Search

The detection of pre-invasive tumors prior to the appearance of advanced clinical symptoms will enhance the effect of medical intervention at the earliest stage and reduce premature cancer deaths. Tumor biomarkers detection represents a powerful alternative to taking invasive biopsies; hence, biosensing technology is emphasized. Cancer diagnostics have evolved from the macroscopic detection of malignant tumors to the facile assessment of tumor biomarkers using miniaturized detection devices, such as immunosensors. Innovative immunosensors have become the most eminent candidate for analyzing oncomarkers to meet the requirements of medical diagnostics. Hence the development of highly selective immunosensors for the sensitive detection of oncomarker paves new directions for personal and medical supervision. Graphene and its derivatives are emerging carbon materials employed in developing sensors, in view of their exceptional physicochemical properties that amplify the device's sensitivity. Therefore, this review was designed to present a comprehensive interpretation of the recently developed graphene-based electrochemical immunosensors for detecting broad-spectrum oncomarker carcinoembryonic antigen (CEA). The article highlights the recent advances in signal amplification strategies accomplished utilizing graphene and its nanomaterials (2017 to mid-2022). Different electroanalytical techniques employed for CEA sensing have been discussed, and the sensor's performances are substantiated. The readers are also provided with significant statistical information on the reported immunosensors and their performance comparison: a technique used, working range, detection limit, real sample recoveries, reproducibility, and stability. Finally, the review concludes with the associated challenges and outlines the approach required to realize their successful translation into clinical settings.

The utilization of bio-functionalities such as biorecognition or catalysis derived them their name biosensors. Bio-electrochemical sensing is a new discipline that combines the advantages of biological detection and electrochemical transduction. Bio-electrochemical sensors are devices that use biological materials such as enzymes, antibodies, DNA, or cells as receptors to detect target analytes in a variety of samples. Electrodes convert biological interactions into electrical impulses, which can be studied using various electrochemical techniques. Bio-electrochemical sensors have demonstrated significant promise for use in clinical diagnostics, environmental monitoring, food safety, and biotechnology. Biosensors have received numerous applications in recent years because they are fast, simple, and inexpensive for practical applications. In this article, we cover the basic principles, design strategies, immobilization and regeneration techniques, along with the advantages and applications of bio-electrochemical sensors. Finally, this article discusses the rationale for developing electrochemical biosensors in the context of the various bio-receptors that can be applied.

Introduction: Ropeginterferon alfa-2b-njft (ropeg) was approved and recommended as a preferred cytoreductive treatment for polycythemia vera (PV). The approved regimen requires an initial dose of 100 μg or 50 μg if transitioning from hydroxyurea (HU) and up-titrations of 50 μg every two weeks to 500 μg maximumly. The time to achieve the plateau dose takes approximately 20 weeks. This study compares the approved regimen with a higher initial dose and accelerated dose titration (HIDAT) regimen. Methods and Conclusion: ECLIPSE-PV is a randomized, open-label, multicenter trial in patients with PV in the US and Canada. Patients received ropeg either per the approved dosing schema, or HIDAT regimen, i.e., 250 μg on Day 0, 350 μg at Week 2, and 500 μg from Week 4 thereafter if tolerable. The primary endpoint is complete hematologic response (CHR) rate at Week 24. CHR is defined as hematocrit <45%, white blood cells <10×109/L, platelets ≤400×109/L without phlebotomy in the previous 12 weeks. Secondary endpoints include molecular response, safety and tolerability, and quality of life. A total of 111 patients were randomized and the last patient was enrolled on June 21, 2024. As of November 12, 2024, the discontinuation rate was 14.4% and 16 patients (14.4%) completed the study. The study is expected to be completed in the summer of 2025. This is the first prospective trial comparing two dosing regimens of ropeg. The results will inform the optimal treatment strategy for patients with PV., (S. Karger AG, Basel.)

