Prevention of venous thromboembolism in hematologic neoplasms: an expert consensus from SEHH-SETH.

Venous thromboembolism (VTE) is a serious complication in hematologic neoplasms, so finding adequate prevention strategies is an urgent requirement. However, prospective studies with large enough cohorts are scarce, limiting the development of evidence-based thromboprophylaxis guidelines. The present position paper is addressed to all hematologists treating patients affected by hematologic neoplasms with the aim to provide clinicians with a useful tool for the prevention of VTE.

C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain.

OBJECTIVE: To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. MATERIAL AND METHODS: An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. MEASUREMENTS AND MAIN RESULTS: Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P = 0.0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P < 0.0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P < 0.05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P > 0.05 vs AUC-ROC development). CONCLUSION: Patients COVID-19 presenting at admission SOFA score ≥ 2 combined with CRP ≥ 9.1 mg/mL could be at high risk to require critical care.

C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain. / Proteína C reactiva y escala SOFA: una simple escala como factor predictivo temprano de la necesidad de cuidados críticos en los pacientes con neumonía causada por COVID-19 en España.

OBJECTIVE: To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. MATERIAL AND METHODS: An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. MEASUREMENTS AND MAIN RESULTS: Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P=.0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P<.0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P<.05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P>0.05 vs AUC-ROC development). CONCLUSION: Patients COVID-19 presenting at admission SOFA score ≥2 combined with CRP ≥9,1mg/mL could be at high risk to require critical care.

Risk for post-thrombotic syndrome after lower-limb deep vein thrombosis: location of the thrombus or residual thrombi? / Risk razvitiia posttromboflebiticheskogo sindroma posle tromboza glubokikh ven nizhnikh konechnostei: lokalizatsiia tromba ili rezidual'nyi tromboz?

BACKGROUND: Many works aimed to determine factors that influence the onset of postthrombotic syndrome after an acute episode of deep venous thrombosis. We aimed to compare the prognostic value of the most proximal extent of thrombus (proximal and distal DVT) versus the residual thrombosis as identified by venous ultrasonography performed during follow-up. METHOD: We conducted a retrospective study of prospectively collected 1183 consecutive cohort patients in the RIETE registry after a first episode of deep venous thrombosis and assessed for postthrombotic syndrome after 12 months. RESULTS: Multivariate analysis revealed that: residual thrombosis (OR 1.40; 95% CI 0,88-2,21), the presence of cancer (OR 1.38; 95% CI: 0,64-2,97), immobility (OR 1.31; 95% CI 0,70-2,43) and estrogen-containing drugs use (OR 2.08, 95% CI 0,63-6,83), all had a predictive value for the occurrence of PTS. CONCLUSION: Our study results revealed that ultrasound finding of residual thrombosis is more predictive than proximal location of thrombus for postthrombotic syndrome after episode of deep venous thrombosis. Real life data from a large group of patients from the RIETE registry substantiates that.

[C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain]. / Proteína C reactiva y escala SOFA: una simple escala como factor predictivo temprano de la necesidad de cuidados críticos en los pacientes con neumonía causada por COVID-19 en España.

OBJECTIVE: To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. MATERIAL AND METHODS: An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤ 6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. MEASUREMENTS AND MAIN RESULTS: Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P = .0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P < .0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P < .05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P > 0.05 vs AUC-ROC development). CONCLUSION: Patients COVID-19 presenting at admission SOFA score ≥ 2 combined with CRP ≥ 9,1 mg/mL could be at high risk to require critical care.

Charge Density Waves in YBa_{2}Cu_{3}O_{6.67} Probed by Resonant X-Ray Scattering under Uniaxial Compression.

We report a comprehensive Cu L_{3}-edge resonant x-ray scattering (RXS) study of two- and three-dimensional (2D and 3D) incommensurate charge correlations in single crystals of the underdoped high-temperature superconductor YBa_{2}Cu_{3}O_{6.67} under uniaxial compression up to 1% along the two inequivalent Cu─O─Cu bond directions (a and b) in the CuO_{2} planes. We confirm the strong in-plane anisotropy of the 2D charge correlations and observe their symmetric response to pressure: pressure along a enhances correlations along b, and vice versa. Our results imply that the underlying order parameter is uniaxial. In contrast, 3D long-range charge order is only observed along b in response to compression along a. Spectroscopic RXS measurements show that the 3D charge order resides exclusively in the CuO_{2} planes and may thus be generic to the cuprates. We discuss implications of these results for models of electronic nematicity and for the interplay between charge order and superconductivity.

