Treatment options for patients with secondary acute myeloid leukemia (sAML) and AML with myeloid-related changes (AMLMRC) aged 60 to 75 years are scarce and unsuitable. A pivotal trial showed that ...CPX-351 improved complete remission with/without incomplete recovery (CR/CRi) and overall survival (OS) as compared with standard "3+7" regimens. We retrospectively analyze outcomes of 765 patients with sAML and AML-MRC aged 60 to 75 years treated with intensive chemotherapy, reported to the PETHEMA registry before CPX-351 became available. The CR/CRi rate was 48%, median OS was 7.6 months (95% confidence interval CI: 6.7-8.5) and event-free survival (EFS) 2.7 months (95% CI: 2-3.3), without differences between intensive chemotherapy regimens and AML type. Multivariate analyses identified age ≥70 years, Eastern Cooperative Oncology Group performance status ≥1 as independent adverse prognostic factors for CR/CRi and OS, while favorable/intermediate cytogenetic risk and NPM1 were favorable prognostic factors. Patients receiving allogeneic stem cell transplant (HSCT), autologous HSCT, and those who completed more consolidation cycles showed improved OS. This large study suggests that classical intensive chemotherapy could lead to similar CR/CRi rates with slightly shorter median OS than CPX-351.
Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the ...role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4
goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.
Impact of plasmapheresis on severe COVID-19 Fonseca-González, G; Alamilla-Sánchez, M; García-Macas, V ...
Scientific reports,
01/2023, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The clinical course of COVID-19 may show severe presentation, potentially involving dynamic cytokine storms and T cell lymphopenia, which are leading causes of death in patients with SARS-CoV-2 ...infection. Plasma exchange therapy (PLEX) effectively removes pro-inflammatory factors, modulating and restoring innate and adaptive immune responses. This clinical trial aimed to evaluate the impact of PLEX on the survival of patients with severe SARS-CoV-2 and the effect on the cytokine release syndrome. Hospitalized patients diagnosed with SARS-CoV-2 infection and cytokine storm syndrome were selected to receive 2 sessions of PLEX or standard therapy. Primary outcome was all-cause 60-days mortality; secondary outcome was requirement of mechanical ventilation, SOFA, NEWs-2 scores modification, reduction of pro-inflammatory biomarkers and hospitalization time. Twenty patients received PLEX were compared against 40 patients receiving standard therapy. PLEX reduced 60-days mortality (50% vs 20%; OR 0.25, 95%CI 0.071-0.880; p = 0.029), and this effect was independent from demographic variables and drug therapies used. PLEX significantly decreased SOFA, NEWs-2, pro-inflammatory mediators and increased lymphocyte count, accompanied with a trend to reduce affected lung volume, without effect on SatO
/FiO
indicator or mechanical ventilation requirement. PLEX therapy provided significant benefits of pro-inflammatory clearance and reduction of 60-days mortality in selected patients with COVID-19, without significant adverse events.
Cervical human papillomavirus (HPV+) infection is associated with an increased risk of cervical dysplasia. Although the frequency of HPV+ in systemic lupus erythematosus (SLE) has been investigated ...in some races its prevalence in Hispanic women is still unknown. This cross-sectional study evaluated the prevalence of cervical HPV+ in Mexican women with SLE (n = 34) or rheumatoid arthritis (RA) (n = 43) and in healthy controls (n = 146). These women were interviewed about risk factors for sexually transmitted infections and cervical cytology analysis was performed. HPV+ viral types were identified using PCR: HPV+ was observed in 14.7% of SLE, 27.9% of RA and 30.8% of controls. High-risk HPV types were observed in 11.7% of women with SLE, 27.9% of women with RA, and in 26% of the controls. High-risk viral types 58, 35 and 18 were the most frequently identified in SLE. Two women with SLE had a high-grade squamous intraepithelial lesion and one had cervical cancer. An association was observed between methotrexate utilization, longer duration of therapy with prednisone, and HPV+ in RA or SLE. Thus, there is a high prevalence of cervical HPV infection in Mexican women with SLE or RA, and physicians must be vigilant in preventing the development of cervical dysplasia.
To assess the awareness and training of primary care physicians on nutrition in older patients.
Observational, real-world data survey.
Primary Care.
One hundred sixty-two physicians, generalists and ...specialists, working in primary care.
