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This article discusses the impact of annual case volume on the outcomes and safety of colorectal endoscopic submucosal dissection (ESD) procedures. The study included 3770 colorectal ESDs performed in 13 participating centers. The results showed that high-volume centers had higher rates of en bloc resection, R0 resection, and curative resection compared to middle-volume and low-volume centers. The duration of the procedure was also shorter in high-volume centers. However, the study found that the volume of the center was not a significant risk factor for complications such as perforation. Overall, the study suggests that colorectal ESD can be successfully implemented in non-expert settings, but challenging cases should still be referred to experts. [Extracted from the article]

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

OBJECTIVES:. Neurologic outcomes of patients under venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be worsened by secondary insults of systemic origin. We aimed to assess whether sepsis, commonly observed during ECMO support, is associated with brain injury and outcomes. DESIGN:. Single-center cohort study of the “exposed-non-exposed” type on consecutive adult patients treated by VA-ECMO. SETTING:. Medical ICU of a university hospital, France, 2013–2020. PATIENTS:. Patients with sepsis at the time of VA-ECMO cannulation (“sepsis” group) were compared with patients without sepsis (“no sepsis” group). The primary outcome measure was poor functional outcome at 90 days, defined by a score greater than or equal to 4 on the modified Rankin scale (mRS), indicating severe disability or death. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. A total of 196 patients were included (“sepsis,” n = 128; “no sepsis,” n = 68), of whom 87 (44.4%) had presented cardiac arrest before VA-ECMO cannulation. A poor functional outcome (mRS ≥ 4) was observed in 99 of 128 patients (77.3%) of the “sepsis” group and 46 of 68 patients (67.6%) of the “no sepsis” group (adjusted logistic regression odds ratio (OR) 1.21, 95% CI, 0.58–2.47; inverse probability of treatment weighting (IPTW) OR 1.24; 95% CI, 0.79–1.95). Subsequent analyses performed according to pre-ECMO cardiac arrest status suggested that sepsis was independently associated with poorer functional outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest (adjusted logistic regression OR 3.44; 95% CI, 1.06–11.40; IPTW OR 3.52; 95% CI, 1.68–7.73), whereas no such association was observed in patients without pre-ECMO cardiac arrest (adjusted logistic regression OR 0.69; 95% CI, 0.27–1.69; IPTW OR 0.76; 95% CI, 0.42–1.35). Compared with the “no sepsis” group, “sepsis” patients presented a significant increase in S100 calcium-binding protein beta concentrations at day 1 (0.94 μg/L vs. 0.52 μg/L, p = 0.03), and more frequent EEG alterations (i.e., severe slowing, discontinuous background, and a lower prevalence of sleep patterns), suggesting brain injury. CONCLUSION:. We observed a detrimental role of sepsis on neurologic outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest, but not in other patients.

The defect in a newborn with abnormal pyruvate dehydrogenase activity was localized to the X component. Pyruvate dehydrogenase (PDH) is an enzyme complex that is part of the metabolic pathway that extracts energy from carbohydrates. It is composed of three enzymes and a large protein called component X. Component X is believed to form a structure that holds the enzymes in proper orientation. The most common defect is found in enzyme 1. Shortly after birth, the baby developed severe metabolic problems. PDH deficiency was suspected and the baby was placed on a special diet. Enzymatic and genetic analyses of cultured cells found that enzymatic activity was 15% of normal and that the missing component in the complex was the X component. Genetic analysis showed that the gene for enzyme 1 was normal. The mother and father made normal amounts of component X, which suggests a new genetic mutation in the child., Studies of human pyruvate dehydrogenase (PDH) deficiency have shown that defects in the [E.sub.1] component are not common, with only a small number of defects associated specifically with the [E.sub.3], [...]

Abstract Background Anti-Jo-1 autoantibodies represent essential markers in the diagnosis of antisynthetase syndrome (ASS). In this retrospective study, we aimed to investigate whether their concentrations and fluctuations could both respectively reflect the severity and evolution of ASS. Methods Between 2015 and 2020, clinical and biological features of ASS patients with at least one positive measure of anti-Jo-1 autoantibody were collected. At each serum sampling, we assessed myositis activity by using the Myositis Intention to Treat Activities Index (MITAX) and compared anti-Jo-1 concentrations with ASS severity, anti-Jo-1 concentrations between patients with and without active disease, and changes in anti-Jo-1 concentrations with disease activity. Results Forty-eight patients with ASS had at least one positive determination of anti-Jo-1 concentration. Among them, twenty-nine patients had at least two determinations of anti-Jo-1 autoantibody in their follow-up. We showed that these autoantibody concentrations were significantly correlated with MITAX (r = 0.4, p = 0.03) and creatine kinase concentration (r = 0.34, p = 0.002) and that they were significantly higher in patients with active disease than in those with inactive disease (91.7 IU/L vs 44.4 IU/L, p = 0.016). During follow-up, we found a significant correlation between fluctuations of anti-Jo-1 autoantibody concentrations and MITAX score (r = 0.7, p

Abstract Background and Aim The prevalence and the role of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) remain unclear, as the literature provides heterogeneous information on the subject. The aim of this study was to determine the prevalence of SIBO in IBS and to assess the correlation between methane and hydrogen levels measured during breath tests and the severity of IBS. Method Two‐hundred and forty‐seven patients with IBS were prospectively included. A glucose breath test (GBT) measured H2 and CH4 production to diagnose SIBO. A test was positive when H2 values exceeded 12 ppm in the first 90 min and/or when a CH4 value exceeded 10 ppm at any time. IBS severity (IBS‐SSS), quality of life (GIQLI), and anxiety and depression (HAD) were assessed to investigate the correlation with H2 and CH4 production. Results The prevalence of SIBO in IBS was 36.4% (9.7% with H2, 26.7% with CH4). CH4 levels were significantly higher in the predominantly constipated patients (P = 0.00), while H2 levels were significantly higher within the diarrheal phenotype (P = 0.01). IBS severity was not correlated with either H2 levels (r = 0.02; P = 0.84) or CH4 levels (r = 0.05; P = 0.64). H2 production was inversely correlated with the quality of life (r = −0.24; P = 0.03) and significantly correlated with the HAD scale (r = 0.22; P = 0.03). The pain and discomfort experienced during GBT was not correlated with methane levels (r = −0.09, P = 0.40), hydrogen levels (r = −0.01, P = 0.93), or sum of both (r = 0.06, P = 0.58), but significantly associated with IBS severity (r = 0.50, P

Abstract Background Electroencephalography (EEG) is recommended for the practical approach to the diagnosis and prognosis of encephalitis. We aimed to investigate the prognostic value of standard EEG (stdEEG) in adult patients with severe herpes simplex encephalitis. Methods We performed a retrospective analysis of consecutive ICU patients with severe herpes simplex encephalitis in 38 French centers between 2006 and 2016. Patients with at least one stdEEG study performed at ICU admission were included. stdEEG findings were reviewed independently by two investigators. The association between stdEEG findings (i.e., background activity, lateralized periodic discharges, seizures/status epilepticus, and reactivity to painful/auditory stimuli) and poor functional outcome, defined by a score on the modified Rankin Scale (mRS) of 3 to 6 (moderate to severe disability or death) at 90 days, were investigated. Results We included 214 patients with at least one available stdEEG study. The first stdEEG was performed after a median time of one (interquartile range (IQR) 0 to 2) day from ICU admission. At the time of recording, 138 (64.5%) patients were under invasive mechanical ventilation. Lateralized periodic discharges were recorded in 91 (42.5%) patients, seizures in 21 (9.8%) and status epilepticus in 16 (7.5%). In the whole population, reactivity to auditory/noxious stimuli was tested in 140/214 (65.4%) patients and was absent in 71/140 (33.2%) cases. In mechanically ventilated patients, stdEEG reactivity was tested in 91/138 (65.9%) subjects, and was absent in 53/91 (58.2%) cases. Absence of reactivity was the only independent stdEEG finding associated with poor functional outcome in the whole population (OR 2.80, 95% CI 1.19 to 6.58) and in the subgroup of mechanically ventilated patients (OR 4.99, 95% CI 1.6 to 15.59). Adjusted analyses for common clinical predictors of outcome and sedation at time of stdEEG revealed similar findings in the whole population (OR 2.03, 95% CI 1.18 to 3.49) and in mechanically ventilated patients (OR 2.62, 95% CI 1.25 to 5.50). Conclusions Absence of EEG reactivity to auditory/noxious stimuli is an independent marker of poor functional outcome in severe herpes simplex encephalitis.

