Positive impact of molecular analysis on prognostic scores in essential thrombocythemia: a single center prospective cohort experience.
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ABSTRACT:
SUBMITTER: Luque Paz D
PROVIDER: S-EPMC6442979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lack of demonstrable mutations affecting JAK2, CALR, or MPL driver genes within the spectrum of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found in about 10% of patients with essential thrombocythemia (ET) and 5-10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. We evaluated a single-center series of 40 triple-negative ET patients, diagnosed according to the 2017 WHO classification criteria and regularly followed up at the Hematology Unit of our Institution, between January 1983 and January 2019. In all patients, NGS was performed using the Illumina Ampliseq Myeloid Panel; morphological and immunohistochemical features of the bone marrow trephine biopsies were also thoroughly reviewed. Nucleotide variants were detected in 35 out of 40 patients. In detail, 29 subjects harbored one or two variants and six cases showed three or more concomitant nucleotide changes. The most frequent sequence variants involved the TET2 gene (55.0%), followed by KIT (27.5%). Histologically, most of the cases displayed a classical ET morphology. Interestingly, prevalent megakaryocytes morphology was more frequently polymorphic with a mixture of giant megakaryocytes with hyperlobulated nuclei, normal and small sized maturing elements, and naked nuclei. Finally, in five cases a mild degree of reticulin fibrosis (MF-1) was evident together with an increase in the micro-vessel density. By means of NGS we were able to identify nucleotide variants in most cases, thus we suggest that a sizeable proportion of triple-negative ET patients do have a clonal disease. In analogy with driver genes-mutated MPNs, these observations may prevent issues arising concerning triple-negative ET treatment, especially when a cytoreductive therapy may be warranted.
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Project description:We evaluated the incidence, clinical characteristics, and prognostic impact of calreticulin (CALR) mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. In all, 48 ET and 14 PMF patients were enrolled, and the presence of CALR mutations was analyzed by direct sequencing. Patients were classified into three subgroups according to Janus kinase 2 (JAK2) V617F and CALR mutation status, and their clinical features and prognosis were compared. CALR mutations were detected in 15 (24.2%) patients, and the incidence increased to 50.0% in 30 JAK2 V617F mutation-negative cases. These included 11 patients with three known mutations (c.1092_1143del [seven cases], c.1154_1155insTTGTC [three cases], and c.1102_1135del [one case]) and 4 patients with novel mutations. ET patients carrying CALR mutation were younger, had lower white blood cell counts, and experienced less thrombosis during follow-up than those carrying JAK2 V617F mutation, while both patient groups showed similar clinical features and prognosis. In ET patients without JAK2 V617F mutation, CALR mutation did not significantly affect clinical manifestation and prognosis. In conclusion, CALR mutation analysis could be a useful diagnostic tool for ET and PMF in 50% of the cases without JAK2 V617F mutations. The prognostic impact of CALR mutations needs further investigation.
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Project description:Virtually, all studies reporting the outcomes of living kidney donation beyond the first year from donation were retrospective. In this prospective study, the outcome of 81 consecutive living kidney donors was thoroughly evaluated. Clinical, laboratory, and radiological assessments were carried out at predonation (basal), 3, 6, 12, and 24 months after donation. The mean age at time of donation was 37.8 ± 9.8 years and the majority was females (75.3%). The mean BMI increased significantly after donation (P < 0.04). The mean serum creatinine levels (mg/dl) were 0.75 ± 0.14, 1.01 ± 0.22, 0.99 ± 0.21, 0.98 ± 0.20, and 0.94 ± 0.20 (P < 0.0001). Likewise, the mean levels of measured creatinine clearance (mL/min) were 148.8 ± 35.7, 94.7 ± 26.6, 95.5 ± 24.6, 96.7 ± 20.2, and 101.6 ± 26.2 (P < 0.0001). The mean 24 hours urinary protein excretion (gm/dL) were 0.09 ± 0.03, 0.19 ± 0.18, 0.16 ± 0.09, 0.18 ± 0.25, and 0.17 ± 0.12 (P < 0.0001). There were significant increases in the means of the longitudinal and transverse diameters of the remaining kidney over time (P < 0.001). Out of 42 female donors, eleven female donors have got successful postdonation pregnancies. There were no reported surgical complications, either intra- or postoperative. Long-term follow-up is necessary for all living kidney donors through local institutional and world registries. This trial is registered with ClinicalTrials.gov NCT00813579.
