Background
The outcome for diffuse large B‐cell lymphoma (DLBCL) patients has improved with the immunochemotherapy combination R‐CHOP. An increased rate of heart failure is well documented following ...this treatment, whereas incidence and outcome of other cardiac complications, for example myocardial infarction, are less well known.
Method
We identified 3548 curatively treated DLBCL patients in Sweden diagnosed between 2007 and 2014, and 35474 matched lymphoma‐free general population comparators. The incidence, characteristics and outcome of acute myocardial infarctions (AMIs) were assessed using population‐based registers up to 11 years after diagnosis. The rate of AMI was estimated using flexible parametric models.
Results
Overall, a 33% excess rate of AMI was observed among DLBCL patients compared with the general population (HR: 1.33, 95% CI: 1.14–1.55). The excess rate was highest during the first year after diagnosis and diminished after 2 years. High age, male sex and comorbidity were the strongest risk factors for AMI. Older patients (>70 years) with mild comorbidities (i.e. hypertension or diabetes) had a 61% higher AMI rate than comparators (HR: 1.61, 95% CI: 1.10–2.35), whereas the corresponding excess rate was 28% for patients with severe comorbidities (HR: 1.28, 95% CI: 1.01–1.64). Among younger patients (≤70), a short‐term excess rate of AMI was limited to those with severe comorbidities. There was no difference in AMI characteristics, pharmacological treatment or 30‐day survival among patients and comparators.
Conclusion
DLBCL patients have an increased risk of AMI, especially during the first 2 years, which calls for improved cardiac monitoring guided by age and comorbidities. Importantly, DLBCL was not associated with differential AMI management or survival.
Adipocyte mobilization of fatty acids (lipolysis) is instrumental for energy expenditure. Lipolysis displays both spontaneous (basal) and hormone-stimulated activity. It is unknown if lipolysis is ...important for future body weight gain and associated disturbed glucose metabolism, and this was presently investigated in subcutaneous adipocytes from two female cohorts before and after ≥10-year follow-up. High basal and low stimulated lipolysis at baseline predicted future weight gain (odds ratios ≥4.6) as well as development of insulin resistance and impaired fasting glucose/type 2 diabetes (odds ratios ≥3.2). At baseline, weight gainers displayed lower adipose expression of several established lipolysis-regulating genes. Thus, inefficient lipolysis (high basal/low stimulated) involving altered gene expression is linked to future weight gain and impaired glucose metabolism and may constitute a treatment target. Finally, low stimulated lipolysis could be accurately estimated in vivo by simple clinical/biochemical measures and may be used to identify risk individuals for intensified preventive measures.
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•Two long-term prospective cohorts on spontaneous weight change•Weight gainers display distinct differences in adipocyte lipolysis at baseline•Disturbed lipolysis conferred increased risk for impaired glucose metabolism•Baseline gene expression suggests primary defects in adipocyte lipolysis
Although differences in energy metabolism may promote weight gain, the involved tissue(s) are unknown. Here, Arner et al. report that altered subcutaneous fat cell lipolysis is independently linked to long-term weight gain and disturbed glucose metabolism. This may depend on primary defects in the expression of specific lipolytic regulators.
ABSTRACT
Using the VINTERGATAN cosmological zoom simulation, we explore the contributions of the in situ and accreted material, and the effect of galaxy interactions and mergers in the assembly of a ...Milky Way-like galaxy. We find that the initial growth phase of galaxy evolution, dominated by repeated major mergers, provides the necessary physical conditions for the assembly of a thick, kinematically hot disc populated by high-α/Fe stars, formed both in situ and in accreted satellite galaxies. We find that the diversity of evolutionary tracks followed by the simulated galaxy and its progenitors leads to very little overlap of the in situ and accreted populations for any given chemical composition. At a given age, the spread in α/Fe abundance ratio results from the diversity of physical conditions in VINTERGATAN and its satellites, with an enhancement in α/Fe found in stars formed during starburst episodes. Later, the cessation of the merger activity promotes the in situ formation of stars in the low-α/Fe regime, in a radially extended, thin and overall kinematically colder disc, thus establishing chemically bimodal thin and thick discs, in line with observations. We draw links between notable features in the Fe/H-α/Fe plane with their physical causes, and propose a comprehensive formation scenario explaining self-consistently, in the cosmological context, the main observed properties of the Milky Way.