This study contributes to the circular economy (CE) literature by empirically testing the influence of CE capabilities on the adoption of CE practices, a relationship that has largely been explored conceptually. It also investigates whether institutional aspects mediate this effect and examines how the adoption of CE practices impacts business performance and organizational resilience. Employing a mixed-methods approach, the research integrates survey data analyzed using generalized structured component analysis (GSCA) and qualitative insights from structured interviews with firms operating in Brazil-an emerging market characterized by an "institutional vacuum" due to outdated regulations and a lack of government incentives for CE practices. The findings demonstrate that CE capabilities positively affect the adoption of CE practices, which, in turn, enhance both business performance and organizational resilience. However, institutional aspects do not mediate this relationship, highlighting firms' ability to pursue CE practices despite regulatory voids. This originality lies in uncovering how CE practices thrive in contexts of limited policy support, emphasizing mimetic pressures and competitive advantage as driving factors. The study provides actionable insights for policymakers to address regulatory barriers and create supportive frameworks for CE adoption. Practitioners are encouraged to leverage CE practices as strategic tools for resilience and competitiveness in challenging institutional environments., Competing Interests: Declaration of competing interest The authors 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 © 2025 Elsevier Ltd. All rights reserved.)

Selinexor is an investigational, selective oral XPO1 inhibitor that may inhibit myelofibrosis (MF)-relevant JAK/STAT and non-JAK/STAT pathways with potential synergy with ruxolitinib. SENTRY (XPORT-MF-034; NCT04562389) is a Phase 1/3 study evaluating safety and efficacy of selinexor plus ruxolitinib for treatment of patients with JAK inhibitor (JAKi) treatment-naïve MF. The Phase 1 open label portion of the study included a 3 + 3 dose escalation and dose expansion, with no dose limiting toxicities observed. Described here is the Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate selinexor+ruxolitinib versus placebo+ruxolitinib in patients with JAKi treatment-naïve MF. Approximately 350 patients will be enrolled. Primary endpoints will evaluate spleen volume reduction ≥ 35% and absolute mean change in total symptom score from baseline to week 24. Clinical Trial Registration: NCT04562389 (ClinicalTrials.Gov).

Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 10 9 /L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 10 9 /L in the PERSIST-2 study. Patients on study at the start of the 12-week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non-responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non-responders (HR, 0.00; 95% CI, 0.00-0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 10 9 /L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Importance: Polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons., Observations: Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common. Patients may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort. More than 95% of patients have a JAK2 gene variant, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea. Among 7 cohorts (1545 individuals), the median survival from diagnosis was 14.1 to 27.6 years. Prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events, which could involve unusual sites, such as splanchnic veins. PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis (platelet count, ≥1000 × 109/L). All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications). Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis. These patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms. Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia., Conclusions and Relevance: PV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant. PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD)., Methods: We analyzed whole-exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes., Results: Older UC patients (age > 45) harbored increased myeloid-CHIP mutations compared to younger patients (age ≤ 45) (P = .01). Lymphoid-CHIP was more prevalent in older IBD patients (P = .007). Young CD patients were found to have myeloid-CHIP with high-risk features. Inflammatory bowel disease patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP (P = .05), while anti-TNF therapy was associated with decreased myeloid-CHIP (P = .03). Pathway enrichment analyses indicated an overlap between CHIP genes, IBD phenotypes, and inflammatory pathways., Conclusions: Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles, especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease, and acceleration of their inflammatory disease., (© The Author(s) 2025. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was approved by the US Food and Drug Administration in 2014 for treatment of patients with polycythemia vera (PV) who have an inadequate response to or intolerance of hydroxyurea (HU). PV is a chronic myeloproliferative neoplasm defined by primary absolute erythrocytosis, bone marrow hypercellularity, and JAK mutations such as JAK2V617F. Patients with PV experience burdensome symptoms and are at risk of thromboembolic events, in particular those with resistance to or intolerance of initial treatments such as HU. Other risks for patients with PV include progression of disease to more aggressive forms with worse prognoses, such as myelofibrosis or blast-phase myeloproliferative neoplasms. This review summarizes the efficacy and safety of ruxolitinib from key phase 2 and 3 trials (MAJIC-PV, RESPONSE, RESPONSE-2, RELIEF, and Ruxo-BEAT), large real-world studies, and a decade of postmarketing surveillance safety data. The authors focus on improved blood count control, rates of thromboembolic events, symptom improvement, and markers of disease modification such as reduction of JAK2V617F allele burden in patients treated with ruxolitinib. They also discuss the well-characterized safety profile of ruxolitinib regarding hematologic and other adverse events of interest. In the 10 years since its approval, ruxolitinib remains a safe and effective standard-of-care treatment for PV. As the treatment landscape for PV continues to evolve in the coming years, the efficacy and safety profiles of ruxolitinib suggest it will remain a preferred treatment as monotherapy and as a potential backbone of future combination regimens., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Despite the study of BCR::ABL1-positive and -negative myeloproliferative neoplasms (MPNs) providing seminal insights into cancer biology, tumor evolution and precision oncology over the past half century, significant challenges remain. MPNs are clonal hematopoietic stem cell-derived neoplasms with heterogenous clinical phenotypes and a clonal architecture which impacts the often-complex underlying genetics and microenvironment. The major driving molecular abnormalities have been well characterized, but debate on their role as disease-initiating molecular lesions continues. The introduction of the ABL1 tyrosine kinase inhibitors have been extremely successful in the treatment of chronic myeloid leukemia with most patients having a near-normal life expectancy. Similar success has, however, not been achieved for BCR::ABL1-negative MPNs in terms of disease course modification and most patients remain incurable. In both disease categories, genomic instability seems to increase the risk of disease progression to accelerated/blast phase, which is resistant/refractory to conventional treatment and associated with a poor prognosis. To address some of these issues, the late John Goldman and Tariq Mughal founded a scientific and clinical platform in 2006, the Post-American Society of Hematology (ASH) MPN workshop, to appraise novel cancer biology, candidate therapeutic targets, treatments and other clinical challenges and pay tribute to all the many scientists and clinicians around the world instrumental to the progress made and continuing advances being made. This paper summarizes some of the recent data discussed at the 18 th edition of the workshop and includes reference to some data presented or published after the workshop, including the 26 th John Goldman CML conference., (© 2025 John Wiley & Sons Ltd.)

Competing Interests: Competing interests DT received research funding from Sobi, Sumitomo, Cogent Biosciences and Gilead and honoraria from Sobi, Novartis, AbbVie, PharmaEssentia, Sierra Oncology, GSK and Cogent Biosciences. CDD received honoraria from Abbvie, AstraZeneca, BMS, Genentech, GenMab, GSK, Immunogen, Notable Labs, Rigel, Schrodinger, and Servier and grant support from LLS Scholar in Research Award. TMK received research funding from AbbVie and Genentech and honoraria from AbbVie. FR received research funding from AbbVie and BMS and honoraria from AbbVie and BMS. AM received research funding from BMS, Incyte and Novartis. AA received research funding from Novartis, BMS, Onconova, Medimmune, Ariad, GSK, Celgene, Eisai, ALX Oncology, H3B Biomedicine/Hemavant. MK has received honoraria from Protagonist, Silence Therapeutics, Morphosys, Incyte, AbbVie and Kura. JF received research funding from Oryzon Genomics, Taiho Oncology, and Syros. RK received research funding from BMS and honoraria from Abbvie, BMS, DSI, Geron, Janssen, Jazz, PharmaEssentia, Rigel, Servio, Sobi, and Sumitomo. JM received research funding from Incyte, BMS, Novartis, Abbvie, Geron, Kartos, Karyopharm, Sobi and PharmaEssentia and honoraria from Incyte, BMS, Abbvie, Kartos, Geron, GSK, Roche, Merck, Pfizer, PharmaEssentia, MorphoSys, Novartis, Galecto, Sobi, Sumitomo, and Karyopharm. EP received research funding from Incyte, BMS, and Blueprint and honoraria from BMS, GSK, Sobi, Blueprint, Taiho, PharmaEssentia. DAS received research funding from Aprea and Jazz and honoraria from AbbVie, Aprea, Agios, Celyad, Froghorn, Gilead,Incyte, Intellisphere LLC, Kite, Megenta, Novartis, AvenCell, Astellas, BlueBird Bio, BMS, Dark Blue Therapeutics, Intellia, Jasper Therapeutics, Kite, Magenta Therapeutics, NKARTA, Novartis, Orbital Therapeutics, Rigel Pharmaceuticals, Shattuck Labs, Servier, Syndax, and Syros. MMP received research funding from Stemline, Kura Oncology, Solu Therapeutics, Epigenetix and Polaris Pharmaceuticals. GMB received research funding from IFM Therapeutics, Takeda Oncology, Solu Theraputics. The remaining of the authors have no potential competing interests to disclose. Ethics approval and consent to participate This study received approval by the Institutional Review Boards from all participating institutions and research was conducted in accordance with the Declaration of Helsinki. Given the retrospective nature of this analysis, informed consent was not required by local regulatory authorities.

