Introduction
Inv(3)(q21.3q26.2)/t(3;3)(q21.3;q26.2) is a rare poor prognosis cytogenetic abnormality present in acute myeloid leukemia (AML) and other myeloid neoplasms.
Objective
The aim of this ...study was to evaluate the outcome of a cohort of 61 patients with newly diagnosed AML with inv(3)/t(3;3) treated with homogeneous intensive chemotherapy protocols conducted by the Spanish PETHEMA and CETLAM cooperative groups between 1999 and 2017.
Methods
In this retrospective study the main clinical and biologic parameters were collected. The complete response (CR) rate, the cumulative incidence of relapse (CIR) and the overall survival (OS) were calculated. An analysis of prognostic factors for survival was performed.
Results
Sixty‐one patients received induction and only 18 (29%) achieved CR (median age, 46 years). Allogeneic hematopoietic stem cell transplantation (alloHSCT) was performed in 36 patients (59%), 15 with active disease. One‐ and 4‐year CIR were 52% and 56%. One‐ and 4‐year OS probabilities were 41% and 13%. By multivariate analysis monosomal karyotype (MK) was associated with poorer OS (HR 2.0, P = .017).
Conclusion
Inv(3)/t(3;3) AML is a poor prognosis entity with low response to standard chemotherapy and to alloHSCT because of frequent and early relapse. MK was associated with a poorer prognosis. Improved therapeutic strategies are clearly needed.
Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the ...effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.
•In intermediate-risk AML, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.•Combined evaluation of NPM1 mutation and FLT3-ITD burden might contribute to identify patients who benefit from early allogeneic HSCT.
In this study, we suggest optimizing the methodology to determine the Cohesion Index (Icd) in order to avoid mistaken characterizations due to powder bulk density. For this purpose, five different ...excipients, with different bulk densities and of different chemical nature, were compressed at different heights. Their compression and their tablet characterization enable establishing a powder weight for compression in accordance with its bulk density. Therefore, the resulting tablet will have a height within a defined range of heights where it has no critical effects on its hardness. Then, the impact of this optimization is shown in a formula development, one of the main SeDeM's applications. A mathematical equation was used to calculate the theoretical amount of excipient to formulate the API according to both methodologies. The compression results demonstrate that the characterization with the NM-Icd is more accurate than the previous one while preserving its simplicity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The role of high-intensity exercise and other emerging risk factors in lone atrial fibrillation (Ln-AF) epidemiology is still under debate. The aim of this study was to analyse the contribution of ...each of the emerging risk factors and the impact of physical activity dose in patients with Ln-AF.
Patients with Ln-AF and age- and sex-matched healthy controls were included in a 2:1 prospective case-control study. We obtained clinical and anthropometric data transthoracic echocardiography, lifetime physical activity questionnaire, 24-h ambulatory blood pressure monitoring, Berlin questionnaire score, and, in patients at high risk for obstructive sleep apnoea (OSA) syndrome, a polysomnography. A total of 115 cases and 57 controls were enrolled. Conditional logistic regression analysis associated height odds ratio (OR) 1.06 1.01-1.11, waist circumference (OR 1.06 1.02-1.11), OSA (OR 5.04 1.44-17.45), and 2000 or more hours of cumulative high-intensity endurance training to a higher AF risk. Our data indicated a U-shaped association between the extent of high-intensity training and AF risk. The risk of AF increased with an accumulated lifetime endurance sport activity ≥ 2,000 h compared with sedentary individuals (OR 3.88 1.55-9.73). Nevertheless, a history of <2000 h of high-intensity training protected against AF when compared with sedentary individuals (OR 0.38 0.12-0.98).
A history of ≥ 2,000 h of vigorous endurance training, tall stature, abdominal obesity, and OSA are frequently encountered as risk factors in patients with Ln-AF. Fewer than 2000 total hours of high-intensity endurance training associates with reduced Ln-AF risk.