How runaway stars boost galactic outflows Andersson, Eric P; Agertz, Oscar; Renaud, Florent
Monthly notices of the Royal Astronomical Society,
05/2020, Letnik:
494, Številka:
3
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Roughly 10 per cent of OB stars are kicked out of their natal clusters before ending their life as supernovae. These so-called runaway stars can travel hundreds of parsecs into the ...low-density interstellar medium, where momentum and energy from stellar feedback is efficiently deposited. In this work, we explore how this mechanism affects large-scale properties of the galaxy, such as outflows. To do so we use a new model that treats OB stars and their associated feedback processes on a star-by-star basis. With this model, we compare two hydrodynamical simulations of Milky Way-like galaxies, one where we include runaways, and one where we ignore them. Including runaway stars leads to twice as many supernovae explosions in regions with gas densities ranging from $10^{-5}\, \mathrm{\,cm^{-3}}$ to $10^{-3}\, \mathrm{\,cm^{-3}}$. This results in more efficient heating of the inter-arm regions, and drives strong galactic winds with mass loading factors boosted by up to one order of magnitude. These outflows produce a more massive and extended multiphase circumgalactic medium, as well as a population of dense clouds in the halo. Conversely, since less energy and momentum is released in the dense star-forming regions, the cold phase of the interstellar medium is less disturbed by feedback effects.
Ibrutinib, a Bruton's tyrosine kinase inhibitor is approved for relapsed/refractory and del(17p)/TP53 mutated chronic lymphocytic leukemia. Discrepancies between clinical trials and routine ...health-care are commonly observed in oncology. Herein we report real-world results for 95 poor prognosis Swedish patients treated with ibrutinib in a compassionate use program. Ninety-five consecutive patients (93 chronic lymphocytic leukemia, 2 small lymphocytic leukemia) were included in the study between May 2014 and May 2015. The median age was 69 years. 63% had del(17p)/TP53 mutation, 65% had Rai stage III/IV, 28% had lymphadenopathy ≥10cm. Patients received ibrutinib 420 mg once daily until progression. At a median follow-up of 10.2 months, the overall response rate was 84% (consistent among subgroups) and 77% remained progression-free. Progression-free survival and overall survival were significantly shorter in patients with del(17p)/TP53 mutation (P=0.017 and P=0.027, log-rank test); no other factor was significant in Cox proportional regression hazards model. Ibrutinib was well tolerated. Hematomas occurred in 46% of patients without any major bleeding. Seven patients had Richter's transformation. This real-world analysis on consecutive chronic lymphocytic leukemia patients from a well-defined geographical region shows the efficacy and safety of ibrutinib to be similar to that of pivotal trials. Yet, del(17p)/TP53 mutation remains a therapeutic challenge. Since not more than half of our patients would have qualified for the pivotal ibrutinib trial (RESONATE), our study emphasizes that real-world results should be carefully considered in future with regards to new agents and new indications in chronic lymphocytic leukemia.
•First trial comparing a conjugated vaccine with a capsular polysaccharide vaccine against pneumococci in CLL.•Improved immunological response against pneumococci with a conjugated vaccine in ...patients with CLL.•Long disease duration and low IgG levels associated with poor response to pneumococcal vaccine in CLL.
To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent pneumococcal conjugated vaccine (PCV13), Prevenar13®, compared to a 23-valent pneumococcal polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response.
Streptococcus pneumoniae causes substantial morbidity in patients with CLL, a group known to respond poorly to polysaccharide vaccines. Comparative studies with conjugated vaccines are lacking.
