RESUMEN
The synthesis of mixed ligand di-n-butyltin complexes, [(n-Bu2SnL1-3)2SO4], 2-4 (HL1-3=2-quinoline/ 1-isoquinoline/ 4-methoxy-2-quinoline carboxylic acid) has been realized by reacting n-Bu2Sn(OMe)OSO2Me, 1 a with the corresponding quinaldic acid under solvothermal conditions. The observed transformation of methane sulfonate to sulfate anion represents a rare example of C-S bond cleavage on the organotin scaffolds, n-Bu2Sn(L1-3)OSO2Me, which have been identified as en route intermediates by NMR and X-ray crystallography. Analogous reaction when extended with Me2Sn(OMe)OSO2Me, 1 b and HL2 yields [(Me2Sn)2(L2)3(OSO2Me)], 5 as partially disproportionated product of Me2Sn(L2)OSO2Me. The solid-state structures of 2-5 reveal variable modes of coordination of the ligands to afford molecular and polymeric motifs.
RESUMEN
Synthetic cosmetics, particularly hair dyes, are becoming increasingly popular among people of all ages and genders. 2,4,5,6-tetraaminopyrimidine sulfate (TAPS) is a key component of oxidative hair dyes and is used as a developer in several hair dyes. TAPS has previously been shown to absorb UVB strongly and degrade in a time-dependent manner, causing phototoxicity in human skin cells. However, the toxic effects of UVB-degraded TAPS are not explored in comparison to parent TAPS. Therefore, this research work aims to assess the toxicity of UVB-degraded TAPS than TAPS on two different test systems, that is, HaCaT (mammalian cell) and Staphylococcus aureus (a bacterial cell). Our result on HaCaT has illustrated that UVB-degraded TAPS is less toxic than parent TAPS. Additionally, UVB-exposed TAPS and parent TAPS were given to S. aureus, and the bacterial growth and their metabolic activity were assessed via CFU and phenotype microarray. The findings demonstrated that parent TAPS reduced bacterial growth via decreased metabolic activity; however, bacteria easily utilized the degraded TAPS. Thus, this study suggests that the products generated after UVB irradiation of TAPS is considered to be safer than their parent TAPS.
Asunto(s)
Tinturas para el Cabello , Femenino , Masculino , Animales , Humanos , Tinturas para el Cabello/toxicidad , Tinturas para el Cabello/metabolismo , Sulfatos/toxicidad , Staphylococcus aureus , Piel , Cabello , Rayos Ultravioleta/efectos adversos , Queratinocitos/metabolismo , MamíferosRESUMEN
Recently, there has been considerable interest in the functions of gut microbiota in broiler chickens in relation to their use as feed additives. However, the gut-microbiota of chickens reared at different altitudes are not well documented for their potential role in adapting to prevailing conditions and functional changes. In this context, the present study investigates the functional diversity of gut-microbes in high-altitude (HACh) and low-altitude adapted chickens (LACh), assessing their substrate utilization profile through Biolog Ecoplates technology. This will help in the identification of potential microbes or their synthesized metabolites, which could be beneficial for the host or industrial applications. Results revealed that among the 31 different types of studied substrates, only polymers, carbohydrates, carboxylic acids, and amine-based substrates utilization varied significantly (p < 0.05) among the chickens reared at two different altitudes where gut-microbes of LACh utilized a broad range of substrates than the HACh. Further, diversity indices (Shannon and MacIntosh) analysis in LACh samples showed significant (p < 0.05) higher richness and evenness of microbes as compared to the HACh samples. However, no significant difference was observed in the Simpson diversity index in gut microbes of lowversus high-altitude chickens. In addition, the Principal Component Analysis elucidated variation in substrate preferences of gut-microbes, where 13 and 8 carbon substrates were found to constitute PC1 and PC2, respectively, where γ-aminobutyric acid, D-glucosaminic acid, i-erythritol and tween 40 were the most relevant substrates that had a major effect on PC1, however, alpha-ketobutyric acid and glycyl-L-glutamic acid affected PC2. Hence, this study concludes that the gut-microbes of high and low-altitudes adapted chickens use different carbon substrates so that they could play a vital role in the health and immunity of an animal host based on their geographical location. Consequently, this study substantiates the difference in the substrate utilization and functional diversity of the microbial flora in chickens reared at high and low altitudes due to altitudinal changes.