Detecting and managing frailty at early stages can prevent disability and other adverse outcomes. The study aim was to evaluate whether a multifactorial intervention program could modify physical and ...cognitive frailty parameters in elderly individuals.
We conducted a multicenter, randomized, single-blind, parallel-group trial in community-living prefrail/frail elderly individuals in Barcelona. A total of 352 patients, aged ≥65 years old with positive frailty screening, was randomized into two groups to receive a 12-week multidisciplinary intervention or usual care, with concealed allocation. The intervention consisted of: exercise training, intake of hyperproteic nutritional shakes, memory training, and medication review. Main outcome assessments with multivariate analysis were conducted at 3 and 18 months.
A total of 347 participants (98.6%) completed the study, mean age 77.3 years, 89 prefrail subjects (25.3%), and 75.3% female (n = 265). Eighteen-month assessments were performed in 76% of the sample. After 3 and 18 months, adjusted means difference between-groups showed significant improvements for the intervention group in all comparisons: Short Physical Performance Battery score improved 1.58 and 1.36 points (p < .001), handgrip strength 2.84 and 2.49 kg (p < .001), functional reach 4.3 and 4.52 cm (p < .001), and number of prescriptions decreased 1.39 and 1.09 (p < .001), respectively. Neurocognitive battery also showed significant improvements across all dimensions at 3 and 18 months.
A physical, nutritional, neurocognitive, and pharmacological multifaceted intervention was effective in reversing frailty measures both at short-term and 18 months. Lasting benefits of a multi-intervention program among frail elderly individuals encourage its prioritization.
IMPORTANCE More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, there is little evidence about the effect of continuous positive airway pressure (CPAP) ...treatment on blood pressure in patients with resistant hypertension. OBJECTIVE To assess the effect of CPAP treatment on blood pressure values and nocturnal blood pressure patterns in patients with resistant hypertension and OSA. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized, multicenter clinical trial of parallel groups with blinded end point design conducted in 24 teaching hospitals in Spain involving 194 patients with resistant hypertension and an apnea-hypopnea index (AHI) of 15 or higher. Data were collected from June 2009 to October 2011. INTERVENTIONS CPAP or no therapy while maintaining usual blood pressure control medication. MAIN OUTCOMES AND MEASURES The primary end point was the change in 24-hour mean blood pressure after 12 weeks. Secondary end points included changes in other blood pressure values and changes in nocturnal blood pressure patterns. Both intention-to-treat (ITT) and per-protocol analyses were performed. RESULTS A total of 194 patients were randomly assigned to receive CPAP (n = 98) or no CPAP (control; n = 96). The mean AHI was 40.4 (SD, 18.9) and an average of 3.8 antihypertensive drugs were taken per patient. Baseline 24-hour mean blood pressure was 103.4 mm Hg; systolic blood pressure (SBP), 144.2 mm Hg; and diastolic blood pressure (DBP), 83 mm Hg. At baseline, 25.8% of patients displayed a dipper pattern (a decrease of at least 10% in the average nighttime blood pressure compared with the average daytime blood pressure). The percentage of patients using CPAP for 4 or more hours per day was 72.4%. When the changes in blood pressure over the study period were compared between groups by ITT, the CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg 95% CI, 0.6 to 5.6; P = .02) and 24-hour DBP (3.2 mm Hg 95% CI, 1.0 to 5.4; P = .005), but not in 24-hour SBP (3.1 mm Hg 95% CI, −0.6 to 6.7; P = .10) compared with the control group. Moreover, the percentage of patients displaying a nocturnal blood pressure dipper pattern at the 12-week follow-up was greater in the CPAP group than in the control group (35.9% vs 21.6%; adjusted odds ratio OR, 2.4 95% CI, 1.2 to 5.1; P = .02). There was a significant positive correlation between hours of CPAP use and the decrease in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). CONCLUSIONS AND RELEVANCE Among patients with OSA and resistant hypertension, CPAP treatment for 12 weeks compared with control resulted in a decrease in 24-hour mean and diastolic blood pressure and an improvement in the nocturnal blood pressure pattern. Further research is warranted to assess longer-term health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00616265
Obstructive sleep apnea (OSA) is an independent risk factor for stroke, but little is known about the role of continuous positive airway pressure (CPAP) on mortality in patients with stroke.