Abstract: With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: This study examines the trends of procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), and sequential organ failure assessment (SOFA) scores in intensive care unit (ICU) sepsis patients from different infection sources. Elevations in PCT and NLR reflect infection severity and predict sepsis prognosis. Combining them may enhance diagnostic accuracy and prognostic capabilities, despite variations in cut-off values. The study emphasizes the significance of these biomarkers in improving sepsis management and patient outcomes., Materials and Methods: This was a prospective observation study of ICU sepsis patients from different infection sources. Procalcitonin and NLR levels were measured on days 0, 2, and 4 of admission. Sequential organ failure assessment scores on these days were also analyzed. The cut-off values were obtained for predicting the prognosis of sepsis ICU patients., Results: The study included 100 sepsis patients with an equal distribution of males and females and a mean age of 72 years. Procalcitonin showed a significant decrease over time, while NLR initially increased before decreasing on day 4, and SOFA scores showed no significant changes. Deceased patients had significantly higher PCT and SOFA scores on days 2 and 4. Receiver operating characteristic curve analysis showed promising predictive results for PCT on day 4 and SOFA scores on days 2 and 4., Conclusion: Understanding the trends of PCT and NLR concerning the infection source can provide deeper insights into their diagnostic and prognostic capabilities. This comparative analysis of PCT, NLR, and SOFA score trends contributes to the improvement of patient outcomes through accurate assessment of sepsis severity and progression, early diagnosis, and timely intervention., How to Cite This Article: Jayara A, Mascarenhas J, Gandhi B, Nimbolkar J. Comparison of Trends of Procalcitonin and Neutrophil to Lymphocyte Ratio in Patients of Sepsis in Intensive Care Unit. Indian J Crit Care Med 2024;28(10):942-951., Competing Interests: Source of support: Nil Conflict of interest: NoneConflict of interest: None, (Copyright © 2024; The Author(s).)