Asunto(s)
Altitud , Microbioma Gastrointestinal , Animales , Pollos , Ácido Glutámico , Carbono/análisisRESUMEN
The modified solvent removal method was used to encapsulate metformin hydrochloride (MH) within poly(lactic-co-glycolic acid) (PLGA) microspheres. The study investigated the effect of varying polymer concentrations on the loading and release of the drug from the microspheres. The encapsulation process involved using a double emulsion method, resulting in microspheres with particle diameters ranging from approximately 4.4µm to 2.7µm. The study achieved high encapsulation efficiencies, ranging from 81% to 90%, with drug loadings ranging from 18% to 11%. The release of the drug from the microspheres followed a biphasic pattern over 24 days, with nearly complete release by the end of the study period. Fourier transform infrared spectroscopy (FTIR) analysis indicated that there were no notable differences between PLGA and MH-loaded microspheres, suggesting minimal interactions between MH and PLGA. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques were used to investigate the state of the MH within the microspheres. The results suggested that the MH was dispersed at a molecular level within the spheres and existed in an amorphous state. This amorphous state of the drug may explain the slow and prolonged release observed in the study.
RESUMEN
This study was undertaken to investigate the role of CD4+FoxP3+ regulatory T cells (Tregs) in regulating neuroinflammation during viral Ag-challenge and re-challenge. CD8+ lymphocytes persisting within tissues are designated tissue-resident memory T cells (TRM), within brain: bTRM. Reactivation of bTRM with T cell epitope peptides generates rapid antiviral recall, but repeated stimulation leads to cumulative dysregulation of microglial activation, proliferation, and prolonged neurotoxic mediator production. Here, we show Tregs were recruited into murine brains following prime-CNS boost, but displayed altered phenotypes following repeated Ag-challenge. In response to repeated Ag, brain Tregs (bTregs) displayed inefficient immunosuppressive capacity, along with reduced expression of suppression of tumorigenicity 2 (ST2) and amphiregulin (Areg). Ex vivo Areg treatment revealed reduced production of neurotoxic mediators such as iNOS, IL-6, and IL-1ß, and decreased microglial activation and proliferation. Taken together, these data indicate bTregs display an unstable phenotype and fail to control reactive gliosis in response to repeated Ag-challenge.
RESUMEN
An in-depth study of the class of organotin cations bearing weakly coordinating trifluoromethanesulfonate/arylsulfonate has led to key insights into their stability, structural aspects, and role as catalysts. Related chemistry with alkanesulfonate ligands remains a missing link due to the strong Sn-O bond. The study reported herein describes the scope of diorganostannates, [n-Bu4N][R2Sn(OSO2R1)3] (R = n-Bu, R1 = Me(1), Et(2); R = Ph, R1 = Me(3)), as reactive substrates in the presence of adventitious water to afford [n-Bu2SnOH(OSO2Me)] (4), [n-Bu2Sn(H2O)4][n-Bu4N][OSO2Et]3·H2O (5), and [Ph2Sn(H2O)4][n-Bu4N]2[OSO2Me]4 (6), respectively, the latter two being the first examples of salt cocrystals comprising tetra(aqua)diorganotin cations. Hydrolysis of 3 in the presence of 1,4-bis((1H-imidazol-1-yl)methyl)benzene (bix) as the N-donor ligand proceeds via disproportionation and yields [Ph3Sn(bix)](OSO2Me) (7) along with an insoluble solid, likely derived from the hydrolysis of PhSn(OSO2Me)3. Direct evidence of this phenomenon can be gleaned from ESI-MS of 3, which identifies mass clusters corresponding to [Ph3Sn(OSO2Me)2]- and [PhSn(OSO2Me)3-H+]-. X-ray crystallographic studies of 1-7 are reported to establish their structural identity and the role of alkanesulfonate anions in the formation of supramolecular assemblies.