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Project description:Limited data is available on long-term outcome predictions for patients with acute-on-chronic liver failure (ACLF) in an intensive care unit (ICU) setting. Assessing the reliability and accuracy of several mortality prediction models for these patients is helpful. Two hundred forty-nine consecutive patients with ACLF and admittance to the liver ICU in a single center in northern Taiwan between December 2012 and March 2015 were enrolled in the study and were tracked until February 2017. Ninety-one patients had chronic hepatitis B-related cirrhosis. Clinical features and laboratory data were collected at or within 24 h of the first ICU admission course. Eight commonly used clinical scores in chronic liver disease were calculated. The primary endpoint was overall survival. Acute physiology and chronic health evaluation (APACHE) III and chronic liver failure consortium (CLIF-C) ACLF scores were significantly superior to other models in predicting overall mortality as determined by time-dependent receiver operating characteristic (ROC) curve analysis (area under the ROC curve (AUROC): 0.817). Subgroup analysis of patients with chronic hepatitis B-related cirrhosis displayed similar results. CLIF-C organ function (OF), CLIF-C ACLF, and APACHE III scores were statistically superior to the mortality probability model III at zero hours (MPM0-III) and the simplified acute physiology (SAP) III scores in predicting 28-day mortality. In conclusion, for 28-day and overall mortality prediction of patients with ACLF admitted to the ICU, APACHE III, CLIF-OF, and CLIF-C ACLF scores might outperform other models. Further prospective study is warranted.
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Project description:BackgroundDonor human milk (DHM) became available in Japan when the first human milk bank was established in 2017. This study investigated the effects of DHM on enteral nutrition (EN) in very low birth weight (VLBW) infants in the single center in Japan.MethodsSeventy-six VLBW infants hospitalized between April 2017 and March 2020 at Showa University Hospital were included in the study. We retrospectively evaluated age (hours) at which EN was initiated and age (days) until complete feeding (EN > 100 mL/kg/day) was achieved. We compared the DHM and non-DHM groups, or the early human milk (EHM) and non-EHM groups. The EHM group was defined as those in which EN was initiated with the mother's own milk or DHM within 12 h of birth.ResultsIn 30 extremely low birth weight (ELBW) infants, EN was initiated at significantly earlier postnatal hours in the DHM group compared to those in the non-DHM group. Complete feeding was achieved at significantly earlier ages in the EHM group after adjusting for gastrointestinal complications and gestational age. Additionally, the changes in body weight z-scores from birth to term-equivalent age were significantly greater in the EHM group after adjusting for exclusive breastfeeding and small for gestational age, compared to the non-EHM group. Statistical significance was not noted in 46 subjects (birth weight, 1000-1500 g).ConclusionThe use of DHM may contribute to earlier initiation and achievement of EN, resulting in greater early postnatal growth in ELBW infants in Japan.
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Project description:We present the case where immune thrombocytopenia (ITP) and essential thrombocythemia (ET) sequentially appeared in the space of twenty-one years of follow-up. Impaired platelet production is present in both diseases, but clinical presentation and treatment are different. On the basis of this case history a possible role of autoimmunity as a predisposing factor to myeloproliferation has been discussed.
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Project description:PurposePreoperative diagnosis of pituicytomas is difficult, and management and prognostic factors remain ambiguous. The purpose of this study was to elucidate the radiological characteristics of pituicytoma, to assess the risk factors affecting tumor progression, and to propose the optimal treatment regimen based on comprehensive analysis.MethodsWe reviewed the clinical data of 22 patients with pituicytoma confirmed pathologically in our institution. In addition, 93 cases of pituicytoma in the previous literature were recruited. The individual data of 115 patients were analyzed to evaluate the adverse factors affecting pituicytoma progression.ResultsIn the combined cohort, 3 of 61 patients who underwent gross-total resection (GTR) developed recurrence (4.9%); of the 54 patients who received non-GTR, 19 progressed (35.2%). Univariate and multivariate Cox regression analysis verified male gender (HR 2.855, 95% CI 1.008-8.089; p = 0.048), TS (transsphenoidal surgery; HR 3.559, 95% CI 1.015-12.476; p = 0.047), and non-GTR (HR 4.388, 95%CI 1.240-15.521; p = 0.022) were independent unfavorable factors for pituicytoma progression. A multivariate logistic regression model verified that tumor diameter ≥ 1.85 cm (OR 4.859, 95% CI 1.335-17.691; p = 0.016) was independent adverse factors for GTR. Compared with TS, OT (open transcranial) is more likely to have postoperative complications (OR 3.185, 95% CI 1.020-9.944; p = 0.046), especially vision deterioration (OR 37.267, 95% CI 4.486-309.595; p = 0.001).ConclusionBased on our findings, GTR was advocated as an optimal treatment for pituicytomas. However, in order to avoid damage to important structures, partial resection is acceptable. After that, adjuvant radiotherapy is recommended for male patients with high Ki-67 index, and the remaining patients can be followed up closely. When the tumor recurs or progresses, it is recommended to re-operate and remove the lesion completely as far as possible. If GTR is still not possible, postoperative radiotherapy for the residual tumor is recommended.
