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.
Optimal coverage of Pseudomonas aeruginosa is challenging in febrile neutropenic patients due to a progressive increase in antibiotic resistance worldwide. We aimed to detail current rates of ...resistance to antibiotics recommended by international guidelines for P. aeruginosa isolated from bloodstream infections (BSI) in patients with hematologic malignancies. Secondarily, we aimed to describe how many patients received inappropriate empirical antibiotic treatment (IEAT) and its impact on mortality. We conducted a retrospective, multicenter cohort study of the last 20 BSI episodes caused by P. aeruginosa in patients with hematologic malignancies from across 14 university hospitals in Spain. Of the 280 patients with hematologic malignancies and BSI caused by P. aeruginosa, 101 (36%) had strains resistant to at least one of the β-lactam antibiotics recommended in international guidelines, namely, cefepime, piperacillin-tazobactam, and meropenem. Additionally, 21.1% and 11.4% of the strains met criteria for MDR and XDR P. aeruginosa, respectively. Even if international guidelines were followed in most cases, 47 (16.8%) patients received IEAT and 66 (23.6%) received inappropriate β-lactam empirical antibiotic treatment. Thirty-day mortality was 27.1%. In the multivariate analysis, pulmonary source (OR 2.22, 95% CI 1.14 to 4.34) and IEAT (OR 2.67, 95% CI 1.37 to 5.23) were factors independently associated with increased mortality. We concluded that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines, which is associated with frequent IEAT and higher mortality. New therapeutic strategies are needed.
Bloodstream infection (BSI) caused by P. aeruginosa is related with an elevated morbidity and mortality in neutropenic patients. For this reason, optimal antipseudomonal coverage has been the basis of all historical recommendations in the empirical treatment of febrile neutropenia. However, in recent years the emergence of multiple types of antibiotic resistances has posed a challenge in treating infections caused by this microorganism. In our study we postulated that P. aeruginosa-causing BSI in patients with hematologic malignancies is commonly resistant to antibiotics recommended in international guidelines. This observation is associated with frequent IEAT and increased mortality. Consequently, there is a need for a new therapeutic strategy.
Autophagy in Hematological Malignancies García Ruiz, Olga; Sánchez-Maldonado, José Manuel; López-Nevot, Miguel Ángel ...
Cancers,
10/2022, Volume:
14, Issue:
20
Journal Article
Peer reviewed
Open access
Autophagy is a highly conserved metabolic pathway via which unwanted intracellular materials, such as unfolded proteins or damaged organelles, are digested. It is activated in response to conditions ...of oxidative stress or starvation, and is essential for the maintenance of cellular homeostasis and other vital functions, such as differentiation, cell death, and the cell cycle. Therefore, autophagy plays an important role in the initiation and progression of tumors, including hematological malignancies, where damaged autophagy during hematopoiesis can cause malignant transformation and increase cell proliferation. Over the last decade, the importance of autophagy in response to standard pharmacological treatment of hematological tumors has been observed, revealing completely opposite roles depending on the tumor type and stage. Thus, autophagy can promote tumor survival by attenuating the cellular damage caused by drugs and/or stabilizing oncogenic proteins, but can also have an antitumoral effect due to autophagic cell death. Therefore, autophagy-based strategies must depend on the context to create specific and safe combination therapies that could contribute to improved clinical outcomes. In this review, we describe the process of autophagy and its role on hematopoiesis, and we highlight recent research investigating its role as a potential therapeutic target in hematological malignancies. The findings suggest that genetic variants within autophagy-related genes modulate the risk of developing hemopathies, as well as patient survival.
Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite ...the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular (GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. In the multivariate analysis, CART was confirmed to be similar to alloHCT for the primary study endpoint (progression-free survival) (hazard ratio HR 0.92, CI95%:0.56-1.51, p = 0.75). Furthermore, when the analysis was limited to only patients with chemo-sensitive diseases (complete and partial response) at infusion (CART = 26, alloHCT=93), no differences were reported (progression-free survival at month +18: 65% versus 55%, p = 0.59). However, CART had lower non-relapse mortality (HR 0.34, 95% CI: 0.13-0.85, p = 0.02). Given the lower toxicity and similar survival outcomes, these results suggest the use of CART before alloHCT.
To analyze prognostic factors associated with survival in patients after intraoperative electrons containing resective surgical rescue of locally recurrent rectal cancer (LRRC).
From January 1995 to ...December 2011, 60 patients with LRRC underwent extended surgery (n=38: multiorgan 43%, bone 28%, soft tissue 38%) or nonextended (n=22) surgical resection, including a component of intraoperative electron-beam radiation therapy (IOERT) to the pelvic recurrence tumor bed. Twenty-eight (47%) of these patients also received external beam radiation therapy (EBRT) (range, 30.6-50.4 Gy). Survival outcomes were estimated by the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses.