Background: Chronic myelomonocytic leukemia (CMML) is a rare and likely underdiagnosed hematologic malignancy. Due to its rarity and nuances in diagnosis, many patients are referred to tertiary referral centers, although many continue to be cared for in the community setting. Given discrepancies in outcomes based on facility type in related myeloid malignancies, we hypothesized that CMML patients treated at academic centers may have improved survival as compared to patients treated at nonacademic centers (NACs)., Patients and Methods: Using the National Cancer Database (NCDB), we identified 6290 patients with CMML and collected data on demographics, comorbidities, treatment, and survival. We also performed a propensity matched analysis to control for baseline differences., Results: We found that patients at academic centers had higher median overall survival (OS) (17.7 months vs 14.7 months) and 5-year OS (19.1% vs 15.3%) than patients at NACs. In addition, patients treated at an academic center were also more likely to receive hematopoietic stem cell transplant as compared to those treated at NACs. Time to treatment initiation was overall similar between academic and NACs., Conclusion: Our study of one of the largest available datasets of CMML patients supports the importance of referring CMML patients to academic centers upon diagnosis to optimize outcomes in this rare hematologic malignancy., Competing Interests: Disclosure All authors have completed the ICMJE uniform disclosure form. J.M. receives clinical research funding paid to his institution from Incyte, Novartis, Celgene/BMS, CTI Bio, Geron, AbbVie, PharmaEssentia, Kartos, and Karyopharm. He receives consulting fees from Incyte, CTI Bio, Novartis, Geron, Kartos, Karyopharm, MorphoSys, AbbVie, Celgene/BMS, PharmaEssentia, Pfizer, Imago, Merck, Roche, GSK, Galecto. D.T. receives clinical research funding paid to his institution from Astellas Pharma, Gilead, CTI Bio and consulting fees from GSH, CTI Bio, Novartis, AbbVie, Sierra Oncology, and Cogent Biosciences. J.F. receives clinical research funding from Oryzon and Syros Pharmaceuticals. S.T. has no disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Patients with myeloproliferative neoplasms (MPNs) face chronic symptom burden. Online symptom assessment studies allow for recruitment of large numbers of motivated patients, but patient self-selection can lead to sampling bias. This study evaluated how gender representativeness in MPN symptom surveys and trials impacted symptom score mean estimates, using data from 4825 survey respondents and 291 trial participants with MPNs. The survey data showed that men participated at a rate roughly 50% less than what would be expected based on prevalence, and women reported higher scores than men on average for six of 10 symptoms. Together, this led to potential over estimation in six of 10 symptom score means (ranging from 5.8% to 15.3% overestimated). The trial data showed less gender-based sampling bias compared to the survey data. Studies utilizing online symptom surveys should implement study design features to recruit more men, assess for gender participation imbalances, and provide weighted estimates where appropriate.

Advanced systemic mastocytosis (AdvSM) is a rare hematologic malignancy with organ damage and compromised life expectancy arising from organ accumulation of neoplastic mast cells. Identification of the gain-of-function KIT D816V in the majority of cases has accelerated pharmaceutical development culminating with the development of selective KIT inhibitors such as avapritinib. While the advent of these therapies has improved the quality and quantity of life in patients with AdvSM, current challenges remain in the management of this disease. In this review, we summarize the present and future therapeutics landscape of AdvSM, highlighting the development of novel KIT inhibitors including elenestinib and bezuclastinib. We also explore the continued role of additional treatment modalities including allogeneic stem cell transplantation before discussing unresolved clinical challenges in the management of AdvSM., Competing Interests: DT received research funding from Sobi, Sumitomo, Cogent Biosciences and Gilead and honoraria from Sobi, Novartis, AbbVie, PharmaEssentia, Sierra Oncology, GSK and Cogent Biosciences. JM received research funding from Incyte, BMS, Novartis, AbbVie, Geron, Kartos, Karyopharm, CTI/Sobi and PharmaEssentia and honoraria from Incyte, Blueprint Medicines, Keros, DISC Medicines, BMS, AbbVie, Kartos, Geron, GSK, Roche, Merck, Pfizer, PharmaEssentia, MorphoSys, Novartis, Galecto, Sobi, Sumitomo, and Karyopharm. The authors report no other conflicts of interest in this work., (© 2024 Tremblay et al.)

Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed., (© 2024. The Author(s).)

Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of somatic mutations in myeloid and lymphoid malignancy genes in the blood cells of individuals without a hematologic malignancy. Inflammation is hypothesized to be a key mediator in the progression of CHIP to hematologic malignancy and patients with CHIP have a high prevalence of inflammatory diseases. This study aimed to identify the prevalence and characteristics of CHIP in patients with inflammatory bowel disease (IBD). We analyzed whole exome sequencing data from 587 Crohn's disease (CD), 441 ulcerative colitis (UC), and 293 non-IBD controls to assess CHIP prevalence and used logistic regression to study associations with clinical outcomes. Older UC patients (age>45) harbored increased myeloid-CHIP mutations compared to younger patients (age≤45) ( p =0.01). Lymphoid-CHIP was more prevalent in older IBD patients ( p =0.007). Young CD patients were found to have myeloid-CHIP with high-risk features. IBD patients with CHIP exhibited unique mutational profiles compared to controls. Steroid use was associated with increased CHIP ( p =0.05), while anti-TNF therapy was associated with decreased myeloid-CHIP ( p =0.03). Pathway enrichment analyses indicated overlap between CHIP genes, IBD phenotypes, and inflammatory pathways. Our findings underscore a connection between IBD and CHIP pathophysiology. Patients with IBD and CHIP had unique risk profiles especially among older UC patients and younger CD patients. These findings suggest distinct evolutionary pathways for CHIP in IBD and necessitate awareness among IBD providers and hematologists to identify patients potentially at risk for CHIP-related complications including malignancy, cardiovascular disease and acceleration of their inflammatory disease., Competing Interests: J.M reports receiving consulting fees from Incyte, SOBI, Novartis, Geron, AbbVie, Bristol Myers Squibb, GSK, MorphoSys, Galecto, Disc, Pfizer, Merck, Keros and PharmaEssentia; receiving research support from Incyte, SOBI, Geron, BMS, PharmaEssentia, AbbVie, Novartis, Kartos and Ajax. R.H reports receiving consulting fees from Potagonaist Therapeutics and Silence Therapeutics; receiving research support from Kymera, Karyopharm, Cellinkos, Kartos, and Dexcel Therapeutics. L.J.C. reports receiving consulting fees from Orchard Therapeutics and ORGANOIDSCIENCES; receiving research grants from Bristol Myers Squibb; receiving payment for lectures from Ferring Pharmaceuticals and Takeda. B.K.M reports receiving consulting fees from Cellarity. All other authors have no disclosures. No authors have any conflicts of interest to declare.

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.

Patients with inflammatory bowel disease (IBD) are exposed to chronic systemic inflammation and are at risk for secondary malignancies. Here we review the literature on the risk of myeloid neoplasms (MN) in IBD and present the disease profiles of patients at a single institution with IBD who later developed MN, comparing them to those in the literature. No IBD characteristic was found to associate with MN disease severity, including the previously-identified association between MNs and thiopurine exposure. Of the somatic mutations identified in out cohort's MN, mutations in TET2 were most prevalent, followed by FLT3-ITD, BCR-ABL , and NPM1 mutations., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Limited data exist regarding the role of multimodal prehabilitation during neoadjuvant chemotherapy (NACT) for breast cancer. Determining large trial feasibility and identifying signals of prehabilitation benefit are needed., Patients and Methods: We conducted a randomized controlled feasibility trial of multimodal prehabilitation versus usual care during NACT among women diagnosed with non-metastatic breast cancer. Intervention participants received an individualized exercise program, dietetic support, and stress management counseling during NACT. The trial assessed feasibility via rates of recruitment, attrition, adherence, and study-related adverse events. Physical fitness (Six Minute Walk Test, grip strength, anthropometrics) and patient-reported outcomes were assessed at baseline, after NACT completion, and 6 months after surgery as exploratory outcomes, and analyzed using linear mixed effects models. Qualitative data were collected from a subsample to understand feasibility and acceptability of prehabilitation., Results: A total of 72 participants were enrolled from the 123 eligible patients (recruitment rate of 53%). There was a 13% attrition rate and no intervention-related adverse events. Participants in the prehabilitation group had better 6-min walk distance at the post-chemotherapy timepoint [between group difference of 49.43 m, 95% confidence interval (CI) - 118.1, 19.2] and at the post-surgery timepoint (27.3, 95% CI -96.8, 42.2) compared with the control group. Prehabilitation participants reported better quality of life, less fatigue, and improved physical activity levels compared with usual care participants. Interviews revealed that the intervention had a positive impact on the treatment experience., Conclusions: This study demonstrated feasibility and improvement in physical and psychosocial outcomes. Larger trials assessing intervention efficacy to confirm indications of prehabilitation benefit are warranted., (© 2024. Society of Surgical Oncology.)

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy., Competing Interests: PV: Consulting fees (AbbVie, Amgen, Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma Corp, Daiichi Sankyo, GlaxoSmith Kline, Karyopharm, Novartis, Pfizer, Genentech, Servier, Stemline, MorphoSys, LAVA Therapeutics); honoraria for lectures/advisory boards (Incyte, Blueprint Medicines, CTI Biopharma). JM: Grants (PharmaEssentia, Novartis, Roche, Geron, Abbie, Kartos, Karyopharm); consulting fees (PharmaEssentia, CTI, Incyte, Roche, Novartis, Merck, Geron, AbbVie, BMS, Kartos, MorphoSys, Galecto, Imago); honoraria for lectures/advisory boards (BMS); monitoring or advisory board (Incyte, Galecto); meeting/travel support (Kartos). PB: Grants (Incyte, CTI, MorphoSys, Kartos, Telios, Ionis, Disc, Blueprint, Cogent, Geron, Janssen, Sumitomo, BMS, Karyopharm); consulting fees (Incyte, BMS, CTI, GSK, AbbVie, MorphoSys, Karyopharm, PharmaEssentia, Blueprint, Cogent, Novartis, Jubilant, Morphic, Ono, Sumitomo); honoraria for lectures/advisory boards (Incyte, Blueprint, GSK, CTI, AbbVie, Sumitomo, PharmaEssentia). GH: Grants (Incyte); consulting fees (PharmaEssentia, Protagonist, AbbVie, GSK, Pfizer, Novartis, MorphoSys, Cogent, Pharmaxis); monitoring or advisory board (PharmaEssentia, Protagonist, AbbVie, GSK, Pfizer, Novartis, MorphoSys); stock/stock options (Regeneron Pharmaceuticals). AY: Consulting fees (Incyte, CTI Pharma, PharmaEssentia, Pfizer, Novartis, Acceleron Pharma, Servier, AbbVie, Apellis, Gilead, Notable Labs); meeting/travel support (Incyte). JMP: Consulting fees (Sierra Oncology, MorphoSys, CTI, Protagonist). ATG: Consulting fees (PharmaEssentia, MorphoSys, CTI, Biopharma, Bristol-Meyers Squibb, Sierra Oncology/GSK, Kartos, AbbVie, Imago Biosciences). LM: Advisory board (MorphoSys). ATK: Grants (BMS, Protagonist, Janssen, GSK, MorphoSys); consulting fees (GSK, AbbVie, Incyte); honoraria for lectures/advisory boards (PharmaEssentia, Novartis, BMS); monitoring or advisory board (Incyte). RKR: Grants (Incyte, Ryvu, MorphoSys, Zentalis); consulting fees (MorphoSys, CTI, GSK, Stemline, Blueprint, SDP, Servier, Zentalis, BMS, Galectco, AbbVie, PharmaEssentia, Cogent, Kartos); honoraria for lectures/advisory boards (Protagonist, Karyopharm, GSK); monitoring or advisory board (Kartos). RM: Consulting fees (Incyte, PharmaEssentia, CTI, AbbVie, GSK, BMS, Genentech). SV: The author declares that there is no conflict of interest., (© The Author(s), 2024.)

