Atresia of inferior vena cava (IVC) is a rare congenital malformation associated with high risk of venous thrombosis that still has unknown etiology, although intrauterine IVC thrombosis has been ...suggested to be involved. The identification of IVC atresia in a case with early idiopathic venous thrombosis and antithrombin deficiency caused by the homozygous SERPINC1 c.391C > T variant (p.Leu131Phe; antithrombin Budapest 3) encouraged us to evaluate the role of this severe thrombophilia in this vascular abnormality. We have done a cross‐sectional study in previously identified cohorts of patients homozygous for the Budapest 3 variant (N = 61) selected from 1118 patients with congenital antithrombin deficiency identified in two different populations: Spain (N = 692) and Hungary (N = 426). Image analysis included computed tomography and phlebography. Atresia of the IVC system was observed in 17/24 cases (70.8%, 95% confidence interval CI: 48.9%–87.3%) homozygous for antithrombin Budapest 3 with available computed tomography (5/8 and 12/16 in the Spanish and Hungarian cohorts, respectively), 16 had an absence of infrarenal IVC and one had atresia of the left common iliac vein. All cases with vascular defects had compensatory mechanisms, azygos‐hemiazygos continuation or double IVC, and seven also had other congenital anomalies. Short tandem repeat analysis supported the specific association of the IVC system atresia with SERPINC1. We show the first evidence of the association of a severe thrombophilia with IVC system atresia, supporting the possibility that a thrombosis in the developing fetal vessels is the reason for this anomaly. Our hypothesis‐generating results encourage further studies to investigate severe thrombophilic states in patients with atresia of IVC.
While the incidence of thrombotic complications in critically ill patients is very high, in patients under non-invasive respiratory support (NIS) is still unknown. The specific incidence of ...thrombotic events in each of the clinical scenarios within the broad spectrum of severity of COVID-19, is not clearly established, and this has not allowed the implementation of thromboprophylaxis or anticoagulation for routine care in COVID-19. Patients admitted in a semi-critical unit treated initially with NIS, especially Continuous-Positive Airway Pressure (CPAP), were included in the study. The cumulative incidence of pulmonary embolism was analyzed and compared between patients with good response to NIS and patients with clinical deterioration that required orotracheal intubation. 93 patients were included and 16% required mechanical ventilation (MV) after the NIS. The crude cumulative incidence of the PE was 14% (95%, CI 8–22) for all group. In patients that required orotracheal intubation and MV, the cumulative incidence was significantly higher 33% (95%, CI 16–58) compared to patients that continued with non-invasive support 11% (CI 5–18) (Log-Rank, p = 0.013). Patients that required mechanical ventilation were at higher risk of PE for a HR of 4.3 (95%CI 1.2–16). In conclusion, cumulative incidence of PE is remarkably higher in critically patients with a potential impact in COVID-19 evolution. In this context, patients under NIS are a very high-risk group for developing PE without a clear strategy regarding thromboprophylaxis.
•The incidence of pulmonary embolism is higher in critically patients.•C-Reactive Protein is probably the best biomarker to follow-up patients with severe COVID-19.•Pulmonary embolism is frequent in COVID-19 cases with non-invasive respiratory support.
Abstract Introduction NPM1 ‐mutated ( NPM1 mut ) myeloid neoplasms (MNs) with <20% bone marrow (BM) blasts ( NPM1 mut MNs<20) are uncommon, and their classification remains inconsistent. Methods The ...clinicopathologic features of 54 patients with NPM1 mut MNs <20 were evaluated and compared with wild‐type NPM1 MNs <20 and NPM1 mut MNs≥20, respectively. Results NPM1 mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p = .023) and FLT3 (70% vs 11%, p < .001) frequency in patients with ≥20% BM blasts. Thirty‐three (61%) patients with NPM1 mut MNs <20 received low‐intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p = .006) and median overall survival (mOS) (not reached vs 30.4 months, p = .06) were observed with IC compared to LIC. Young patients (age <60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p = .025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for <10%, 10%–19%, and ≥20% blasts, p = .700) regardless of treatment modality (LIC: p = .900; IC: p = .360). Twenty‐three patients (43%) with NPM1 mut MNs <20 had marrow blast progression to ≥20%. Conclusions Overall, NPM1 mut MNs define a unique entity independent of BM blast percentage.
NPM1 mutations define a unique leukemia entity regardless of bone marrow blast percentage. Patients with NPM1‐mutated myeloid neoplasms benefit from intensive chemotherapy approaches even in the setting of low bone marrow blast percentage.
Absorption Equilibria of Dilute SO2 in Seawater Rodríguez-Sevilla, Juan; Álvarez, Manuel; Díaz, María C ...
