Summary
The International Prognostic Index (IPI) is the most widely used score for non‐Hodgkin lymphoma but lacks the ability to identify a high‐risk population in diffuse large B‐cell lymphoma ...(DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red‐cell distribution width (RDW) has been associated with inflammation and beta‐2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R‐CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG‐PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression‐free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3–4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high‐risk subgroup with five‐year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)‐IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real‐life practice without additional tests. Compared to R‐IPI, it shows a more precise high‐risk assessment and risk discrimination for both PFS and OS.
Abstract
Objectives
To describe current resistance to the β-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB).
Methods
...Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated.
Results
Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three β-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%; P < 0.001). Thirty day mortality was 14.6%, reaching 21.6% in patients receiving IEAT.
Conclusions
Current resistance to empirical β-lactams recommended in febrile neutropenia guidelines is exceedingly high and IEAT rates are greater than desired. There is an urgent need to adapt guidelines to current epidemiology and better identify patients with a high risk of developing MDR GNB infection.
This article investigates the presence of unwarranted between court disparities in England and
Wales, examining whether they can be explained by non-legal contextual factors such as the organisation ...of the court and socio-economic composition of the area. In contrast with previous literature, we emphasise the importance of controlling for a wide range of legally relevant case characteristics. The findings reveal that some preliminary startling trends, such as more severe sentencing in courts located in neighbourhoods with high proportions of Muslim residents, are in fact accounted for by differences in the cases reviewed across courts. These findings call into question the validity of previous studies exploring the influence of the context on sentencing that did not adequately
control for legal factors.
CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be ...designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA
T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells were transduced with an NKG2D-4-1BB-CD3z-CAR. CAR-NKAE cells exhibited no evidence of genetic abnormalities. Although memory T cells were more stably transduced, CAR-NKAE cells exhibited greater in vitro cytotoxicity against MM cells, while showing minimal activity against healthy cells. In vivo, CAR-NKAE cells mediated highly efficient abrogation of MM growth, and 25% of the treated mice remained disease free. Overall, these results demonstrate that it is feasible to modify autologous NKAE cells from MM patients to safely express a NKG2D-CAR. Additionally, autologous CAR-NKAE cells display enhanced antimyeloma activity demonstrating that they could be an effective strategy against MM supporting the development of NKG2D-CAR-NK-cell therapy for MM.
Leaves of Mediterranean evergreen tree species experience a reduction in net CO2 assimilation (AN) and mesophyll conductance to CO2 (gm) during aging and senescence, which would be influenced by ...changes in leaf anatomical traits at cell level. Anatomical modifications can be accompanied by the dismantling of photosynthetic apparatus associated to leaf senescence, manifested through changes at biochemical level (i.e., lower nitrogen investment in photosynthetic machinery). However, the role of changes in leaf anatomy at cell level and nitrogen content in gm and AN decline experienced by old non-senescent leaves of evergreen trees with long leaf lifespan is far from being elucidated. We evaluated age-dependent changes in morphological, anatomical, chemical and photosynthetic traits in Quercus ilex subsp. rotundifolia Lam., an evergreen oak with high leaf longevity. All photosynthetic traits decreased with increasing leaf age. The relative change in cell wall thickness (Tcw) was less than in chloroplast surface area exposed to intercellular air space (Sc/S), and Sc/S was a key anatomical trait explaining variations in gm and AN among different age classes. The reduction of Sc/S were related to ultrastructural changes in chloroplasts associated to leaf aging, with a concomitant reduction in cytoplasmic nitrogen. Changes in leaf anatomy and biochemistry were responsible for the age-dependent modifications in gm and AN. These findings revealed a gradual physiological deterioration related to the dismantling of the photosynthetic apparatus in older leaves of Q. ilex subsp. rotundifolia.
Strong evidence of racial and ethnic disparities has been documented in recent government‐led reports, suggesting the presence of discrimination in sentencing, with Black and ethnic minority ...defendants being systematically sentenced more harshly than their white counterparts. However, we still do not know how these disparities come about as most of the sentencing research has relied on quantitative designs focused on documenting the problem, rather than exploring its causes. In this exploratory study we use qualitative interviews with criminal law barristers to explore the different mechanisms that may give rise to these disparities. From our interviews we identified two predominant causal mechanisms: the differential consideration of mitigating and aggravating factors and indirect discrimination arising from defendants’ socio‐economic backgrounds and over‐policing. Based on these findings, we suggest effective strategies such as explicitly listing social deprivation as a mitigating factor in the sentencing guidelines and increasing judicial diversity for redressing these disparities.
Analyses of crime based upon aggregate counts of different crime types have restricted value, because they count all crime types equally irrespective of the harm caused. In response to this problem, ...a series of weighted measures of crime harm have been proposed. In this short contribution, we contend that the use of some crime harm metrics to inform police deployment practices has the potential to reinforce ethnic disparities in the criminal justice system through the creation of unintended negative feedback loops. We focus our analysis on the Cambridge Crime Harm Index and the Office for National Statistics (ONS) Crime Severity Score, the preeminent crime harm indexes in England and Wales. We conclude that the ONS Crime Severity Score, which is based on mean sentencing outcomes,
does
give cause for concern in some contexts. There is currently no evidence that the Cambridge Crime Harm Index, based on sentencing guidelines, presents the same problems.
Abstract
Empirical research has repeatedly focused on the potential existence of sentencing disparities. In particular, a growing number of studies have used multilevel models to quantify the extent ...that ‘similar’ offences are treated alike in different courts. This reliance on multilevel models has resulted in a natural focus on differences in the mean sentence awarded between courts, with the amount of within-group variability generally assumed to be the same in each court. In this paper, we show how multilevel models can be extended by allowing the magnitude of within-court differences to be different in each court. This provides a natural framework to connect between-court disparities with the sentencing differences that are thought to originate between judges operating within the same court, particularly in the absence of more fine-grained sentencing data about the judge residing in each case. Focusing specifically on cases of assault sentenced in 2011, we show that there are substantial differences in the range of sentences awarded in different courts, with the range almost twice as large in some courts. We also find that it is those courts that appear to show the traits of more homogeneous sentencing that sentence more harshly and that offences involving the presence of a weapon or evidence of good character and/or exemplary conduct were associated with higher levels of internal consistency.
Abstract
Little is known about how the Sentencing Council’s guidance to treat intoxication as aggravation is applied in practice. With reference to assault offences, this study examines: whether ...intoxication has an aggravating effect; whether this is moderated through other characteristics of the case; and whether any effect is consistent across Crown Court locations. The probability of custody and sentence severity are modelled using (ordered) logit multilevel models and data from the Crown Court Sentencing Survey. The probability of receiving a custodial or severe sentence when intoxication features is increased, however, is moderated if the offence is deemed an isolated incident. Effects are relatively consistent across Crown Court locations, however ongoing monitoring of how intoxication shapes sentencing practice it is encouraged.
We assess the use of sentencing guidelines for assault issued in England and Wales, and the consistency with which they are applied by judges in the Crown Court. We use data from the Crown Court ...Sentencing Survey (CCSS), which records data on legal factors considered in the sentencing guidelines. This gives us access to a wide range of explanatory variables, allowing us to produce more robust findings about consistency in sentencing. We first employ a standard regression model to determine how guideline factors affect sentence outcomes empirically. Second, a random slopes multilevel model is used to analyse whether these factors have been consistently applied across different Crown Court centres. Our results point to a substantial degree of consistency in sentencing.
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