Introduction: The application of single-cell RNA sequencing has greatly improved our understanding of various cellular and molecular mechanisms involved in physiological and pathophysiological processes. However, obtaining living cells for this technique can be difficult under certain conditions. To solve this problem, the methanol fixation method appeared as a promising alternative for routine clinical use. Materials and Methods: In this study, we selected two AML samples that had been fixed in methanol for 12–18 months. Once the cells were rehydrated, these samples were subjected to single-cell RNA sequencing. We then compared the results obtained from these samples with those obtained from the same samples cryopreserved in DMSO. Results: We used a previously validated methanol fixation protocol to perform scRNA-seq on DMSO cryopreserved cells and cells fixed in methanol for more than one year. Preliminary results show that methanol fixation induces some genetic and transcriptional modification compared with DMSO cryopreservation but remains a valuable method for single-cell analysis of primary human leukemia cells. Conclusions: The initial findings from this study highlight certain resemblances in methanol fixation over a 12-month period and cryopreservation with DMSO, along with associated transcriptional level modifications. However, we observed genetic degradation in the fixation condition when extending beyond one year. Despite certain study limitations, it is evident that short-term methanol fixation can be effectively used for leukemia blast samples. Its ease of implementation holds the potential to simplify the integration of this technique into routine clinical practice.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100 mg/m2, instead of the usual dose of 3500 mg/m2, and daily hemodialysis started 24 h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment.We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100 mg/m2 as a viable therapeutic modality in ESRD patients. Resumen: La quimioinmunoterapia basada en una dosis elevada de metotrexato (HD-MTX) es una parte central del enfoque terapéutico estándar del linfoma primario del sistema nervioso central (PCNSL). La insuficiencia renal causa la demora de la eliminación completa de MTX, así como la concentración crítica del mismo. A pesar de las recomendaciones, el estatus de hemodiálisis no debería excluir la HD-MTX.Reportamos el caso de una mujer de 64 años con PCNSL y tratamiento de hemodiálisis crónica que fue exitosamente tratada con quimioinmunoterapia basada en HD-MTX con una dosis ajustada de 100 mg/m2, en lugar de la dosis habitual de 3.500 mg/m2, iniciándose la hemodiálisis diaria al cabo de 24 h. La paciente no reflejó toxicidad significativa y experimentó remisión completa al cabo de un año desde la finalización del tratamiento.Nosotros argumentamos que la enfermedad renal en etapa terminal (ESRD) no constituye un escollo en absoluto para utilizar la HD-MTX para neoplasias hematológicas. Los expertos deberían considerar el uso de una dosis ajustada a 100 mg/m2 como modalidad terapéutica viable en los pacientes de ESRD.