Experimental data on the relationship between dyes sensitizers and wavelength during the photocatalytic degradation of diclofenac.

Sensitizers are being used to improve the photocatalytic activity of semiconductors in the visible light region of the solar spectrum. Different types of dyes are reported as sensitizer agents, such as ruthenium complex molecules, porphyrins and Pt complexes, which are critically assessed because they are hazardous substance. Therefore, it is necessary to replace these compounds with safer sensitizer like organic dyes. This work evaluated the photocatalytic degradation of diclofenac using two different types of organic dyes (Perinaphtenone and Eosin-Y) as sensitizer agents. The catalyst concentration [0.15; 0.35 g/l], source of light (UVA - Vis) and type of dye were evaluated. The data obtained can be useful to classify organic dyes that could be employees as sensitizers and which is the wavelength more adequate to use as an energy source. The Kapp for the reaction has values between 1*10-3 to 5*10-3 min-1 for UVA, 3*10-4 to 3*10-3 min-1 for Vis and 2*10-3 to 6*10-3 min-1 for UV-Vis.

Uniaxial pressure control of competing orders in a high-temperature superconductor.

Cuprates exhibit antiferromagnetic, charge density wave (CDW), and high-temperature superconducting ground states that can be tuned by means of doping and external magnetic fields. However, disorder generated by these tuning methods complicates the interpretation of such experiments. Here, we report a high-resolution inelastic x-ray scattering study of the high-temperature superconductor YBa2Cu3O6.67 under uniaxial stress, and we show that a three-dimensional long-range-ordered CDW state can be induced through pressure along the a axis, in the absence of magnetic fields. A pronounced softening of an optical phonon mode is associated with the CDW transition. The amplitude of the CDW is suppressed below the superconducting transition temperature, indicating competition with superconductivity. The results provide insights into the normal-state properties of cuprates and illustrate the potential of uniaxial-pressure control of competing orders in quantum materials.

Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia.

Essentials Diagnosis of sitosterolemia, a rare recessive or syndromic disorder, is usually delayed. Peripheral blood smear is extremely useful for establishing the suspicion of sitosterolemia. High-throughput sequencing technology enables the molecular diagnosis of inherited thrombocytopenias. Accurate characterization of sitosterolemia helps us determine appropriate management. SUMMARY: Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.

Optically induced lattice deformations, electronic structure changes, and enhanced superconductivity in YBa2Cu3O6.48.

Resonant optical excitation of apical oxygen vibrational modes in the normal state of underdoped YBa2Cu3O6+x induces a transient state with optical properties similar to those of the equilibrium superconducting state. Amongst these, a divergent imaginary conductivity and a plasma edge are transiently observed in the photo-stimulated state. Femtosecond hard x-ray diffraction experiments have been used in the past to identify the transient crystal structure in this non-equilibrium state. Here, we start from these crystallographic features and theoretically predict the corresponding electronic rearrangements that accompany these structural deformations. Using density functional theory, we predict enhanced hole-doping of the CuO2 planes. The empty chain Cu dy2-z2 orbital is calculated to strongly reduce in energy, which would increase c-axis transport and potentially enhance the interlayer Josephson coupling as observed in the THz-frequency response. From these results, we calculate changes in the soft x-ray absorption spectra at the Cu L-edge. Femtosecond x-ray pulses from a free electron laser are used to probe changes in absorption at two photon energies along this spectrum and provide data consistent with these predictions.

Persistent Paramagnons Deep in the Metallic Phase of Sr_{2-x}La_{x}IrO_{4}.

We have studied the magnetic excitations of electron-doped Sr_{2-x}La_{x}IrO_{4} (0≤x≤0.10) using resonant inelastic x-ray scattering at the Ir L_{3} edge. The long-range magnetic order is rapidly lost with increasing x, but two-dimensional short-range order (SRO) and dispersive magnon excitations with nearly undiminished spectral weight persist well into the metallic part of the phase diagram. The magnons in the SRO phase are heavily damped and exhibit anisotropic softening. Their dispersions are well described by a pseudospin-1/2 Heisenberg model with exchange interactions whose spatial range increases with doping. We also find a doping-independent high-energy magnetic continuum, which is not described by this model. The spin-orbit excitons arising from the pseudospin-3/2 manifold of the Ir ions broaden substantially in the SRO phase, but remain largely separated from the low-energy magnons. Pseudospin-1/2 models are therefore a good starting point for the theoretical description of the low-energy magnetic dynamics of doped iridates.