128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n = 63) or PPSV23 (n = 65) after stratification by IgG level and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, and at one and six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA).
PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. PPSV23 did not trigger a better immune response than PCV13 for any of the serotypes, regardless of analysis method or time point of analysis. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated.
In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for most serotypes common for the two vaccines. We therefore propose that PCV13 should be included in vaccination programs against Streptococcus pneumoniae for CLL patients and administered as early as possible during the course of the disease.
Despite the wealth of evidence regarding physical training strategies in soccer, there is little information regarding soccer-specific concurrent training and the effects of training order. The ...current study aimed to: i) quantify the effects of concurrent high-intensity run-based training (HIT) and strength- and power-based training (STR) on soccer-specific performance, and ii) investigate the order effect of completing HIT and STR either first or second within training sessions. Eighteen semi- and fully-professional players completed a battery of field- and gym-based tests before and after a 5-week pre-season training intervention. Players were pair-matched and completed 3 sessions per week of HIT followed by STR (n=9) or STR followed by HIT (n=9). ANCOVA tests revealed no differences between groups for changes in any of the measures (p>0.05). However, a training effect was observed for all measures (p<0.05), with 10-m sprint, 6×30-m repeated sprint, 40-m agility and Yo-Yo test performances improving by 1.8±2.6%, 1.3±1.8%, 1.0±1.5% and 19.4±23.4%, respectively (n=18). In conclusion, there was a positive effect of the concurrent training approach on key measures of soccer performance, but the order of completing HIT and STR appears inconsequential to performance adaptations.
ABSTRACT
Using the cosmological zoom simulation VINTERGATAN, we present a new scenario for the onset of star formation at the metal-poor end of the low-α/Fe sequence in a Milky Way-like galaxy. In ...this scenario, the galaxy is fuelled by two distinct gas flows. One is enriched by outflows from massive galaxies, but not the other. While the former feeds the inner galactic region, the latter fuels an outer gas disc, inclined with respect to the main galactic plane, and with a significantly poorer chemical content. The first passage of the last major merger galaxy triggers tidal compression in the outer disc, which increases the gas density and eventually leads to star formation, at a metallicity 0.75 dex lower than the inner galaxy. This forms the first stars of the low-α/Fe sequence. These in situ stars have halo-like kinematics, similar to what is observed in the Milky Way, due to the inclination of the outer disc that eventually aligns with the inner one via gravitational torques. We show that this tilting disc scenario is likely to be common in Milky Way-like galaxies. This process implies that the low-α/Fe sequence is populated in situ, simultaneously from two formation channels, in the inner and the outer galaxy, with distinct metallicities. This contrasts with purely sequential scenarios for the assembly of the Milky Way disc and could be tested observationally.
The worldwide obesity epidemic
makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that ...excess body fat is associated with decreased adipose lipid removal rates
. Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived
C in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.
We have calculated optimal frequency scaling factors for the B3LYP/ 6-311+G(d,p) method for fundamental vibrational frequencies on the basis of a set of 125 molecules. Using the new scaling factor, ...the vibrational frequencies calculated with the triple-ζ basis set 6-311+G(d,p) give significantly better accuracy than those calculated with the double-ζ 6-31G(d) basis set. Scale factors were also determined for low-frequency vibrations using the molecular set of 125 molecules and for zero-point energies using a smaller set of 40 molecules. We have studied the effect on the calculated vibrational frequencies for various combinations of diffuse and polarization functions added to the triple-ζ 6-311G basis set. The 6-311+G(d,p) basis set is found to give almost converged frequencies for most molecules, and we conclude that our optimum scaling factors are valid for the basis sets 6-311G(d,p) to 6-311++G(3df,3pd). The new scale factors are 0.9679 for vibrational frequencies, 1.0100 for low-frequency vibrations, and 0.9877 for zero-point vibrational energies.
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