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Abstract We analyzed the neutrophil-to-lymphocyte ratio (NLR) in 1508 patients with PV and found that those with an NLR ≥ 5 were generally older, had a longer disease history, and had higher cardiovascular risk factors, more arterial thrombosis, and more aggressive blood counts, indicating a more proliferative disease. NLR was an accurate predictor of mortality, with patients with NLR ≥ 5 having significantly worse overall survival and more than twice the mortality rate compared to those with NLR

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Bilateral robotic rehabilitation has proven helpful in the recovery of upper limb motor function in patients with stroke, but its effects on the cortical reorganization mechanisms underlying recovery are still unclear. This pilot Randomized Controlled Trial (RCT) aimed to evaluate the effects on the interhemispheric balance of unilateral or bilateral robotic treatments in patients with subacute stroke, using Quantitative Electroencephalography (qEEG). 19 patients with ischemic stroke underwent a 30-session upper limb neurorehabilitation intervention using a bilateral upper limb exoskeleton. Each patient was randomly assigned to the bilateral (BG, n=10) or unilateral treatment group (UG, n=9). EEG evaluations were performed before (T0) and right after (T $0+\text {)}$ the first treatment session, after 30 treatment sessions (T1), and at 1-week follow-up (T2), in both eyes open and eyes closed conditions. From the acquired EEG data, the pairwise-derived Brain Symmetry Index (pdBSI) was computed. In addition, clinical evaluation was performed at T0 and T1 with validated clinical scales. After the treatment, a significant improvement in clinical and EEG evaluations was observed for both groups, but only the BG showed reduced pdBSI in delta and theta bands. In the cluster of sensorimotor channels, there was no significant difference between groups. The observed changes were not maintained at follow-up. No significant changes were observed in the pdBSI after a single rehabilitation session. Results suggest that balancing of interhemispheric symmetry comes along with a clinical improvement in the upper extremity and that the pdBSI can be used to investigate the mechanisms of neuronal plasticity involved in robotic rehabilitation after stroke.

Abstract We describe 1000 patients with essential thrombocythemia seen at the Center Research and Innovation of Myeloproliferative Neoplasms (CRIMM), Florence, Italy, between 1980 and 2023: median age 59 years (18–95), females 65%, JAK2/CALR/MPL-mutated 66%/19%/4%, triple-negative (TN) 11%. Extreme thrombocytosis (ExT, platelets ≥1000 × 109/L) in 16%, leukocytosis (leukocytes >11 × 109/L) in 16%, and at least one cardiovascular risk factor in 52% of cases. JAK2-mutated patients were older (median 62 years) and CALR-mutated and TN (53 years for both) younger (p

Not available.

Abstract Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%–20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and ‐in primary MF‐ also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF. Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p‐y). This rate reached respectively 4.3% and 4.5% p‐y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p‐y and it reached 4.86% p‐y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion‐dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p‐y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.

Abstract Background Incorporating real‐world data in the drug development process allows the improvement of health outcomes by providing better representation of actual patterns of drug safety and efficacy. Aims and Methods Here, we present the results of a retroprospective, observational real‐life study of 154 patients with myelofibrosis treated with ruxolitinib in a real‐life setting in seven Italian centers of the MYNERVA project. Results Median drug exposure was 29 (range, 3–98) months. Discontinuation rate was 27% after a median time of 13 (range, 3–61). While hematological toxicities were in line with previous findings, infections occurred frequently, representing a not negligible cause of discontinuation and death. Anemia, symptoms, and spleen responses were obtained at any time in 23%, 91%, and 68% of patients, respectively; most patients achieved their responses by week 24. Larger splenomegaly and delayed treatment initiation correlated with lower spleen response at 24 weeks. Spleen response was associated with a superior overall survival, regardless of DIPSS. Of interest, both achievement and loss of spleen response had prognostic implications. Discussion and Conclusion Overall, our findings provide insights on the efficacy and safety of ruxolitinib in a real‐world, multicenter cohort of Italian MF patients.

In systemic mastocytosis, cytoreductive treatment is indicated for advanced systemic mastocytosis (AdvSM) variants. The treatment scenario is rapidly diversifying especially with the introduction of KIT tyrosine kinase inhibitors. Avapritinib is a second-generation potent and selective inhibitor of the mutant KIT D816V that, based on the results of pivotal clinical trials, was approved for the treatment of adults with AdvSM by the regulatory agencies US FDA and EMA. The present article reports the experience of treating SM patients with avapritinib in an Italian compassionate use program. The data from our case series confirm the drug as being active after multiple lines of treatment allowing rapid achievement of profound responses, making it also an effective bridging strategy to allogeneic transplant in eligible patients. However, the anticipated wider use of avapritinib in the near future will require careful monitoring of side effects, especially in heavily pretreated patients.