Real-life management of primary immune thrombocytopenia (ITP) in adult patients and adherence to practice guidelines.

Very few data exist on the management of adult patients diagnosed with primary immune thrombocytopenia (ITP). The objectives of this study were to describe the diagnostic and treatment patterns for ITP and to compare the findings to recent ITP guidelines. We retrospectively analyzed the medical records of adult ITP patients diagnosed with primary ITP between January 2011 and June 2012 and examined whether management strategies were consistent or not with eight recent guideline-recommended practices. Overall, median age at the diagnosis of the disease (n = 101) was 58 years and median platelet count 12 × 10(9)/L with 75.2 % of patients having symptoms of ITP. The study perceived two major shortcomings in the diagnostic approach: (1) failure to perform peripheral blood film examination in 22.8 % of patients, a test that is mandatory by all guidelines, and (2) ordinary bone marrow assessment in more than half of the patients at diagnosis (50.5 %), a test not routinely recommended by guidelines. Low appropriateness in therapeutic management of patients included (1) unjustified use of intravenous immunoglobulin in the absence of bleeding in 54.8 % of patients and (2) splenectomy not being deferred until 6-12 months from diagnosis (median 161 days). Data also reflect a trend towards the early use of thrombopoietin receptor agonists in the treatment of patients who are refractory to any first-line therapy. We have recognized important areas of inapropriateness in the diagnostic and therapeutic management of adult ITP patients. Compliance with established guidelines should be encouraged in order to improve patient outcomes.

Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders.

INTRODUCTION: Molecular testing of Inherited bleeding coagulation disorders (IBCDs) not only offers confirmation of diagnosis but also aids in genetic counselling, prenatal diagnosis and in certain cases genotype-phenotype correlations are important for predicting the clinical course of the disease and to allow tailor-made follow-up of individuals. Until recently, genotyping has been mainly performed by Sanger sequencing, a technique known to be time consuming and expensive. Currently, next-generation sequencing (NGS) offers a new potential approach that enables the simultaneous investigation of multiple genes at manageable cost. AIM: The aim of this study was to design and to analyse the applicability of a 23-gene NGS panel in the molecular diagnosis of patients with IBCDs. METHODS: A custom target enrichment library was designed to capture 31 genes known to be associated with IBCDs. Probes were generated for 296 targets to cover 86.3 kb regions (all exons and flanking regions) of these genes. Twenty patients with an IBCDs phenotype were studied using NGS technology. RESULTS: In all patients, our NGS approach detected causative mutations. Twenty-one pathogenic variants were found; while most of them were missense (18), three deletions were also identified. Six novel mutations affecting F8, FGA, F11, F10 and VWF genes, and 15 previously reported variants were detected. NGS and Sanger sequencing were 100% concordant. CONCLUSION: Our results demonstrate that this approach could be an accurate, reproducible and reliable tool in the rapid genetic diagnosis of IBCDs.

Collective nature of spin excitations in superconducting cuprates probed by resonant inelastic X-ray scattering.

We used resonant inelastic x-ray scattering (RIXS) with and without analysis of the scattered photon polarization, to study dispersive spin excitations in the high temperature superconductor YBa_{2}Cu_{3}O_{6+x} over a wide range of doping levels (0.1≤x≤1). The excitation profiles were carefully monitored as the incident photon energy was detuned from the resonant condition, and the spin excitation energy was found to be independent of detuning for all x. These findings demonstrate that the largest fraction of the spin-flip RIXS profiles in doped cuprates arises from magnetic collective modes, rather than from incoherent particle-hole excitations as recently suggested theoretically [Benjamin et al. Phys. Rev. Lett. 112, 247002 (2014)]. Implications for the theoretical description of the electron system in the cuprates are discussed.

Slow femoral venous flow and venous thromboembolism following inguinal hernioplasty in patients without or with low molecular weight heparin prophylaxis.

