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INTRODUCTION: Previously, our institution measured peripheral blood CD34 cell counts both pre- and post-peripheral blood stem cell harvest (PBSCH), with both samples analyzed simultaneously post-PBSCH. