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Background: Intrasaccular devices have broadened treatment options for wide necked aneurysms. This study presents the preliminary experience with the Artisse 2.0 device., Methods: Innovative NeurovaScular Product SurveIllance REgistry (INSPIRE) is a non-randomized, multicenter, real world clinical study with treatment arms for aneurysms (INSPIRE-A) and acute ischemic stroke (INSPIRE-S). This interim analysis included 87 patients enrolled from November 2022 to April 2024 in the INSPIRE-A Artisse cohort across 16 Europoean centers. Procedures followed standard clinical care, with 6 months of follow-up. Safety and efficacy endpoints included major stroke, neurological death, serious adverse events (SAEs), aneurysm occlusion, and retreatment rates. An independent core laboratory assessed imaging, and all SAEs were reviewed by a clinical events committee. The Artisse steering committee provided independent oversight of the data., Results: The Artisse device achieved an overall successful implantation rate of 96.6% (84/87), with satisfactory placement rates of 98.7% (74/75) for unruptured and 88.9% (8/9) for ruptured aneurysms. Following the procedure, 46.2% of unruptured aneurysm patients were receiving antiplatelet therapy (APT), predominantly aspirin monotherapy, while no ruptured aneurysm patients received APT. Device related SAE rate was 1.3% (1/87), and the overall stroke rate was 2.3% (2/87), including both ruptured and unruptured aneurysms. At 6 months, 80.0% (28/35) of patients with unruptured aneurysms showed complete obliteration, with no recurrences or retreatments., Conclusions: Preliminary experience with the Artisse 2.0 device demonstrated high technical success, favorable safety, and efficacy in aneurysm obliteration at 6 months. Larger studies with longer follow-up periods are needed to confirm these findings., Competing Interests: Competing interests: VC is a consultant for Medronic and recipient of research grants from Medtronic. MK-O is a consultant for Medronic and part of the steering committee for Innovative NeurovaScular Product SurveIllance REgistry-Aneurysm (INSPIRE-A). RR has consulting agreements with Stryker, Balt, Medtronic, Microvention, and Acandis, and is part of the steering committee for INSPIRE-A . SL receives honoraria from Medtronic in relation to proctoring, speaking, and consulting, and is part of the steering committee for INSPIRE-A. LS is a consultant for Balt, Microvention, Medtronic, Stryker, and Cerenovus; receives research consultancy fees from Medtronic to attend steering committee meetings; and is part of the steering committee for INSPIRE-A. JF is part of the steering committee for INSPIRE-A and is consultant for Medtronic. MAM received research grants from Medtronic and Stryker, is part of the steering committee for INSPIRE-A, and is a consultant for Cerenovus and Siemens., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Objectives: We studied the short- and long-term effects of imatinib in hospitalized COVID-19 patients., Methods: Participants were randomized to receive standard of care (SoC) or SoC with imatinib. Imatinib dosage was 400 mg daily until discharge (max 14 days). Primary outcomes were mortality at 30 days and 1 year. Secondary outcomes included recovery, quality of life and long COVID symptoms at 1 year. We also performed a systematic review and meta-analysis of randomized trials studying imatinib for 30-day mortality in hospitalized COVID-19 patients., Results: We randomized 156 patients (73 in SoC and 83 in imatinib). Among patients on imatinib, 7.2% had died at 30 days and 13.3% at 1 year, and in SoC, 4.1% and 8.2% (adjusted HR 1.35, 95% CI 0.47-3.90). At 1 year, self-reported recovery occurred in 79.0% in imatinib and in 88.5% in SoC (RR 0.91, 0.78-1.06). We found no convincing difference in quality of life or symptoms. Fatigue (24%) and sleep issues (20%) frequently bothered patients at one year. In the meta-analysis, imatinib was associated with a mortality risk ratio of 0.73 (0.32-1.63; low certainty evidence)., Conclusions: The evidence raises doubts regarding benefit of imatinib in reducing mortality, improving recovery and preventing long COVID symptoms in hospitalized COVID-19 patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanna-Riikka Kreivi is a consultant for Pfizer and Roche and received lecture honoraria from Pfizer. Tiina Mattila is an advisory board member for GSK and received lecture honoraria from AstraZeneca, Boehringer-Ingelheim, Chiesi, GSK, and Orion. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Physician variablity in preoperative planning of endovascular implant deployment and associated inaccuracies have not been documented. This study aimed to quantify the variability in accuracy of physician flow diverter (FD) planning and directly compares it with PreSize Neurovascular (Oxford Heartbeat Ltd) software simulations., Methods: Eight experienced neurointerventionalists (NIs), blinded to procedural details, were provided with preoperative 3D rotational angiography (3D-RA) volumetric data along with images annotated with the distal landing location of a deployed Surpass Evolve (Stryker Neurovascular) FD from 51 patient cases. NIs were asked to perform a planning routine reflecting their normal practice and estimate the stent's proximal landing using volumetric data and the labeled dimensions of the FD used. Equivalent deployed length estimation was performed using PreSize software. NI- and software-estimated lengths were compared with postprocedural observed deployed stent length (control) using Bland-Altman plots. NI assessment agreement was assessed with the intraclass correlation coefficient (ICC)., Results: The mean accuracy of NI-estimated deployed FD length was 81% (±15%) versus PreSize's accuracy of 95% (±4%), demonstrating significantly higher accuracy for the software (p<0.001). The mean absolute error between estimated and control lengths was 4 mm (±3.5 mm, range 0.03-30.2 mm) for NIs and 1 mm (±0.9 mm, range 0.01-3.9 mm) for PreSize. No discernable trends in accuracy among NIs or across vasculature and aneurysm morphology (size, vessel diameter, tortuousity) were found., Conclusions: The study quantified experienced physicians' significant variablity in predicting an FD deployment with current planning approaches. In comparison, PreSize-simulated FD deployment was consistently more accurate and reliable, demonstrating its potential to improve standard of practice., Competing Interests: Competing interests: ATR, SB: consulting agreement Stryker, Cerenovus, Microvention. JD: PI for Oxford Heartbeat Multicentre Prospective Oxford Heartbeat PreSize study; consulting agreement Stryker, Phenox, Microvention, Oxford Endovascular. VCdN, CG: consulting agreement Stryker, Medtronic. RR: consulting agreement Stryker, Balt, Medtronic, Microvention, Acandis. JP, TP, MS, JDP: no disclosures., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: High sodium intake is an accepted risk factor for hypertension, while low Na + intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na + excretion with haemodynamics and volume status., Materials and Methods: Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na + excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism., Results: The mean values of 24-h urinary Na + excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4-44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na + excretion. In regression analysis, body surface area and 24-h Na + excretion were independent explanatory variables for extracellular water volume. No differences in urine Na + excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water ( p  = .003), and 24-h Na + excretion was not related with extracellular water volume., Conclusion: In the absence of mineralocorticoid excess, Na + intake, as evaluated from 24-h Na + excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.

The incidence of venous thromboembolism (VTE) for non-hospitalised patients with coronavirus disease-2019 infection has not been very widely studied. 13 019 persons with a positive SARS-CoV-2 nucleic acid amplification test were identified. In total, 447 (0.2%) VTEs were identified in the study population, 293 (66%) of these were pulmonary embolisms. A positive SARS-CoV-2 test did not increase the risk for VTE in the univariate analysis (odds ratio (OR): 1.0, 95% confidence interval (CI): 0.69-1.4) or multivariable analysis (OR: 1.36, 95% CI: 0.93-1.97)., (© 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Objectives: The Puumala virus (PUUV) is a hantavirus that causes hemorrhagic fever with renal syndrome. Studies showing an increased risk of lymphoid malignancies after hantavirus infection, together with the observation that PUUV infects B cells, motivated us to study the risk of lymphoid malignancies after PUUV infection., Methods: We linked data from the Finnish Cancer Registry and National Infectious Diseases Register for 2009-2019. We used a time-dependent Cox regression model to evaluate the hazard of the lymphoid malignancies grouped according to the HAEMACARE classification., Results: We identified 68 cases of lymphoid malignancies after PUUV infection among 16,075 PUUV-infected individuals during 61,114,826 person-years of observation. A total of 10 cases occurred within 3-<12 months and 38 within 1-<5 years after PUUV infection, and the risk of lymphoid malignancies increased with hazard ratios (HRs) of 2.0 (95% confidence interval [CI], 1.1-3.7) and 1.6 (95% CI, 1.2-2.3), respectively. The group of mature B cell neoplasms showed an increased risk 3-<12 months and 1-<5 years after PUUV infection, HR 2.2 (95% CI, 1.2-4.3) and HR 1.8 (95% CI, 1.3-2.5), respectively., Conclusion: PUUV infection is associated with lymphoid malignancies in the Finnish population, supporting the earlier studies. Further research is required to understand the pathophysiological mechanisms behind this association., Competing Interests: Declaration of competing interest TD works in Monitoring Outbreaks for Disease surveillance in a data science context (MOOD)/Horizon 2020 project, for which funding is received from the Finnish Institute for Health and Welfare and is a member of the executive board of MOOD Horizon 20202. TD also works on a project for vector-borne diseases and climate change in Finland (VECLIMIT), for which funding is received by the Finnish Institute for Health and Welfare from the Academy of Finland. JS owns stocks in a company (Genmab) that is involved in lymphoma drug development. EK reports a grant paid for their institution from the Finnish Society of Sciences and Letters for PUUV research outside of the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Transradial access (TRA) has increased popularity among neurointerventionalists during a short time period but until recently there have been no devices designed especially for radial use., Materials and Methods: Consecutive neurointerventional procedures with an intention to perform TRA with the Rist radial access guide catheter between April 2021 and May 2022 were retrospectively reviewed. Possible access site complications, other procedure-related complications and information on successful catherization of the target vessel as well as whether the procedure had been successful were collected., Results: Information from 100 patients was included in the study. The most general procedure was flow diversion (29%) followed by WEB embolization (20 %). Four patients (4%) needed conversion to femoral access. The triaxial system was used in 76% of the procedures. Four patients (4%) experienced access site or device related complications, none of those were serious. Six patients had clinically relevant procedure related complications., Conclusions: It is concluded that the Rist device can be used safely for a large variety of neurointerventions with a short learning curve., 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 © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Flow diversion is an innovative and increasingly used technique for the treatment of intracranial aneurysms. New flow diverters (FDs) are being introduced to improve the safety and efficacy of this treatment. The aim of this study was to assess the safety, feasibility, and efficacy of the new Pipeline Vantage (PV) FD., Methods: Patients with intracranial aneurysms treated with the PV at 10 international neurovascular centers were retrospectively analyzed. Patient and aneurysm characteristics, procedural parameters, complications, and the grade of occlusion were assessed., Results: 60 patients with 70 aneurysms (5.0% with acute hemorrhage, 90.0% located in the anterior circulation) were included. 82 PVs were implanted in 61 treatment sessions. The PV could be successfully implanted in all treatments. Additional coiling was performed in 18.6%, and in-stent balloon angioplasty (to enhance the vessel wall apposition) in 24.6%. Periprocedural technical complications occurred in 24.6% of the treatments, were predominantly FD deployment problems, and were all asymptomatic. The overall symptomatic complication rate was 8.2% and the neurological symptomatic complication rate was 3.3%. Only one symptomatic complication was device-related (perforator artery infarctions leading to stroke). After a mean follow-up of 7.1 months, the rate of complete aneurysm occlusion was 77.9%. One patient (1.7%) died due to aneurysmal subarachnoid hemorrhage which occurred before treatment, unrelated to the procedure., Conclusions: The new PV FD is safe and feasible for the treatment of intracranial aneurysms. The short-term occlusion rates are promising but need further assessment in prospective long-term follow-up studies., Competing Interests: Competing interests: DFV has received travel support outside this work from MicroVention and Stryker GmbH & Co. KG. SC is shareholder of NDI Technologies and Vesalio LLC, non-paid member of Siemens Senior Advisory Board, and reports consultancy proctorship agreements with Medtronic and MicroVention. IS reports consultancy and proctorship agreements with Medtronic and MicroVention, and is Associate Editor for JNIS. RR is consultant for Stryker Neurovascular, Medtronic, MicroVention and Acandis. MMG