BACKGROUND: Prosthetic material (mesh) is commonly used to repair inguinal hernias. Its implantation close to the common femoral vein (CFV) can induce slow flow and favor the appearance of venous thromboembolism (VTE) events. AIM: To investigate the speed of flow, diameter and area of the CFV after inguinal hernioplasty. METHODS: Two hundred and fifty patients receiving open hernioplasty with a non-resorbable mesh for the repair of a unilateral, primary, simple inguinal hernia were prospectively investigated. Patients were stratified, by consensus, into a low or a moderate risk of VTE group. The moderate-risk group (n = 163) received low molecular weight heparin. On day 10 post-operation a blinded Echo-Doppler was carried out, and repeated 7 days later in patients with a venous flow of <15 cm/s. The speed of flow (cm/s), diameter (cm), and area (cm(2)) of the ipsilateral and contralateral CFV of the groin operated upon were measured. RESULTS: No event symptomatic of VTE was documented. One case of asymptomatic deep vein thrombosis (1/163, 0.6%) was found in the moderate-risk group. In 29 patients (2 and 27 in the low- and moderate-risk groups, respectively; p < 0.001) a maximum blood flow velocity of <15 cm/s was found in the ipsilateral CFV; these flows were close to normal in the second measurement. Taking the entire sample into account, the maximum venous blood flow found in the ipsilateral CFV of the operated groin was less than that measured in the contralateral CFV (20.88 vs. 24.01 cm/s; p < 0.001); this difference was significant in both VTE risk groups. The diameter and area of the CFV were both greater in the ipsilateral than the contralateral CFV (p < 0.01); this finding proved to be significant only in hernias of the left groin (p < 0.001). CONCLUSIONS: In the immediate postoperative period, inguinal hernioplasty with mesh induces a temporarily slow venous flow in the ipsilateral CFV. However, this does not lead to an increase in the incidence of VTE.

The role of the TERC-63G>A and TERT-1327C>T telomerase polymorphisms in the study of men with acute coronary syndrome.

AIM: Telomerase is a ribonucleoprotein that maintains telomere length. Telomeres and telomerase are involved in cellular ageing and have been connected to some ageing related diseases, like cardiovascular disease. Telomerase dysfunction could be the main underlying mechanism in this connection but this point is still unclear. The aim of this article is to investigate the possible influence of cellular ageing, measured by two telomerase polymorphisms, TERC-63G>A (rs2293607) and TERT-1327C>T (rs2735940), on the whole spectrum of acute coronary artery disease (CAD). METHODS: We studied 150 middle aged men admitted for an acute coronary syndrome (ACS). Cardiovascular risk factors prevalence was collected at admission. Severity variables analyzed were Killip class and number of vessels affected. Telomerase polymorphisms were studied by real time PCR in DNA samples extracted from peripheral blood leukocytes. Clinical follow-up had been developed for more than 600 days and a prognostic combined event was defined. RESULTS: C allele of TERT polymorphism was more prevalent among hypertensive patients (OR: 3.19; 95% CI: 1.37-7.42; P=0.006). None of polymorphisms showed any prognostic value or relation to CAD severity. CONCLUSION: Telomerase dysfunction could be involved in hypertension prevalence. This finding could support new screening strategies in high risk population. The two telomerase polymorphisms analyzed did not show any prognostic value or connection to CAD severity. However, further studies are required to determine the molecular mechanisms responsible for cellular ageing in ACS.

Relative value of the Ankle-Brachial Index of intermittent claudication.

INTRODUCTION: The Ankle-Brachial Index (ABI) makes it possible to identify patients with peripheral artery disease (PAD). Intermittent claudication (IC) is the first major symptom of PAD, although many patients with an ABI ≤ 0.9 do not exhibit IC, and the range of ABI among those who do have IC is very variable. This study evaluates the correlation between ABI and the perception (symptomatology) of claudicant patients. MATERIAL AND METHODS: An observational, cross-sectional and multicentre, study of 920 patients with IC. Clinical history, ABI, Walking Impairment Questionnaire (WIQ) and European Quality of Life Questionnaire (EQ-5D) were recorded. Associations were analysed using Spearman's correlation coefficient. RESULTS: The mean ABI of the series was 0.63 (SD = 0.19). The mean WIQ-distance was 34.07 (SD = 26.77), values being smaller for lower ABI values (r = 0.343, p < 0.001). The mean EQ-5D score of the series was 0.58 (SD = 0.21), also showing lower values as the ABI decreased (r = 0.278, p < 0.001). The correlations of WIQ and EQ-5D with ABI were statistically significant in both cases, but always less than 0.400 (between 0.278 and 0.343). CONCLUSIONS: The correlations of ABI with the questionnaires of walking capacity and quality of life are weak. For this reason, although in clinical practice the ABI of CI patients is commonly measured, decisions should not be taken during the development of IC exclusively on the basis of the ABI.

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus.

Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.