The Society for Cardiovascular Angiography & Interventions (SCAI) endeavors to serve the interventional cardiology community, including both clinicians and patients. The SCAI Scientific Oversight Committee is charged with annually reviewing the scientific needs of the membership at large, including survey-based research of the practice patterns and perspectives of SCAI members and stakeholders. This document is intended as a reference by the survey proponents, document writing groups, external collaborators, SCAI representatives, peer reviewers, and anyone seeking information about the SCAI surveys program. The aims of this SCAI document are to: (1) provide a framework for members to develop survey requests that are relevant, feasible, and align with the Society's missions and goals; (2) promote transparency and clarity for the process of performing a survey through SCAI; (3) establish the criteria for evaluating survey requests and provide input on reliable and meaningful design, data collection, and best practices; and (4) facilitate collaboration and communication between the survey committee and members of SCAI to maximize the impact of the findings to the interventional community at large., (© 2023 The Author(s).)

ABSTRACT Myeloproliferative neoplasms (MPNs) that lack the classical "driver mutations," termed triple negative MPNs, remain a poorly understood entity. Despite considerable progress toward understanding MPN pathobiology, the mechanisms leading to the development of these MPNs remains inadequately elucidated. While triple negative primary myelofibrosis (TN-PMF) portends a poor prognosis, triple negative essential thrombocythemia (TN-ET) is more favorable as compared with JAK2 mutated ET. In this review, we summarize the clinical features and prognosis of TN-PMF and -ET as well as diagnostic challenges including identification of non-canonical driver mutations. We also discuss additional molecular drivers to better understand possible pathogenic mechanisms underlying triple negative MPNs. Finally, we highlight current therapeutic approaches as well as novel targets, particularly in the difficult to treat TN-PMF population.

Background: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice., Patients and Methods: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment., Results: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01)., Conclusion: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib., Competing Interests: Disclosure J.M. reports research funding paid to institution from AbbVie, BMS, CTI BioPharm, Geron, Incyte, Kartos, Novartis, PharmaEssentia, and Roche; consulting fees from AbbVie, BMS, CTI BioPharm, Galecto, Geron, GSK, Incyte, Kartos, Karyopharm, MorphoSys, Novartis, PharmaEssentia, Roche, and Sierra Oncology. C.H. reports research funding from BMS/Celgene, Constellation Pharmaceuticals, a MorphoSys Company, and Novartis; and advisory role and speaker funding from Abbvie, AOP Orphan Pharmaceuticals, BMS/Celgene, CTI BioPharma, Galacteo, Geron, Gilead, Janssen, Keros, Novartis, Promedior, Roche, and Shire. T.A.S., D.L., M.G., and T.A.M. report employment with Cardinal Health. S.M. and A.M. report employment with BMS. D.T. and I.S.D. report employment with and stock ownership in BMS. P.A. reports no conflicts of interest. J.K. reports employment with and stock ownership in Cardinal Health at the time this study was conducted. B.A.F. reports research funding from BMS; and stock ownership in and employment with Cardinal Health. A.T.G. reports consulting for AbbVie, BMS/Celgene, CTI BioPharma, Constellation Pharmaceuticals, a MorphoSys Company, GSK/Sierra Oncology, Incyte, Kartos, Novartis, and PharmaEssentia., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication., Competing Interests: Declaration of Competing Interest JM has received research funding paid to the institution from Novartis, CTI, Incyte, BMS, Geron, Abbvie, Kartos and PharmaEssentia and consulting fees from Incyte, CTI Bio, Novartis, Roche, GSK, Sierra Onc, PharmaEssentia, Kartos, Karyopharm, Galecto, Imago, BMS, Abbvie and Geron. DT has received research funding paid to his institution from CTI Biopharma, Astellas Pharma and Gilead and consulting fees from CTI Biopharma, Novartis, AbbVie, Sierra Oncology, GSK and Cogent. The other authors have no competing interests to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics., Methods: The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012 and 2022 that were phase 1, 2, or 3 and relevant trial characteristics were extracted., Results: 1,270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p &lt; 0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p &lt; 0.01). Phase 3 trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase 1 and 2 trials that had higher rates of excluding patients with only active CNS involvement (p &lt; 0.01)., Conclusion: A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active but also with any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials., (© 2023 S. Karger AG, Basel.)