is consultant and proctor for Medtronic. VMP is consultant for Medtronic. MB reports board membership: DSMB Vascular Dynamics; consultancy: Roche, Guerbet, Codman; grants/grants pending: DFG, Hopp Foundation, Novartis, Siemens, Guerbet, Stryker, Covidien; payment for lectures (including service on speakers bureaus): Novartis, Roche, Guerbet, Teva, Bayer, Codman. MM has received consulting honoraria, speaker honoraria, and travel support outside this work from Codman, Covidien/Medtronic, MicroVention, Phenox, and Stryker., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Perimesencephalic and nonperimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-naSAH and NPM-naSAH) have a different bleeding pattern and clinical course. The etiology and risk factors for PM-naSAH and NPM-naSAH are unclear. The objective of this study was to compare risk factors and triggering events between PM-naSAH and NPM-naSAH., Methods: We reviewed retrospectively all patients (n = 3475) who had undergone cerebral digital subtraction angiography between 2003 and 2020 at our tertiary hospital. Of these, 119 patients had 6-vessel angiography negative subarachnoid hemorrhage (47 (39%) PM-naSAH and 72 (61%) NPM-naSAH) and accurate information about the triggering event was available in 42 (89%) PM-NASAH and 64 (89%) NPM-naSAH patients., Results: PM-naSAH were younger compared to NPM-naSAH (mean age [SD]; 55.3 [11.1] years vs. 59.6 [12.2] years, p = .045. PM-naSAH was triggered during the physical exertion in 79% of patients and 16% of patients with NPM-naSAH (relative risk 5.4; 95% CI, 2.9-10.1, p < .0001). There were no significant difference in sex, smoking, alcohol abuse, hypertension, diabetes, hyperlipidemia, or anticoagulation/antithrombotic usage between PM-naSAH and NMP-naSAH, p > .05., Conclusion: Physical exertion was a triggering factor in most of the PM-naSAH cases and the risk was five times greater than in NMP-naSAH. More studies are needed to confirm our results and to study pathophysiology of PM-naSAH and NPM-naSAH., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objectives: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy., Methods: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively., Results: A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p < .001)., Conclusions: Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Flow diversion of acutely ruptured intracranial aneurysms (IAs) is controversial due to high treatment-related complication rates and a lack of supporting evidence. We present clinical and radiological results of the largest series to date., Methods: This is a nationwide retrospective study of acutely ruptured IAs treated with flow diverters (FDs). The primary outcome was the modified Rankin Scale (mRS) score at the last available follow-up time. Secondary outcomes were treatment-related complications and the aneurysm occlusion rate., Results: 110 patients (64 females; mean age 55.7 years; range 12-82 years) with acutely ruptured IAs were treated with FDs between 2012 and 2020 in five centers. 70 acutely ruptured IAs (64%) were located in anterior circulation, and 47 acutely ruptured IAs (43%) were blister-like. A favorable functional outcome (mRS 0-2) was seen in 73% of patients (74/102). Treatment-related complications were seen in 45% of patients (n=49). Rebleeding was observed in 3 patients (3%). The data from radiological follow-ups were available for 80% of patients (n=88), and complete occlusion was seen in 90% of aneurysms (79/88). The data from clinical follow-ups were available for 93% of patients (n=102). The overall mortality rate was 18% (18/102)., Conclusions: FD treatment yields high occlusion for acutely ruptured IAs but is associated with a high risk of complications. Considering the high mortality rate of aneurysmal subarachnoid hemorrhage, the prevention of rebleeding is crucial. Thus, FD treatment may be justified as a last resort option., Competing Interests: Competing interests: KA has received personal research grants from Turku University Foundation and Maire Taponen Foundation. RRaj has received personal research grants from Finska Läkaresällskapet and Medicinska Understödsföreningen Liv & Hälsä. RR is consultant for Microvention, Stryker and Medtronic., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Several studies have reported good long-term results in the occlusion of intracranial aneurysms with flow diverter treatment. The aim of this study was to report the safety and six-month follow-up outcomes using the new Surpass Evolve flow diverter in the treatment of intracranial aneurysms., Materials and Methods: Consecutive patients with intracranial aneurysm treated with Surpass Evolve flow diverter in two high-volume neurovascular centers