Measurable residual disease (MRD) is a powerful predictor of outcome in acute myeloid leukemia. In the early phases of treatment, MRD refines initial disease risk stratification and is used for the allocation to allogeneic transplant. Despite its well-established role, a relatively high fraction of patients eventually relapses albeit achieving MRDneg status. The aim of this work was to assess specifically the influence of baseline features and treatment intensity on the predictive value of an MRDneg status, particularly focusing on MRD2, measured after two consecutive chemotherapy cycles. Among baseline features, younger MRD2neg patients (

The development and approval of ruxolitinib, the first JAK1/2 inhibitor indicated to treat myelofibrosis, has improved patient outcomes, with higher spleen and symptoms responses, improved quality of life, and overall survival. Despite this, several unmet needs remain, including the absence of resistance criteria, suboptimal response, the timing of allogeneic transplant, and the management of patients in case of intolerance. Here, we report the results of the second survey led by the “MPN Lab” collaboration, which aimed to report physicians’ perspectives on these topics. As in our first survey, physicians were selected throughout Italy, and we included those with extensive experience in treating myeloproliferative neoplasms and those with less experience representing clinical practice in the real world. The results presented here, summarized using descriptive analyses, highlight the need for a clear definition of response to ruxolitinib as well as recommendations to guide the management of ruxolitinib under specific conditions including anemia, thrombocytopenia, infections, and non-melanoma skin cancers.

Abstract We investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictor of thrombosis in polycythemia vera (PV). After a median follow-up of 2.51 years, of 1508 PV patients enrolled in the ECLAP study, 82 and 84 developed arterial and venous thrombosis, respectively. Absolute counts of total leukocytes, neutrophils, lymphocytes, platelets, and the NLR were tested by generalized additive models (GAM) to evaluate their trend in continuous scale of thrombotic risk. Only for venous thrombosis, we showed that baseline absolute neutrophil and lymphocyte counts were on average respectively higher (median: 6.8 × 109/L, p = 0.002) and lower (median: 1.4 × 109/L, p = 0.001), leading to increased NLR values (median: 5.1, p = 0.002). In multivariate analysis, the risk of venous thrombosis was independently associated with previous venous events (HR = 5.48, p ≤ 0.001) and NLR values ≥5 (HR = 2.13, p = 0.001). Moreover, the relative risk in both low- and high-standard risk groups was almost doubled in the presence of NLR ≥ 5. These findings were validated in two Italian independent external cohorts (Florence, n = 282 and Rome, n = 175) of contemporary PV patients. Our data support recent experimental work that venous thrombosis is controlled by innate immune cells and highlight that NLR is an inexpensive and easily accessible prognostic biomarker of venous thrombosis.

Abstract Background In the field of myoelectric control systems, pattern recognition (PR) algorithms have become always more interesting for predicting complex electromyography patterns involving movements with more than 2 Degrees of Freedom (DoFs). The majority of classification strategies, used for the prosthetic control, are based on single, hierarchical and parallel linear discriminant analysis (LDA) classifiers able to discriminate up to 19 wrist/hand gestures (in the 3-DoFs case), considering both combined and discrete motions. However, these strategies were introduced to simultaneously classify only 2 DoFs and their use is limited by the lack of online performance measures. This study introduces a novel classification strategy based on the Logistic Regression (LR) algorithm with regularization parameter to provide simultaneous classification of 3 DoFs motion classes. Methods The parallel PR-based strategy was tested on 15 healthy subjects, by using only six surface EMG sensors. Twenty-seven discrete and complex elbow, hand and wrist motions were classified by keeping the number of electromyographic (EMG) electrodes to a bare minimum and the classification error rate under 10 %. To this purpose, the parallel classification strategy was implemented by using three classifiers one for each DoF: the “Elbow classifier”, the “Wrist classifier”, and the “Hand classifier” provided the simultaneous control of the elbow, hand, and wrist joints, respectively. Results Both the offline and real-time performance metrics were evaluated and compared with the LDA parallel classification results. The real-time recognition results were statistically better with the LR classifier with respect to the LDA classifier, for all motion classes (elbow, hand and wrist). Conclusions In this paper, a novel parallel PR-based strategy was proposed for classifying up to 3 DoFs: three joint classifiers were employed simultaneously for classifying 27 motion classes related to the elbow, wrist, and hand and promising results were obtained.

Abstract Arterial (AT) and venous (VT) thrombotic events are the most common complications in patients with polycythemia vera (PV) and are the leading causes of morbidity and mortality. In this regard, the impact of JAK2V617F variant allele frequency (VAF) is still debated. The purpose of the current study was to analyze the impact of JAK2V617F VAF in the context of other established risk factors for thrombosis in a total of 865 2016 WHO-defined PV patients utilizing two independent cohorts: University of Florence (n = 576) as a training cohort and Policlinico Gemelli, Catholic University, Rome (n = 289) as a validation cohort. In the training cohort VT free-survival was significantly shorter in the presence of a JAK2V617F VAF > 50% (HR 4; p 50% (HR 3.8, p = 0.001) and previous VT (HR 2.2; p = 0.04) as independent risk factors for future VT whereas diabetes (HR 2.4; p = 0.02), hyperlipidemia (HR 2.3; p = 0.01) and previous AT (HR 2; p = 0.04) were independent risk factors for future AT. Similarly, JAK2V617F VAF > 50% (HR 2.4; p = 0.01) and previous VT (HR 2.8; p = 0.005) were confirmed as independent predictors of future VT in the validation cohort. Impact of JAK2V617F VAF > 50% on VT was particularly significant in conventional low-risk patients, both in Florence (HR 10.6, p = 0.005) and Rome cohort (HR 4; p = 0.02). In conclusion, we identified JAK2V617F VAF > 50% as an independent strong predictor of VT, supporting that AT and VT are different entities which might require distinct management.