The median follow-up time was 36 months (range, 2-189 months), and the 1-year, 3-year, and 5-year rates for locoregional control (LRC) and overall survival (OS) were 86%, 52%, and 44%; and 78%, 53%, 43%, respectively. On multivariate analysis, R1 resection, EBRT at the time of pelvic rerecurrence, no tumor fragmentation, and non-lymph node metastasis retained significance with regard to LRR. R1 resection and no tumor fragmentation showed a significant association with OS after adjustment for other covariates.
EBRT treatment integrated for rescue, resection radicality, and not involved fragmented resection specimens are associated with improved LRC in patients with locally recurrent rectal cancer. Additionally, tumor fragmentation could be compensated by EBRT. Present results suggest that a significant group of patients with LRRC may benefit from EBRT treatment integrated with extended surgery and IOERT.
Purpose
To analyze prognostic factors and long-term outcomes in patients with locally recurrent pelvic cancer (LRPC) treated with a multidisciplinary approach.
Methods and materials
From January 1995 ...to December 2011, 81 patients rectal (47 %); gynecologic (39 %); retroperitoneal sarcoma (14 %) underwent extended surgery multiorgan (58 %), bone (35 %), vascular (9 %), soft tissue (63 %) and intraoperative electron beam radiation therapy (IOERT) to treat recurrent tumors in the pelvic region. Thirty-five patients (43 %) received external beam radiotherapy (EBRT). Survival was estimated using the Kaplan–Meier method, and risk factors were identified using univariate and multivariate analysis.
Results
Median follow-up was 39 months (6–189 months); the 1- 3- and 5-year rates of locoregional control (LRC) were 83, 53, and 41 %, respectively. Univariate Cox proportional hazard analysis revealed worse LRC in patients who did not receive integrated EBRT as rescue treatment of pelvic recurrence (
p
= 0.003) or underwent non-radical resection (
p
= 0.01). In the multivariate analysis EBRT, non-radical resection, and tumor fragmentation retained significance (
p
= 0.002,
p
= 0.004, and
p
= 0.05, respectively).
Conclusions
Radical resection, absence of tumor fragmentation and addition of EBRT for rescue are associated with improved LRC in patients with LRPC. Our results suggest that this group can benefit from EBRT combined with extended surgical resection and IOERT.
Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the
and
loci influence the risk of developing invasive aspergillosis (IA). We conducted a two-stage case control study ...including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the
genotype had a significantly increased risk of developing IA (
= 0.00022). We also found that carriers of the
allele showed decreased serum levels of TNFSF14 protein (
= 0.0027), and that their macrophages had a decreased fungicidal activity (
= 0.048). In addition, we observed that each copy of the
allele increased the risk of IA by 60% (
= 0.0017), whereas each copy of the
allele was estimated to decrease the risk of developing the disease (
= 0.0029). Mechanistically, we found that carriers of the risk
allele showed increased numbers of CD38+IgM-IgD- plasmablasts in blood (
= 0.00086), whereas those harboring two copies of the allele had decreased serum concentrations of thymic stromal lymphopoietin (
= 0.00097). Finally, we also found that carriers of the protective
allele had decreased numbers of CD27-IgM-IgD- B cells (
= 0.00087) and significantly lower numbers of CD14+ and CD14+CD16- cells (
= 0.00018 and 0.00023). Altogether, these results suggest a role of the
genes in determining IA risk.
En Ensifera (Tettigoniidae: Phaneropterinae), los machos producen señales acústicas mediante estridulación tegminal; estas señales funcionan en primera instancia para atraer hembras conespecíficas ...sexualmente receptivas. El estudio de la bioacústica es, además, una herramienta complementaria en estudios morfológicos tradicionales, ya que estas señales son especie-específicas y permiten diferenciar especies morfológicamente similares (crípticas). Las señales acústicas representan un sistema importante de comunicación intra e interespecífico. Los miembros de la familia Tettigoniidae se destacan por la producción de señales acústicas que frecuentemente son inaudibles al oído humano frecuencia (f) > de 20 kHz. México posee una amplia diversidad de insectos, sin embargo, pocos estudios se han enfocado al conocimiento del repertorio acústico de éstos. En este trabajo se describe por primera vez el canto ultrasónico de llamado de Obolopteryx eurycerca Barrientos-Lozano & Rocha-Sánchez, 2016. Ejemplares en estudio se recolectaron en el municipio de Hidalgo, Tamaulipas, México. La señal acústica de llamado de los machos consiste en la producción de equemas de tres sílabas, que se emiten en forma continua por periodos largos de tiempo (± 1h). Se compara la señal acústica de O. eurycerca con la de O. castanea (Rehn & Hebard, 1914) y se discuten las ventajas de la comunicación acústica ultrasónica en Ensifera.
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