RESUMEN
Background: Immune dysregulation plays a key role in determining COVID-19 disease severity. We aimed to analyze the T cell activation profile in COVID - 19 cases and its predictive role in disease severity and outcome. Material & methods: This was a prospective observational pilot study from a tertiary care COVID-19 hospital. Peripheral blood samples obtained between the fifth and seventh day of COVID-19 illness, were subjected to lymphocyte subset analysis using multicolor flowcytometry using a single tube, 8 antibodies (CD45, CD19, CD3, CD4, CD8, CD38, HLADR, and CD56) analysis. Correlation between lymphocyte subset analysis and clinical profile was determined. Results: 26 patients including 11 with mild disease and 15 with severe disease were enrolled. The median age was 58 years (range: 33-81), with a male: female ratio of 1.36:1. Significant lymphopenia was observed in the severe group compared to the mild group (p < 0.02). The absolute numbers of CD3+, CD4+, CD8 + T cells, B cells, and NK cells were significantly reduced in the severe group as compared to the mild group (p < 0.05). In patients with severe disease, the proportion of CD8 + and CD4 + T cells were significantly higher than those in patients with mild disease (p = 0.0372). Using ROC analysis, a CD4:8 T cell ratio of ≥ 2.63 and an activated (CD38 + HLA-DR+) CD8 T cell proportion of > 15.85% of the total CD8 T cell population, significantly determined the severe disease category. Conclusions: Severe COVID-19 is associated with severe lymphopenia, altered CD4/CD8 ratio and markedly increased CD8 T cell activation profile. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01558-6.
RESUMEN
Cytochrome bd-I from Escherichia coli is a terminal oxidase in the respiratory chain that plays an important role under stress conditions. Cytochrome bd-I was thought to consist of the major subunits CydA and CydB plus the small CydX subunit. Recent high-resolution structures of cytochrome bd-I demonstrated the presence of an additional subunit, CydH/CydY (called CydH here), the function of which is unclear. In this report, we show that in the absence of CydH, cytochrome bd-I is catalytically active, can sustain bacterial growth and displays haem spectra and susceptibility for haem-binding inhibitors comparable to the wild-type enzyme. Removal of CydH did not elicit catalase activity of cytochrome bd-I in our experimental system. Taken together, in the absence of the CydH subunit cytochrome bd-I retained key enzymatic properties.
Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Grupo Citocromo b/genética , Grupo Citocromo b/química , Citocromos/genética , Citocromos/química , Proteínas del Complejo de Cadena de Transporte de Electrón/genética , Proteínas del Complejo de Cadena de Transporte de Electrón/química , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , HemoRESUMEN
The extensive utilization of nanoparticles in cancer therapies has inspired a new field of study called cancer nanomedicine. In contrast to traditional anticancer medications, nanomedicines offer a targeted strategy that eliminates side effects and has high efficacy. With its vast surface area, variable pore size, high pore volume, abundant surface chemistry and specific binding affinity, mesoporous silica nanoparticles (MPSNPs) are a potential candidate for cancer diagnosis and treatment. However, there are several bottlenecks associated with nanoparticles, including specific toxicity or affinity towards particular body fluid, which can cater by architecting core-shell nanosystems. The core-shell chemistries, synergistic effects, and interfacial heterojunctions in core-shell nanosystems enhance their stability, catalytic and physicochemical attributes, which possess high performance in cancer therapeutics. This review article summarizes research and development dedicated to engineering mesoporous core-shell nanosystems, especially silica nanoparticles and Fe3O4@Au nanoparticles, owing to their unique physicochemical characteristics. Moreover, it highlights state-of-the-art magnetic and optical attributes of Fe3O4@Au and MPSNP-based cancer therapy strategies. It details the designing of Fe3O4@Au and MPSN to bind with drugs, receptors, ligands, and destroy tumour cells and targeted drug delivery. This review serves as a fundamental comprehensive structure to guide future research towards prospects of core-shell nanosystems based on Fe3O4@Au and MPSNP for cancer theranostics.
RESUMEN
Tuberculosis is recognized as one of the major public health threats worldwide. The DevR-DevS (DosR/DosS) two-component system is considered a novel drug target in Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, owing to its central role in bacterial adaptation and long-term persistence. An increase in DevR levels and the decreased permeability of the mycobacterial cell wall during hypoxia-associated dormancy pose formidable challenges to the development of anti-DevR compounds. Using an in vitro evolution approach of Systematic Evolution of Ligands by EXponential enrichment (SELEX), we developed a panel of single-stranded DNA aptamers that interacted with Mtb DevR protein in solid-phase binding assays. The best-performing aptamer, APT-6, forms a G-quadruplex structure and inhibits DevR-dependent transcription in Mycobacterium smegmatis. Mechanistic studies indicate that APT-6 functions by inhibiting the dimerization and DNA binding activity of DevR protein. In silico studies reveal that APT-6 interacts majorly with C-terminal domain residues that participate in DNA binding and formation of active dimer species of DevR. To the best of our knowledge, this is the first report of a DNA aptamer that inhibits the function of a cytosolic bacterial response regulator. By inhibiting the dimerization of DevR, APT-6 targets an essential step in the DevR activation mechanism, and therefore, it has the potential to universally block the expression of DevR-regulated genes for intercepting dormancy pathways in mycobacteria. These findings also pave the way for exploring aptamer-based approaches to design and develop potent inhibitors against intracellular proteins of various bacterial pathogens of global concern.