Participants received an online questionnaire with 18 questions concerning the importance of nutrition, degree of knowledge, needs, and training in nutrition. The results were evaluated using univariate descriptive analysis, with a percentage for each chosen answer. Logistic regression models were used to evaluate if answers were related to training in nutrition and professional experience.
43.2% of participants reported that nutrition is very important in individuals over 65 years old, and 90% were aware of the importance of nutrition in healthy aging. Nutritional problems affect 30 to 50% of patients, according to 44.7% of participants. 89.2% agree about the need for nutritional assessment in older patients; however, the professionals believe they should be better prepared. Two out of three respondents consider the training received in nutrition during their undergraduate course or continuing medical education as deficient. Time of professional practice was mainly associated with conceptual facts, while continuing medical education did with practical issues, mainly the use of screening and diagnostic tools FRAIL (OR: 3.16; 95%IC: 1.55-6.46), MNA-SF (OR: 6.455; 95%IC: 2.980-13.981) and SARC-F (OR: 3.063; 95%IC: 1.284-7.309).
Although primary care professionals are aware of the importance of nutrition in older patients, there are still gaps in daily practice that could be improved by developing educational strategies.
The use of pesticides in agriculture has ensured the production of different crops. However, pesticides have become an emerging public health problem for Latin American countries due to their ...excessive use, inadequate application, toxic characteristics, and minimal residue control. The current project evaluates the ability of two strains of algae (Chlorella and Scenedesmus sp.) and one cyanobacteria (Hapalosyphon sp.) to remove excess pesticides and other nutrients present in runoff water from rice production. Different concentrations of wastewater and carbon sources (Na2CO3 and NaHCO3) were evaluated. According to the results, all three strains can be grown in wastewater without dilution (100%), with a biomass concentration comparable to a synthetic medium. All three strains significantly reduced the concentration of NO3 and PO4 (95 and 85%, respectively), with no difference between Na2CO3 or NaHCO3. Finally, Chlorella sp. obtained the highest removal efficiency of the pesticide (Chlorpyrifos), followed by Scenedesmus and Hapalosyphon sp. (100, 75, and 50%, respectively). This work shows that it is possible to use this type of waste as an alternative source of nutrients to obtain biomass and metabolites of interest, such as lipids and carbohydrates, to produce biofuels.
Among deuterostomes, the regenerative potential is maximally expressed in echinoderms, animals that can quickly replace most injured organs. In particular, sea cucumbers are excellent models for ...studying organ regeneration since they regenerate their digestive tract after evisceration. However, echinoderms have been sidelined in modern regeneration studies partially because of the lack of genome-wide profiling approaches afforded by modern genomic tools.For the last decade, our laboratory has been using the sea cucumber Holothuria glaberrima to dissect the cellular and molecular events that allow for such amazing regenerative processes. We have already established an EST database obtained from cDNA libraries of normal and regenerating intestine at two different regeneration stages. This database now has over 7000 sequences.
In the present work we used a custom-made microchip from Agilent with 60-mer probes for these ESTs, to determine the gene expression profile during intestinal regeneration. Here we compared the expression profile of animals at three different intestinal regeneration stages (3-, 7- and 14-days post evisceration) against the profile from normal (uneviscerated) intestines. The number of differentially expressed probes ranged from 70% at p < 0.05 to 39% at p < 0.001. Clustering analyses show specific profiles of expression for early (first week) and late (second week) regeneration stages. We used semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) to validate the expression profile of fifteen microarray detected differentially expressed genes which resulted in over 86% concordance between both techniques. Most of the differentially expressed ESTs showed no clear similarity to sequences in the databases and might represent novel genes associated with regeneration. However, other ESTs were similar to genes known to be involved in regeneration-related processes, wound healing, cell proliferation, differentiation, morphological plasticity, cell survival, stress response, immune challenge, and neoplastic transformation. Among those that have been validated, cytoskeletal genes, such as actins, and developmental genes, such as Wnt and Hox genes, show interesting expression profiles during regeneration.
Our findings set the base for future studies into the molecular basis of intestinal regeneration. Moreover, it advances the use of echinoderms in regenerative biology, animals that because of their amazing properties and their key evolutionary position, might provide important clues to the genetic basis of regenerative processes.
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