between May 2019 and January 2020 were retrospectively reviewed. Procedure-related complications, aneurysm occlusion (O'Kelly-Marotta grading scale), and clinical outcomes were assessed., Results: Twenty-nine patients with 30 aneurysms were included in the study. Favorable aneurysm occlusion (O'Kelly Marotta grading scale C-D) at six-month follow-up was achieved in 21/27 (78%) aneurysms. No clinical procedure related thromboembolic complications were encountered. Twenty-three out of 24 patients with unruptured aneurysms treated with Surpass Evolve remained clinically intact at clinical follow-up. There was one fatal hemorrhagic procedure-related complication (3%). In five patients with ruptured aneurysms, no early or late rebleeds occurred from the aneurysms., Conclusions: Surpass Evolve FD worked technically well with no intraprocedural thromboembolic complications and occlusion rates comparable to other FDs., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: The aim was to identify the clinical characteristics, outcome, and antimicrobial susceptibility of healthcare-associated bloodstream infections (BSIs) in hematological patients., Methods: This retrospectively collected laboratory-based surveillance data include 3404 healthcare-associated BSIs in 2296 patients with a hematological malignancy in hospitals participating in the Finnish Hospital Infection Program from January 1, 2006, to December 31, 2016., Results: The most common underlying diseases were acute myelogenous leukemia (35%) and non-Hodgkin lymphoma (22%). Gram-positive organisms accounted for 60%-46% and gram-negative organisms for 24%-36% of BSIs in 2006-2016. The most common causative organism was coagulase-negative staphylococci (CoNS) (n = 731). The 7- and 28-day case fatality rates were 5.2% and 11.4%, respectively, and was highest in BSIs caused by Candida species (10.8% and 30.8%). The median age of patients increased from 59 years in 2006-2008 to 62 years in 2015-2016 (P < .01). Five percent of S aureus isolates were resistant to methicillin and five percent of Pseudomonas aeruginosa isolates were multidrug-resistant. Four percent of Klebsiella and seven percent of E coli isolates were resistant to ceftazidime., Conclusions: The proportion of gram-positive bacteria decreased and gram-negative bacteria increased over time. The case fatality rate was low and the median age of patients increased during the study., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: Stent-assisted treatment techniques can be an effective treatment option for intracranial aneurysms. The aim of this study was to evaluate the periprocedural feasibility and safety of the new LVIS EVO stent for the treatment of intracranial aneurysms., Materials and Methods: Patients with intracranial aneurysms treated with the LVIS EVO in 11 European neurovascular centers were retrospectively reviewed. Patient and aneurysm characteristics, procedural parameters, immediate grade of occlusion, and technical and clinical complications were assessed., Results: Fifty-seven patients with 59 aneurysms were treated with the LVIS EVO device; 57.6% of the aneurysms were incidental; 15.3% were acutely ruptured; 15.3% were recanalized or residual aneurysms; and 11.9% were treated for symptoms other than acute hemorrhage. The most frequent aneurysm locations were the middle cerebral artery (25.4%) and the anterior communicating artery (22.0%). The rate of immediate successful deployment was 93.2%. In 6.8% ( n = 4) of cases, additional in-stent angioplasty was needed. The immediate complete occlusion rate was 54.2%, while there was a residual aneurysm in 35.6% and a residual neck in 10.2%. Periprocedural technical complications occurred in 7/59 treatments (11.9%; the most frequent technical complication [ n = 3] was thrombus formation), which all resolved completely without clinical sequelae. Postprocedural neurologic complications occurred after 4/59 treatments (6.8%; 2 transient ischemic attacks, 1 minor stroke, 1 major stroke), of which only 1 persistent complication was directly related to the procedure (minor stroke in the vascular territory distal to the stent)., Conclusions: The LVIS EVO stent is a safe, feasible device for the treatment of intracranial aneurysms., (© 2021 by American Journal of Neuroradiology.)

Extradural internal carotid artery aneurysms are rare and the indications for treatment are not well defined. We report successful management of two high extradural internal carotid artery aneurysms treated with flow diverter stents. The endovascular repair of extradural internal carotid artery aneurysms is effective because with surgical treatment there is always the possibility of cranial nerve injury.

As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.