Abstract Eosinophilia represents a group of diseases with heterogeneous pathobiology and clinical phenotypes. Among the alterations found in primary Eosinophilia, gene fusions involving PDGFRα, PDGFRβ, FGFR1 or JAK2 represent the biomarkers of WHO-defined “myeloid and lymphoid neoplasms with eosinophilia”. The heterogeneous nature of genomic aberrations and the promiscuity of fusion partners, may limit the diagnostic accuracy of current cytogenetics approaches. To address such technical challenges, we exploited a nanopore-based sequencing assay to screen patients with primary Eosinophilia. The comprehensive sequencing approach described here enables the identification of genomic fusion in 60 h, starting from DNA purified from whole blood.

INTRODUCTION: Platypnea-orthodeoxia syndrome (POS) is a rare syndrome characterized by dyspnea and arterial oxyhemoglobin desaturation induced by moving to the upright position and relieved by recumbency. Different pathogenic processes can lead to POS including cardiopulmonary and hepatopulmonary disorders. CASE PRESENTATION: We here present an unusual case of POS triggered by a previous severe SARSCoV-2 pneumonia in a 66-year-old man admitted to our Emergency Department with worsening dyspnea and chest pain. CONCLUSIONS: SARS-CoV-2 pneumonia should be considered an emerging cause of POS because of its pulmonary and cardiac/intravascular pathological implications.

The COVID-19 sequelae have been shown to affect respiratory and cardiological functions as well as neuro-psychological functions, and, in some cases, metabolic/nutritional aspects. The Italian National Institute for Insurance against Accidents at Work (Istituto Nazionale Assicurazione Infortuni sul Lavoro, INAIL) recorded that, until December 2022, 315,055 workers were affected by COVID-19; therefore, there is a need to identify an effective approach to treat such patients. Robotic and technological devices could be integrated into the rehabilitation programme of people with long COVID conditions. A review of the literature showed that telerehabilitation may improve functional capacity, dyspnoea, performance, and quality of life in these patients, but no studies were found evaluating the effects of robot-mediated therapy or virtual reality systems. Considering the above, Fondazione Don Carlo Gnocchi and INAIL propose a multi-axial rehabilitation for workers with COVID-19 sequelae. To accomplish this goal, the two institutions merged the epidemiological information gathered by INAIL, the expertise in robotic and technological rehabilitation of Fondazione Don Carlo Gnocchi, and the literature review. Our proposal aims to facilitate a multi-axial rehabilitation approach customized to meet the unique needs of each individual, with a particular emphasis on utilizing advanced technologies to address the current and future challenges of patient care.

Abstract In a multicenter European retrospective study including 162 patients with COVID-19 occurring in essential thrombocythemia (ET, n = 48), polycythemia vera (PV, n = 42), myelofibrosis (MF, n = 56), and prefibrotic myelofibrosis (pre-PMF, n = 16), 15 major thromboses (3 arterial and 12 venous) were registered in 14 patients, of whom all, but one, were receiving LMW-heparin prophylaxis. After adjustment for the competing risk of death, the cumulative incidence of arterial and venous thromboembolic events (VTE) reached 8.5% after 60 days follow-up. Of note, 8 of 12 VTE were seen in ET. Interestingly, at COVID-19 diagnosis, MPN patients had significantly lower platelet count (p

Indolent, non-progressive choroidal alterations can be strongly suggestive of neurofibromatosis type 1 (NF1) but are also rarely of unknown aetiology. A 63-year-old man presented for a routine examination. Comprehensive ophthalmological examination and retinal imaging was performed. Visual acuity was 20/20. The anterior segment and fundus were unremarkable. Near-infrared reflectance (NIR) with spectral-domain optical coherence tomography showed unilateral hyperreflective areas in the left posterior pole, corresponding to choroidal nodules on enhanced depth imaging and hypofluorescent areas on indocyanine green angiography. Dermatological evaluation and genetic testing for NF1 were negative. Chest computed tomography, liver function, HLA-A29, and angiotensin-converting enzyme level were negative. The patient has remained in good health and the choroidal alterations have remained non-progressive for 3 years. Choroidal alterations observed with NIR could be a manifestation of somatic mosaicism or a variation of a new unclassified correlated condition that may be better elucidated in the future, given the use of novel imaging techniques that are currently available in ophthalmology.