Asunto(s)
Aptámeros de Nucleótidos , Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Aptámeros de Nucleótidos/farmacología , ADNRESUMEN
Microbial populations often contain persister cells, which reduce the extinction risk upon sudden stresses. Persister cell formation is deeply intertwined with physiology. Due to this complexity, it cannot be satisfactorily understood by focusing only on mechanistic, physiological or evolutionary aspects. In this review, we take an integrative biology perspective to identify common principles of persister cell formation, which might be applicable across evolutionary-distinct microbes. Persister cells probably evolved to cope with a fundamental trade-off between cellular stress and growth tasks, as any biosynthetic resource investment in growth-supporting proteins is at the expense of stress tasks and vice versa. Natural selection probably favours persister cell subpopulation formation over a single-phenotype strategy, where each cell is prepared for growth and stress to a suboptimal extent, since persister cells can withstand harsher environments and their coexistence with growing cells leads to a higher fitness. The formation of coexisting phenotypes requires bistable molecular circuitry. Bistability probably emerges from growth-modulated, positive feedback loops in the cell's growth versus stress control network, involving interactions between sigma factors, guanosine pentaphosphate and toxin-antitoxin (TA) systems. We conclude that persister cell formation is most likely a response to a sudden reduction in growth rate, which can be achieved by antibiotic addition, nutrient starvation, sudden stresses, nutrient transitions or activation of a TA system.
Asunto(s)
Antibacterianos , Regulación Bacteriana de la Expresión Génica , Biología , FenotipoRESUMEN
Regulatory T-cells (Tregs) play pivotal roles during infection, cancer, and autoimmunity. In our previous study, we demonstrated a role for the PD-1:PD-L1 pathway in controlling cytolytic responses of CD8+ T lymphocytes against microglial cells presenting viral peptides. In this study, we investigated the role of Tregs in suppressing CD8+ T-cell-mediated cytotoxicity against primary microglial cells. Using in vitro cytotoxicity assays and flow cytometry, we demonstrated a role for Tregs in suppressing antigen-specific cytotoxic T-lymphocyte (CTL) responses against microglia loaded with a model peptide (SIINFEKL). We went on to show a significant decrease in the frequency of IFN-γ- and TNF-producing CD8+ T-cells when cultured with Tregs. Interestingly, a significant increase in the frequency of granzyme B- and Ki67-producing CTLs was observed. We also observed a significant decrease in the production of interleukin (IL)-6 by microglia. On further investigation, we found that Tregs significantly reduced MHC class 1 (MHC-1) expression on IFN-γ-treated microglial cells. Taken together, these studies demonstrate an immunosuppressive role for Tregs on CTL responses generated against primary microglia. Hence, modulation of Treg cell activity in combination with negative immune checkpoint blockade may stimulate anti-viral T-cell responses to more efficiently clear viral infection from microglial cell reservoirs.