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Project description:ObjectivesIncrease of nucleated RBCs in peripheral blood has been shown to be predictive of mortality in ICU patients. The aim of this study was to explore the prognostic value of nucleated RBCs in the first blood sample taken at admission to the emergency department from patients with suspected sepsis.DesignSingle-center prospective cohort study.SettingEmergency department.PatientsOne-thousand two-hundred thirty-one consecutive adult patients with suspected sepsis were included in a prospective quality register-based cohort study. Inclusion criteria were as follows: patients received in rapid response team with blood cultures taken and immediate antibiotics given in the emergency department.InterventionNot applicable.Measurement and main resultsNucleated RBCs, Sequential Organ Failure Assessment score, Quick Sequential Organ Failure Assessment, Charlson Comorbidity Index, and commonly used laboratory tests measured in the emergency department were compared with 30-day mortality. Nvaucleated RBC counts were divided into five groups, called "Nucleated RBC score," according to nucleated RBC count levels and analyzed with logistic regression together with the Sequential Organ Failure Assessment score and Charlson Comorbidity Index. Of the 262 patients with nucleated RBCs equal to or higher than the detection limit (0.01 × 109/L), 26% died within 30 days, compared with 12% of the 969 patients with nucleated RBCs below the detection limit (p < 0.0001). Mortality was significantly higher for each increase in Nucleated RBC score, except from score 2 to 3, and was 62% in the highest group. In multivariate logistic regression, odds ratios for 30-day mortality were as follows: Nucleated RBC score: 1.33 (95% CI, 1.13-1.56), Sequential Organ Failure Assessment score: 1.32 (1.29-1.56), and Charlson Comorbidity Index: 1.17 (1.09-1.25).ConclusionsMost patients with suspected sepsis in emergency department had undetectable nucleated RBCs at admission to the emergency department. However, increased nucleated RBCs significantly predicted 30-day mortality. Nucleated RBCs may provide additional prognostic information to Sequential Organ Failure Assessment score and other laboratory tests.
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Project description:Iatrogenic tracheal ruptures are rare but severe complications of medical interventions. The main goal of this study was to explore prognostic factors for all-cause mortality and rupture-related (adjusted) mortality. We retrospectively analyzed patients admitted to an academic referral center over a 15-year period (2004-2018). Fifty-four patients met the inclusion criteria, of whom 36 patients underwent surgical repair and 18 patients were treated conservatively. In a 90-day follow-up, the all-cause mortality was 50%, while the adjusted mortality was 13%. Rupture length was identified as a predictor for all-cause mortality (area under the curve, 0.84; 95% confidence interval (CI) 0.74-0.94) with a cutoff rupture length of 4.5 cm (sensitivity, 0.70; specificity, 0.81). Multivariate analysis confirmed rupture length as a prognostic factor for all-cause mortality (adjusted hazard ratio (HR) 1.5; 95% CI 1.2-1.9; p = 0.001), but not for adjusted mortality (HR 1.5; 95% CI 0.97-2.3; p = 0.068), while mediastinitis predicted adjusted mortality (HR 5.8; 95% CI 1.1-31.7; p = 0.042), but not all-cause mortality (HR 1.6; 95% CI 0.7-3.5; p = 0.243). The extent of iatrogenic tracheal rupture and mediastinitis might be relevant prognostic factors for all-cause mortality and adjusted mortality, respectively.
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Project description:In 1934, Epstein and Goedel used the term hemorrhagic thrombocythemia to describe a disorder characterized by permanent elevation of a platelet count to more than three times normal, hyperplasia of megakaryocytes, and the tendency for venous thrombosis and spontaneous hemorrhage. Over the last 75 years, and particularly in the past 6 years, major progress has been made in our understanding of essential thrombocythemia (ET) and its pathogenesis with the identification of the highly prevalent JAK-2 V617F and other mutations. Current management of this condition is based upon historical data and with treatments that have not changed significantly for nearly two decades. This study discusses this and recent progress, highlighting exciting new data with old and new drugs, as well as which patients in particular should be evaluated for these new therapies.
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