OBJECTIVES:. Electroencephalography (EEG) is one of the main tools for diagnosis and prognostication of encephalopathy. Our two objectives were to assess: 1) the reliability of intensivists’ interpretations (one trained intensivist and nonexpert intensivists) on specific EEG patterns and 2) the feasibility of performing simplified EEG by a trained intensivist in ICU. DESIGN:. Prospective, single-center study. SETTING:. One French tertiary-care center. PATIENTS:. Thirty-six consecutive ICU patients with encephalopathy. INTERVENTION:. A trained intensivist (1-year specific electrophysiologic course) recorded and interpreted EEGs using a 10 monopod montage at bedside. Then, 22 nonexpert intensivists underwent a 1-hour educational session on interpretation of EEG background (activity, continuity, and reactivity) and common patterns seen in ICU. Trained and nonexpert intensivists’ interpretation of EEG recordings was evaluated and compared with an expert neurophysiologist’s interpretation (gold standard). The agreement between the two interpretations was evaluated. Second, the duration of the entire EEG procedure (specifically EEG installation) at bedside was recorded. MEASUREMENTS AND MAIN RESULTS:. Agreements and reliability between the trained intensivist and the neurophysiologist were acceptable for minimal (agreement, 94%; Pearson coefficient, 0.60) and maximal (89%, 0.89) background frequency, burst suppression (agreement, 100%; Kappa coefficient, 1), background continuity (83%, 0.59), and reactivity to auditory stimulus (78%, 0.44). Agreements between the 22 nonexpert intensivists and the neurophysiologist were heterogeneous. As a result, 87% of the 22 nonexpert intensivists obtained an acceptable reliability for the minimum background frequency, 95% for the maximum background frequency, and 73% and 95% for burst suppression and isoelectric background identification, respectively. The median duration of the entire EEG procedure was 47 minutes (43–53 min), including 22 minutes (20–28 min) of EEG installation. CONCLUSIONS:. Intensivists can rapidly learn background activity and identify burst-suppression and isoelectric background. However, more educational sessions are required for interpretation of other EEG patterns frequently observed in the ICU setting.

Background: Gastric per oral endoscopic esophageal myotomy (G-POEM) is a promising procedure to treat refractory gastroparesis. The safety profile of G-POEM is an important topic because gastroparesis is a functional pathology, with a procedure whose effectiveness is between 50 and 65% depending on the studies. Objectives: We present this retrospective multicenter study, with the aim of establishing a safety profile, focusing on serious adverse events (AEs). Design: This was a multicenter observational cohort study conducted in five French expert centers. Methods: All patients who underwent G-POEM for refractory gastroparesis between 2015 and 2021 were included for analysis. AEs were classified into per endoscopic, early postoperative, and late postoperative, up to 1 month. Their severity was assessed using Dindo–Clavien and American Society for Gastrointestinal Endoscopy classification. The primary objective was to evaluate the rate of G-POEM severe AEs. Secondary objectives were to document other postoperative AEs, and to identify predictive factors. Results: In all, 217 patients were included: 81 men and 136 women, mean age 52 ± 17 years. The average procedural time was 44 ± 14 min (12–78). The average hospital stay was 3.7 ± 2.3 days. The AEs rate classified as Clavien–Dindo ⩾3 was 0.4% (one delayed bleeding requiring blood transfusion and endoscopic management). There were no deaths or patients admitted to intensive care unit. The rates of mucosotomy and capnoperitoneum were 3.7 and 1.8%, respectively, without clinical consequences. Most patients (81.5%) did not experience any AE. Three cases of dumping syndrome occurred, quickly managed by dietary measures. Conclusion: Our study confirms the safety of G-POEM with less than 0.5% of serious AEs, medically managed. This outcome makes this a procedure to have a good benefit–risk ratio.

Summary: Background: In malaria-endemic areas, subjects from specific groups like Fulani have a peculiar protection against malaria, with high levels of IgM but also frequent anaemia and splenomegaly. The mechanisms underlying this phenotype remain elusive. Methods: In a cohort study set up in Benin, West Africa, after a careful evaluation of malaria-related phenotypes, we measured the deformability of circulating erythrocytes in genetically distinct groups (including Fulani) living in sympatry, using ektacytometry and microsphiltration, a mimic of how the spleen clears rigid erythrocytes. Heritability of erythrocytes deformability was calculated, followed by a genome-wide association study (GWAS) of the same phenotype. Findings: Compared to non-Fulani, Fulani displayed a higher deformability of circulating erythrocytes, pointing to an enhanced clearance of rigid erythrocytes by the spleen. This phenotype was observed in individuals displaying markers of Plasmodium falciparum infection. The heritability of this new trait was high, with a strong multigenic component. Five of the top 10 genes selected by a population structure-adjusted GWAS, expressed in the spleen, are potentially involved in splenic clearance of erythrocytes (CHERP, MB, PALLD, SPARC, PDE10A), through control of vascular tone, collagen synthesis and macrophage activity. Interpretation: In specific ethnic groups, genetically-controlled processes likely enhance the innate retention of infected and uninfected erythrocytes in the spleen, explaining splenomegaly, anaemia, cryptic intrasplenic parasite loads, hyper-IgM, and partial protection against malaria. Beyond malaria-related phenotypes, inherited splenic hyper-filtration of erythrocytes may impact the pathogenesis of other hematologic diseases. Funding: ANR, National Geographic Society, IMEA, IRD, and Région Ile-de-France.