Asunto(s)
Linfocitos T Citotóxicos , Linfocitos T Reguladores , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , Granzimas/metabolismo , Inhibidores de Puntos de Control Inmunológico , Interferón gamma/metabolismo , Interleucinas/metabolismo , Antígeno Ki-67/metabolismo , Microglía/metabolismo , Receptor de Muerte Celular Programada 1/metabolismoRESUMEN
For the design of next-generation tuberculosis chemotherapy, insight into bacterial defence against drugs is required. Currently, targeting respiration has attracted strong attention for combatting drug-resistant mycobacteria. Q203 (telacebec), an inhibitor of the cytochrome bcc complex in the mycobacterial respiratory chain, is currently evaluated in phase-2 clinical trials. Q203 has bacteriostatic activity against M. tuberculosis, which can be converted to bactericidal activity by concurrently inhibiting an alternative branch of the mycobacterial respiratory chain, cytochrome bd. In contrast, non-tuberculous mycobacteria, such as Mycobacterium smegmatis, show only very little sensitivity to Q203. In this report, we investigated factors that M. smegmatis employs to adapt to Q203 in the presence or absence of a functional cytochrome bd, especially regarding its terminal oxidases. In the presence of a functional cytochrome bd, M. smegmatis responds to Q203 by increasing the expression of cytochrome bcc as well as of cytochrome bd, whereas a M. smegmatisbd-KO strain adapted to Q203 by increasing the expression of cytochrome bcc. Interestingly, single-cell studies revealed cell-to-cell variability in drug adaptation. We also investigated the role of a putative second cytochrome bd isoform postulated for M. smegmatis. Although this putative isoform showed differential expression in response to Q203 in the M. smegmatisbd-KO strain, it did not display functional features similar to the characterised cytochrome bd variant.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Citocromos/metabolismo , Humanos , Imidazoles , Mycobacterium smegmatis , Mycobacterium tuberculosis/metabolismo , Oxidorreductasas/metabolismo , Piperidinas , Piridinas , Tuberculosis/tratamiento farmacológicoRESUMEN
Herein, Bacillus subtilis PBE-8's biocontrol efficacy was evaluated through physiological and metabolic approaches against Fusarium oxysporum f.sp. lycopersici (FOL). The study elaborates on PBE-8's cell-free filtrate (CFF) antifungal activity through mycelial growth inhibition, metabolite profiling, and substrates utilization patterns. Additionally, under different CFF concentrations, reduction in spore count (94%-55%), biomass (50%), and cytoplasmic bulbous protrusions in mycelia were also observed. Furthermore, the effect of bacterial CFF on FOL metabolism was confirmed through GC-MS. CFF suppresses the concentration of aliphatic amino acids like L-valine, L-leucine, L-Isoleucine, glycine, and fatty acids such as linoleic acid and α- linolenic acid during the co-culturing conditions, which are essential for pathogenicity and resistance against host's systemic acquired resistance. The phenotype microarray assay revealed that CFF-treated FOL shows phenotype loss in 507 (56.58%) out of 896 substrates. Among 507, twenty-seven substrates showed significant phenotype loss, among which four substrates such as L-glutamic acid, L-glutamine, ammonia, and L-arginine are common in different crucial metabolic pathways of FOL, like alanine, aspartate, and glutamate metabolism, arginine and proline, carbon metabolism, arginine biosynthesis, nitrogen metabolism, amino-acyl tRNA synthesis, and biosynthesis of amino acids. The results suggest that PBE-8 CFF has certain antifungal metabolites that hinder the fungal metabolic pathways.
Asunto(s)
Fusarium , Solanum lycopersicum , Alanina/genética , Alanina/farmacología , Amoníaco , Antifúngicos/farmacología , Arginina , Ácido Aspártico , Bacillus subtilis/genética , Biotransformación , Carbono , Fusarium/genética , Ácido Glutámico/genética , Ácido Glutámico/farmacología , Glutamina/genética , Glutamina/farmacología , Glicina , Isoleucina/genética , Isoleucina/farmacología , Leucina/genética , Leucina/farmacología , Ácidos Linoleicos/farmacología , Ácidos Linolénicos/farmacología , Solanum lycopersicum/microbiología , Análisis por Micromatrices , Nitrógeno , Fenotipo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Prolina/genética , Prolina/farmacología , ARN de Transferencia/farmacología , Valina/genética , Valina/farmacologíaRESUMEN
The study describes the synthesis and structural attributes of two new cadmium phosphites, [Cd{OP(O)(OH)H}2(4,4'-bipy)] (1) and [H2pip][Cd(HPO3)2(H2O)]·H2O (2). The structure of 1 adopts a two-dimensional motif featuring alternate [Cd-µ2-O]2 and [Cd-O-P-O]2-cyclic rings, while the inorganic chains are held together by 4,4'-bipyridine. The presence of strong hydrogen bonding interactions between the appended H2PO3 groups (O---O = 2.55 Å) provides a facile proton conduction pathway and results in a proton conductivity of 3.2 × 10-3 S cm-1 at 75 °C under 77% relative humidity (RH). Compound 2 comprises an anionic framework formed by vertex-shared [Cd-O-P-O]2-cyclic rings, while the [H2pip] cations between the adjacent chains assist a well-directed O-H---O hydrogen-bonded network between coordinated water, lattice water, and phospite groups. The bulk proton conductivity value under conditions as in 1 reaches 4.3 × 10-1 S cm-1. For both 1 and 2, the proton conductivity remains practically unchanged under ambient temperatures (25-35 °C), suggesting their potential in low-temperature fuel cells.