Journal of chemical and engineering data,
11/2004, Letnik:
49, Številka:
6
Journal Article
Recenzirano
The solubility of dilute SO2 in seawater, from mixtures SO2 + N2, was determined in a temperature range between (278.15 and 318.15) K and a SO2 partial pressure range between (0.050 and 1.5) kPa. ...Measurements were carried out by a saturation method using a laboratory-stirred batch reactor. Equations to correlate experimental data were obtained as a function of temperature and SO2 partial pressure. Comparisons between experimental results, literature data, and theoretical predictions were also made at different temperatures. Two different models were considered to evaluate the activity coefficients of ionic species. Theoretical calculations were made using both an extended version of the Debye−Hückel theory and the Pitzer ion-interaction model. Both models led to similar predictions and were in good agreement with the experimental results. The reasonable fitting between measured and calculated data showed that the selected models can be successfully used for predicting the absorption equilibria of dilute sulfur dioxide in seawater at different temperatures.
The solubility of dilute SO2 in aqueous HCl and NaCl solutions was determined at 298.15 K as a function of ionic strength up to 3 mol·L-1, in the partial pressure range between (0.075 and 1.8) kPa. ...Measurements were carried out by a saturation method using a laboratory batch reactor. Equations to correlate the apparent Henry's law constant, H m, and the apparent first dissociation constant, K m1, were obtained as a function of ionic strength. Comparisons between experimental results and theoretical predictions were also made. A model based on the classical Sechenov equation was tested, and a new value for the SO2 gas-specific parameter was obtained to calculate H m. Two different models were considered for calculating the activity coefficients to determine K m1. An extended version of the Debye−Hückel theory described the experimental results for ionic strengths below 0.1 mol·L-1. The Pitzer model was in good agreement with the experimental data in the ionic strength range between (0 and 3) mol·L-1. The close fit between measured and calculated data showed that the selected models can be successfully used for estimating the solubility of SO2 in salt solutions at low partial pressures.
Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with ...outcomes with this combination for HR-MDS are incompletely understood.
We pooled patient data from 3 prospective trials evaluating HMA-venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan-Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations between clinical, cytogenetic, and molecular factors and outcomes.
A total of 80 patients (52 HMA-naïve, 28 HMA-failure) were included. ORR was 90% in HMA-naïve and 57% in HMA-failure. Median OS was 28.2 and 8.3 months in HMA-naïve and HMA-failure, respectively. Median EFS was 17.9 and 5.5 months in HMA-naïve and HMA-failure, respectively. In addition, 24/52 (46%) of the HMA-naïve and 3/28 (11%) of the HMA-failure patients proceeded to allogeneic stem cell transplantation (SCT). Factors associated with inferior outcomes were prior HMA failure, complex cytogenetics, trisomy 8, TP53 mutations, and RAS pathway mutations. Mutations in RNA splicing, DNA methylation, and ASXL1 appeared favorable. Blast percentage was not predictive of outcomes.
Knowledge of cytogenetic and molecular alterations may help identify which patients with HR-MDS benefit the most from venetoclax.
HMAs are the standard therapy for patients with myelodysplastic syndromes (MDS), but once patients develop HMA failure, survival remains dismal and FDA-approved treatment options nonexistent. ...Tapotoclax (AMG 176) directly induces apoptosis in cells dependent on MCL1 for survival. Given preclinical data establishing MCL1 as a promising therapeutic target in MDS, we hypothesized that tapotoclax may be safe and clinically active in patients with HMA failure MDS.
We designed a phase I study evaluating the safety and tolerability of tapotoclax in patients with HMA failure MDS (NCT05209152). Adult patients who did not respond to HMA after ≥4 cycles or progressed/relapsed at any time during HMA therapy were eligible and treated on study.
Between September 2022 and December 2023, 4 patients received tapotoclax 120 mg/m2 and 3 patients tapotoclax 240 mg/m2. The median number of cycles of tapotoclax received was 3. No dose-limiting toxicities (DLTs) were observed. The most common treatment-related adverse events (AEs) were nausea (85%), fatigue (57%), diarrhea (29%), and palpitations (14%). Regarding cardiac AEs, 1 patient experienced arrhythmias that were possibly related to tapotoclax but self-resolved. One patient had prolonged QTc intervals but had similar prolongation prior to tapotoclax exposure. No clinically significant troponin elevations were observed. No patients responded, and the trial was terminated. Four patients discontinued treatment due to lack of response, 1 proceeded to allogeneic stem cell transplantation, 1 discontinued from recurrent peritoneal cancer, and 1 discontinued per patient request and subsequent unrelated death. However, 2 of 3 patients who started with BM blasts ≥5% underwent unsustained blast reduction after cycle 3. All patients were transfusion-dependent with red blood cells (RBCs) at the time of enrollment, but 5 patients decreased RBC transfusions by ≥2 units between cycle 1 and 2, and 1 individual attained transfusion independence for 7 weeks.
This phase 1 study demonstrated that tapotoclax was safe and tolerated in a high-risk cohort of patients with HMA failure MDS. No DLTs were observed, and cardiac AEs self-resolved without dose reductions. Given its manageable toxicity profile and transient antileukemic and transfusion-independent effect, the use of tapotoclax in combination with HMA or other therapies may warrant further consideration.
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