-93.1% being in molecular response (ie, complete molecular response or positive nonquantifiable) after dasatinib/blinatumomab-never received chemotherapy/transplant and continued with a tyrosine kinase inhibitor only; 28 patients remain in long-term complete hematologic response (CHR). An allogeneic transplant was carried out in first CHR mainly in patients with persistent minimal residual disease; 83.3% of patients are in continuous CHR. The transplant-related mortality was 12.5% for patients transplanted in first CHR and 13.7% overall. Nine relapses and six deaths have occurred. ABL1 mutations were found in seven cases. The final analysis of the D-ALBA study shows that a chemotherapy-free induction/consolidation regimen on the basis of a targeted strategy (dasatinib) and immunotherapy (blinatumomab) is effective in inducing durable long-term hematologic and molecular responses in adult Ph+ ALL, paving the way for a new era in the management of these patients.

Patients with chronic myeloid leukemia (CML) treated with nilotinib or ponatinib may experience arterial occlusive events (AOEs). It is currently recommended to thoroughly assess cardiovascular risk factors before treating CML. We identified 455 consecutive CML adult patients, 335 treated with nilotinib and 120 with ponatinib; 380 patients without previous cardiovascular diseases or diabetes were stratified according to the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Older Persons (SCORE2-OP). This updated algorithm from the European Society of Cardiology (ESC) estimates a 10-year risk of fatal and non-fatal cardiovascular diseases. It is based on sex, age, smoking habits, systolic blood pressure, non-high-density lipoprotein cholesterol, and European geographical region of cardiovascular risk. The SCORE2/SCORE2-OP algorithm translated more patients (50.2%) to the high-very high cardiovascular risk category than the previous SCORE (25.3%). Patients with a high to very high SCORE2/SCORE2-OP risk showed a significantly higher incidence rate of AOEs (69.2% vs. 46.5%, p < 0.001). The older SCORE was less specific in estimating AOEs in patients classified as low-intermediate risk (69.8 vs. 54.2%). In multivariate analysis, no associations were found between AOEs and gender, age, and type or dose of tyrosine kinase inhibitor. Only the SCORE2/SCORE2-OP risk was confirmed as a significant predictive factor (p = 0.028; hazard ratio = 2.2; 95% confidence interval = 1.1-4.5). Patients with AOEs required, in most cases, imaging diagnostic tests, additional drugs, and sometimes invasive procedures, increasing access to visits and hospital management. This real-life study suggested that the SCORE2 and SCORE2-OP charts could help identify cardiovascular fragility in CML patients providing them with more attention and a proper TKI selection., (© 2023. The Author(s).)

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Chitosan (CS) is a polycationic polysaccharide comprising glucosamine and N-acetylglucosamine and constitutes a potential material for use in cartilage tissue engineering. Moreover, CS hydrogels are able to promote the expression of cartilage matrix components and reduce inflammatory and catabolic mediator production by chondrocytes. Although all the positive outcomes, no review has analyzed the effects of CS hydrogels on cartilage repair in animal models., Methods: This study aimed to review the literature to examine the effects of CS hydrogels on cartilage repair in experimental animal models. The search was done by the descriptors of the Medical Subject Headings (MeSH) defined below: "Chitosan," "hydrogel," "cartilage repair," and "in vivo." A total of 420 articles were retrieved from the databases Pubmed, Scopus, Embase, Lilacs, and Web of Science. After the eligibility analyses, this review reported 9 different papers from the beginning of 2002 through the middle of 2022., Results: It was found that cartilage repair was improved with the treatment of CS hydrogel, especially the one enriched with cells. In addition, CS hydrogel produced an upregulation of genes and proteins that act in the cartilage repair process, improving the biomechanical properties of gait.., Conclusion: In conclusion, CS hydrogels were able to stimulate tissue ingrowth and accelerate the process of cartilage repair in animal studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The authors assessed the clinical utility of patient-reported symptom monitoring in the setting of newly diagnosed chronic myeloid leukemia (CML). The primary objective was to evaluate adherence to therapy., Methods: The authors conducted an international prospective study that included patients with newly diagnosed, chronic-phase CML. Before clinical consultation, patients were provided a tablet computer to self-rate their symptoms, and the results were available in real time to each physician during the patient's visit. Adherence was assessed by pill count and with a validated self-reported questionnaire. The proportions of optimal responders at 3 and 6 months were assessed according to the European LeukemiaNet criteria., Results: Between July 2020 and August 2021, 94 patients with a median age of 57 years were enrolled. Pill count adherence analysis indicated that 86 of 93 evaluable patients (92.5%) took at least 90% of prescribed tyrosine kinase inhibitor therapy during the 6-month observation period. The online platform was well accepted by patients and physicians. An optimal response was achieved by 69 of 79 patients (87.3%) at 3 months and by 61 of 81 patients (75.3%) at 6 months., Conclusions: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates (ClinicalTrials.gov identifier NCT04384848)., (© 2023 American Cancer Society.)