Decades ago, the treatment for acute myeloid leukemia relied on cytarabine and anthracycline. However, advancements in medical research have introduced targeted therapies, initially employing monoclonal antibodies such as ant-CD52 and anti-CD123, and subsequently utilizing specific inhibitors that target molecular mutations like anti-IDH1, IDH2, or FLT3. The challenge lies in determining the role of these therapeutic options, considering the inherent tumor heterogeneity associated with leukemia diagnosis and the clonal drift that this type of tumor can undergo. Targeted drugs necessitate an examination of various therapeutic targets at the individual cell level rather than assessing the entire population. It is crucial to differentiate between the prognostic value and therapeutic potential of a specific molecular target, depending on whether it is found in a terminally differentiated cell with limited proliferative potential or a stem cell with robust capabilities for both proliferation and self-renewal. However, this cell-by-cell analysis is accompanied by several challenges. Firstly, the scientific aspect poses difficulties in comparing different single cell analysis experiments despite efforts to standardize the results through various techniques. Secondly, there are practical obstacles as each individual cell experiment incurs significant financial costs and consumes a substantial amount of time. A viable solution lies in the ability to process multiple samples simultaneously, which is a distinctive feature of the cell hashing technique. In this study, we demonstrate the applicability of the cell hashing technique for analyzing acute myeloid leukemia cells. By comparing it to standard single cell analysis, we establish a strong correlation in various parameters such as quality control, gene expression, and the analysis of leukemic blast markers in patients. Consequently, this technique holds the potential to become an integral part of the biological assessment of acute myeloid leukemia, contributing to the personalized and optimized management of the disease, particularly in the context of employing targeted therapies.

For decades, the diagnosis, prognosis and thus, the treatment of acute myeloblastic leukemias and myelodysplastic neoplasms has been mainly based on morphological aspects, as evidenced by the French-American-British classification. The morphological aspects correspond quite well, in a certain number of particular cases, to particular evolutionary properties, such as acute myelomonoblastic leukemias with eosinophils or acute promyelocytic leukemias. Advances in biology, particularly “classical” cytogenetics (karyotype) and molecular cytogenetics (in situ hybridization), have made it possible to associate certain morphological features with particular molecular abnormalities, such as the pericentric inversion of chromosome 16 and translocation t(15;17) in the two preceding examples. Polymerase chain reaction techniques have made it possible to go further in these analyses by associating these karyotype abnormalities with their molecular causes, CBFbeta fusion with MYH11 and PML-RAR fusion in the previous cases. In these two examples, the molecular abnormality allows us to better define the pathophysiology of leukemia, to adapt certain treatments (all-transretinoic acid, for example), and to follow up the residual disease of strong prognostic value beyond the simple threshold of less than 5% of marrow blasts, signaling the complete remission. However, the new sequencing techniques of the next generation open up broader perspectives by being able to analyze several dozens of molecular abnormalities, improving all levels of management, from diagnosis to prognosis and treatment, even if it means that morphological aspects are increasingly relegated to the background.