The 23-valent pneumococcal polysaccharide vaccine (PPV23) given alone is ineffective in patients with chronic lymphocytic leukemia (CLL) and better antibody response is achieved with pneumococcal conjugate vaccines (PCVs). In this study, we determine whether CLL patients would achieve a significant antibody response and broaden their serotype coverage against invasive pneumococcal disease (IPD) with PPV23 given five years after the 7-valent conjugate vaccine (PCV7). A total of 24 patients with CLL and eight controls were vaccinated with PPV23 five years after PCV7. Blood samples for evaluation of antibody response to PCV7 serotypes and PPV23 serotypes 5 and 7 were taken before vaccination and one month after it. Post-vaccination samples were available from 20 patients. IgG antibodies were measured with ELISA. Antibody concentrations after PPV23 were significantly lower in CLL patients for six of the PCV7 serotypes and for both PPV23 serotypes. Only 10% to 15% of CLL patients achieved an antibody response suggested to be protective against IPD. Hence, PCV7 given five years before PPV23 did not improve antibody response in patients with CLL. Based on our results, PPV23 given after a PCV primer is not useful against IPD in CLL patients.

Outcomes for patients with multiple myeloma (MM) have improved with the advent of novel therapies, however, real-world evidence of outcomes in clinical practice is scarce. We conducted a multi-center registry study to build a reliable picture of treatment and patient outcomes in Finland. The aim of this study was also to understand any methodological challenges in assessing treatment outcomes using disease registry data., Methods: We carried out a retrospective, observational study using data from the national Finnish Hematology Registry (FHR) to provide real-world evidence of outcomes for all adult patients diagnosed with and treated for MM between 2009-2013 at one of the six regional hospitals, with at least six months of recorded follow-up. Patients were identified within the FHR by applying eligibility criteria of a diagnosis of MM and verifiable records of medical treatment and lines of treatment during the study period. Patients receiving allogenic stem cell transplantation were excluded from the cohort, as were individuals who only had monoclonal gammopathy of undetermined significance diagnosis and patients who had not initiated treatment during this period. Kaplan Meier curves were used to calculate overall survival and time to next treatment. Stratification was carried out by drug status (conventional/novel) and by autologous stem cell transplant (ASCT) status., Results: A total of 321 patients met the inclusion criteria and were included in this study. Overall survival (OS) was longest in patients who received first-line novel therapy and ASCT (median not reached during 60-month follow-up) versus 46.2 months for novel first-line therapy without ASCT and 25.6 months for first-line conventional therapy without ASCT. Similarly, median time to next treatment were 33.9 months, 12.6 months and 7.8 months, respectively., Conclusions: The adoption of novel treatments in MM in Finland has had substantial impact on patient outcomes. Given the reality of complex treatment combinations for MM and relatively low patient numbers, assessing individual treatment effectiveness will require substantial cohort sizes and advanced, collaborative analytics on an international scale., Competing Interests: KR has been a member of Advisory Boards for Abbvie, Celgene, Janssen-Cilag and Takeda and has received fees to attend Congresses from Abbvie, Amgen, Celgene, Janssen-Cilag, Sanofi, Takeda. PA has been a member of Advisory Boards for Amgen, Celgene, Janssen and Takeda and has received fees to attend Congresses from Amgen, Bristol-Meyers-Squibb, Celgene, Janssen, Roche, Sanofi, Takeda and Teva. RS has received research funding from Amgen, BMS, Celgene, Janssen-Cilag and Takeda and honoraria from the same companies (Advisory Board and presentations). MP has received honoraria from Amgen, Celgene, Janssen-Cilag and Takeda (Advisory Board and presentations). HO does not have any competing interests. VT does not have any competing interests. MS does not have any competing interests. KK has received financial support from Jansen to collect data for this study and travel grants from Amgen, Shire and Sanofi Genzyme. TJ, MaP, FS, PCK and AL are employees of Janssen, the funder of this research. FW does not have any competing interests. TD is a Director of JB Medical and has worked with, and been funded by, other pharmaceutical companies in the field of hematological cancer. The funder Janssen provided support in the form of salaries for authors AL, PCK, TMJ, FS, MaP. This was a company sponsored study conducted in collaboration with the Finnish researchers, where both parties were involved in the study design, analysis and publication as per ICMJE standards. Data collection was carried out at the Finnish hospitals, with financial support from the funder. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Janssen funded JB Medical Ltd to provide medical writing support, TD is a paid employee of JB Medical and carried out the work. JB Medical did not have any additional role in the study design, data collection and analysis or decision to publish. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Heparin-induced thrombocytopenia (HIT) usually appears at 5 to 10 days after initiation of heparin. Autoimmune HIT can arise after discontinuation of heparin treatment (delayed-onset HIT) or without any preceding heparin exposure (spontaneous HIT syndrome)., Case Report: This case presents a course of autoimmune HIT with delayed onset. The patient was hospitalized due to influenza pneumonia and received low-molecular-weight heparin thromboprophylaxis for 9 days. Seven days after discharge, she was readmitted because of a cerebral sinus vein thrombosis and severe thrombocytopenia. Intracranial bleeding and brain infarction caused her death., Discussion: Autoimmune HIT was confirmed by functional heparin-induced platelet (PLT) activation test. Intracranial bleeding prevented continuous and effective anticoagulation. PLT transfusions were given, although they are generally advised against in HIT patients due to potential risk of thromboembolic events., Conclusion: This case presents that testing PLT-activating antibodies both in the presence and in the absence of current heparin treatment helps to diagnose patients with autoimmune HIT. There is conflicting evidence to refuse PLT transfusion when HIT is complicated with life-threatening bleeding., (© 2018 AABB.)