To ...analyze the independent impact of long-term CPAP treatment on mortality in patients with ischemic stroke.
Prospective observational study in 166 patients with ischemic stroke. Sleep study was performed in all of them and CPAP treatment was offered in the case of moderate to severe cases. Patients were followed-up for 5 years to analyze the risk of mortality.
Of 223 patients consecutively admitted for stroke, a sleep study was performed on 166 of them (2 mo after the acute event). Thirty-one had an apnea-hypopnea index (AHI) of less than 10; 39 had an AHI between 10 and 19, and 96 had an AHI of 20 or greater. CPAP treatment was offered when AHI was 20 or greater. Patients were followed up in our outpatient clinic at 1, 3, and 6 months, and for every 6 months thereafter for 5 years (prospective observational study). Mortality data were recorded from our computer database and official death certificates. The mean age of subjects was 73.3 +/- 11 years (59% males), and the mean AHI was 26 (for all patients with a predominance of obstructive events). Patients with an AHI of 20 or greater who did not tolerate CPAP (n = 68) showed an increase adjusted risk of mortality (hazards ratio HR, 2.69; 95% confidence interval CI, 1.32-5.61) compared with patients with an AHI of less than 20 (n = 70), and an increased adjusted risk of mortality (HR, 1.58; 95% CI, 1.01-2.49; P = 0.04) compared with patients with moderate to severe OSA who tolerated CPAP (n = 28). There were no differences in mortality among patients without OSA, patients with mild disease, and patients who tolerated CPAP.
Our results suggest that long-term CPAP treatment in moderate to severe OSA and ischemic stroke is associated with a reduction in excess risk of mortality.
Discarded human donor organs have been shown to provide decellularized extracellular matrix (dECM) scaffolds suitable for organ engineering. The quest for appropriate cell sources to satisfy the need ...of multiple cells types in order to fully repopulate human organ-derived dECM scaffolds has opened new venues for the use of human pluripotent stem cells (hPSCs) for recellularization. In addition, three-dimensional (3D) bioprinting techniques are advancing towards the fabrication of biomimetic cell-laden biomaterial constructs. Here, we review recent progress in decellularization/recellularization and 3D bioprinting technologies, aiming to fabricate autologous tissue grafts and organs with an impact in regenerative medicine.
A preformulation study of an oral lyophilisate with cetirizine dihydrochloride (CTZ) as active ingredient, mannitol and PVP K30 as bulking agents is presented. CTZ shown a humidity content of 0.150% ...and a spontaneous hygroscopicity of 0.200% (both determined by SeDeM diagram), demonstrating an adequate stability behavior in solid form. A design of experiments (DoE) performed with both mannitol and PVP K30, followed by a simple factorial design (32) has determined the optimum combination of excipients and CTZ, and showed that a higher proportion of PVP K30 was able to prevent metastable forms generated by mannitol.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: This research aims to study the role of people with intellectual disability in taking decisions regarding the support provided under the supported living model.
Method: Interviews were ...conducted with 13 people with intellectual disability, and six support professionals with experience working in organisations offering personalised support. These covered the person's pathway, the support received, and their role in controlling this. Interviews were recorded and transcribed, and the data analysed through thematic content analysis in two consecutive phases, one descriptive and one interpretative.
Results: While supported living aims to provide personalised solutions to individual needs, support is conditioned to a greater or lesser extent by the assessment professionals make regarding the autonomy of the person with intellectual disability.
Conclusions: In order for individuals to make advances in their choice of, and control over, support received, people with intellectual disability must be empowered, and professional practices adapted through training.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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