Abstract After decades during which the treatment of acute myeloblastic leukemia was limited to variations around a skeleton of cytarabine/anthracycline, targeted therapies appeared. These therapies, first based on monoclonal antibodies, also rely on specific inhibitors of various molecular abnormalities. A significant but modest prognosis improvement has been observed thanks to these new treatments that are limited by a high rate of relapse, due to the intrinsic chemo and immune-resistance of leukemia stem cell, together with the acquisition of these resistances by clonal evolution. Relapses are also influenced by the equilibrium between the pro or anti-tumor signals from the bone marrow stromal microenvironment and immune effectors. What should be the place of the targeted therapeutic options in light of the tumor heterogeneity inherent to leukemia and the clonal drift of which this type of tumor is capable? Novel approaches by single cell analysis and next generation sequencing precisely define clonal heterogeneity and evolution, leading to a personalized and time variable adapted treatment. Indeed, the evolution of leukemia, either spontaneous or under therapy selection pressure, is a very complex phenomenon. The model of linear evolution is to be forgotten because single cell analysis of samples at diagnosis and at relapse show that tumor escape to therapy occurs from ancestral as well as terminal clones. The determination by the single cell technique of the trajectories of the different tumor sub-populations allows the identification of clones that accumulate factors of resistance to chemo/immunotherapy (“pan-resistant clones”), making possible to choose the combinatorial agents most likely to eradicate these cells. In addition, the single cell technique identifies the nature of each cell and can analyze, on the same sample, both the tumor cells and their environment. It is thus possible to evaluate the populations of immune effectors (T-lymphocytes, natural killer cells) for the leukemia stress-induced alteration of their functions. Finally, the single cells techniques are an invaluable tool for evaluation of the measurable residual disease since not only able to quantify but also to determine the most appropriate treatment according to the sensitivity profile to immuno-chemotherapy of remaining leukemic cells.

Abstract Background EEG-based prognostication studies in intensive care units often rely on a standard 21-electrode montage (stdEEG) requiring substantial human, technical, and financial resources. We here evaluate whether a simplified 4-frontal electrode montage (4-frontEEG) can detect EEG patterns associated with poor outcomes in adult patients under veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods We conducted a reanalysis of EEG data from a prospective cohort on 118 adult patients under VA-ECMO, in whom EEG was performed on admission to intensive care. EEG patterns of interest included background rhythm, discontinuity, reactivity, and the Synek’s score. They were all reassessed by an intensivist on a 4-frontEEG montage, whose analysis was then compared to an expert’s interpretation made on stdEEG recordings. The main outcome measure was the degree of correlation between 4-frontEEG and stdEEG montages to identify EEG patterns of interest. The performance of the Synek scores calculated on 4-frontEEG and stdEEG montage to predict outcomes (i.e., 28-day mortality and 90-day Rankin score $${\ge {4}}$$ ≥ 4 ) was investigated in a secondary exploratory analysis. Results The detection of EEG patterns using 4-frontEEG was statistically similar to that of stdEEG for background rhythm (Spearman rank test, ρ = 0.66, p

Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell-derived disorders characterized by uncontrolled proliferation of differentiated myeloid cells. Two main groups of MPN, BCR::ABL1-positive (Chronic Myeloid Leukemia) and BCR::ABL1-negative (Polycythemia Vera, Essential Thrombocytosis, Primary Myelofibrosis) are distinguished. For many years, cytomorphologic and histologic features were the only proof of MPN and attempted to distinguish the different entities of the subgroup BCR::ABL1-negative MPN. World Health Organization (WHO) classification of myeloid neoplasms evolves over the years and increasingly considers molecular abnormalities to prove the clonal hematopoiesis. In addition to morphological clues, the detection of JAK2, MPL and CALR mutations are considered driver events belonging to the major diagnostic criteria of BCR::ABL1-negative MPN. This highlights the preponderant place of molecular features in the MPN diagnosis. Moreover, the advent of next-generation sequencing (NGS) allowed the identification of additional somatic mutations involved in clonal hematopoiesis and playing a role in the prognosis of MPN. Nowadays, careful cytomorphology and molecular biology are inseparable and complementary to provide a specific diagnosis and to permit the best follow-up of these diseases.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) include three major subgroups—polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF)—which are characterized by aberrant hematopoietic proliferation with an increased risk of leukemic transformation. Besides the driver mutations, which are JAK2, CALR, and MPL, more than twenty additional mutations have been identified through the use of next-generation sequencing (NGS), which can be involved with pathways that regulate epigenetic modifications, RNA splicing, or DNA repair. The aim of this short review is to highlight the impact of molecular biology on the diagnosis, prognosis, and therapeutic management of patients with PV, ET, and PMF.