Patients with chronic lymphocytic leukemia (CLL) are at a high risk for infections caused by Streptococcus pneumoniae. A pneumococcal conjugate vaccine (PCV) can induce a significant antibody response for some CLL patients. In this study we investigated antibody persistence after PCV7 in patients with CLL. The study material comprised 24 patients with CLL and 8 immunocompetent controls. The median antibody concentrations five years after PCV7 were lower for six pneumococcal serotypes in patients with CLL compared to controls, but the difference was not statistically significant. Depending on the serotype, the percentage of the CLL patients with antibody levels suggested to provide protection against invasive pneumococcal disease (IPD) varied from 29 to 71% five years after vaccination. This data suggests that PCV could result in antibody persistence at least five years in CLL patients.

Background: Infections greatly influence the outcome of acute myeloid leukemia (AML) patients receiving intensive treatment. The aim of this study was to establish the incidence, microbial etiology, risk factors and prognosis of bloodstream infections (BSIs) in patients with AML and compare the results with the previous treatment protocol (AML-92)., Methods: Registery data were gathered prospectively from 357 patients aged 16-65 years recruited on the AML-2003 treatment protocol between November 2003 and November 2011 during different treatment cycles., Results: Blood culture data were available on 977 treatment episodes, in which there were 503 BSIs (51%). The overall incidence rate (IR) for BSIs (per 1000 hospital days) was 16.7. Twenty patients (5.6%) died due to an infection and 16 of them (80%) had a BSI. The most commonly detected microbes (polymicrobial episodes included) in blood cultures were coagulase-negative staphylococci (CoNS, 24.7%), viridans group streptococci (VGS, 19.1%), enterococci (13.9%) and Enterobacteriacae group (25.9%). The etiology of BSIs varied greatly from treatment cycle to cycle., Conclusions: Enterococcal BSIs have increased compared to our previous treatment protocol, and they represent significant pathogens in blood cultures. Infection-related mortality has decreased despite the increase in the IR of BSIs. Enterococci seem to be an increasingly prominent pathogen underlying BSIs in the AML patients, especially during induction therapy (20%).

Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome., (Copyright© Ferrata Storti Foundation.)

The baseline national invasive pneumococcal disease (IPD) incidence rate, serotype distribution and serotype coverage of pneumococcal vaccines were evaluated in patients with Hodgkin's and non-Hodgkin's lymphomas, myeloma and leukaemia within 1 year after haematological diagnosis during 1995-2002, before introduction of pneumococcal conjugate vaccines. Pneumococcal serotype distribution among these patients was different from serotypes causing IPD in the general population. The serotype coverages of PCV13 and PPSV23 were 57% and 64%, respectively, lower than in the general population. This reflects a higher predisposition to IPD in vaccinated patients with haematological malignancies and possibly less benefit of herd immunity gained with the wide use of pneumococcal conjugate vaccines in the general population. This data will be useful as a baseline for determining the future role of adult PCV vaccination in these patient groups.