RESUMEN
Endophytes can induce the defence responses and modulates physiological attributes in host plants during pathogen attacks. In the present study, 127 bacterial endophytes (BEs) were isolated from different parts of healthy soybean plant. Among them, two BEs (M-2 and M-4) resulted a significant antagonistic property against Macrophomina phaseolina, causes charcoal rot disease in soybean. The antagonistic potential was evaluated through dual culture plate assay, where M-4 expressed higher antifungal activity than M-2 against M. phaseolina. The M-4 produces cell wall degrading enzymes viz. cellulase (145.71 ± 1.34 µgmL-1), chitinase (0.168 ± 0.0009 unitmL-1) and ß,1-3 endoglucanase (162.14 ± 2.5 µgmL-1), which helps in cell wall disintegration of pathogens. Additionally, M-4 also can produce siderophores, indole-3-acetic acid (IAA) (17.03 ± 1.10 µgmL-1) and had a phosphate solubilization potential (19.89 ± 0.26 µgmL-1). Further, GC-MS profiling of M-4 has been carried out to demonstrate the production of lipophilic secondary metabolites which efficiently suppress the M. phaseolina defensive compounds under co-culture conditions. Bio-efficacy study of M-4 strain shown a significant reduction in disease incidence around 60 and 80% in resistant and susceptible varieties of soybean, respectively. The inoculation of M-4 potentially enhances the physiological attributes and triggers various defence responsive enzymes viz. superoxide dismutase (SOD), phenol peroxidase (PPO), peroxidase (PO) and catalase (CAT). The histopathological study also confirmed that M-4 can reduce the persistence of microsclerotia in root and shoot tissue. Conclusively, M-4 revealed as an efficient biocontrol agent that can uses multifaceted measures for charcoal rot disease management, by suppress the M. phaseolina infection and enhance the physiological attributes of soybean.
Asunto(s)
Celulasa , Glycine max , Ascomicetos , Bacillus subtilis , Peroxidasa , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Glycine max/microbiologíaRESUMEN
BACKGROUND: The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. METHODS: A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. RESULTS: A total of 137 AML patients (median age 32 year (3-66 years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45 days (6-177 days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91-15.08) and 15.0 ± 2.44 (95% CI 10.21-19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50-27.49) vs 9.0 (95% CI: 2.99-15.01) months; p = 0.002); time from diagnosis to treatment (< 30 days vs ≥ 30 days; not reached vs 9.0 (95% CI: 6.81-11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32-13.67) vs 4.0 (95% CI:2.77-5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78-8.21); p = 0.002). CONCLUSION: Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.
Asunto(s)
Infecciones por Bacterias Gramnegativas , Leucemia Mieloide Aguda , Sepsis , Adulto , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/epidemiología , Pronóstico , Inducción de Remisión , Estudios RetrospectivosAsunto(s)
Calreticulina , Mielofibrosis Primaria , Calreticulina/genética , Niño , Humanos , Mutación , Mielofibrosis Primaria/genéticaRESUMEN
There is limited evidence on various clinical aspects of SARS-CoV-2 infection in patients with haematological cancers. The risk factors, prognosis, and outcome of patients with haematological cancers with coexistent COVID-19 need to be explored in different subsets of population. A single-institutional prospective observational study was conducted at a tertiary level medical institute in North India. The clinical details of the recruited patients having haematological malignancies and diagnosed with COVID-19 between 15 March 2020 and 31 May 2021 were prospectively collected through the electronic patient database system. The outcomes with respect to 28-day and 56-day mortality and the associated risk factors for prognostication were analysed. Of the 5750 hospital admissions (inpatient and day-care) during the study period, two hundred and forty-two patients (4.2%) were diagnosed with COVID-19. Acute leukaemia was the most common haematological malignancy, seen in 117 (48.3%) patients. Eighty-nine (36.8%) patients had moderate-to-severe COVID-19 while 153 (63.2%) patients presented with mild infection. The 28-day and 56-day mortality rates in our cohort were 13.3% and 19.8% respectively. Amongst the risk factors associated with poor outcome, the severity of COVID-19 (HR = 1.8, 95% CI 1.16-10.35; p = 0.04), presence of secondary infection (HR = 2.1, 95% CI 2.45-21.3; p = 0.023), and need for invasive mechanical ventilation (HR = 2.3, 95% CI 1.8-18.43; p = 0.01) were prognostically significant on multivariate log rank analysis. The risk of SARS-CoV-2 infection does not increase with haematological malignancies; however, the outcome remains poor in patients with severe COVID-19, requirement of invasive mechanical ventilation, and pre-existing bacterial/fungal infection at presentation.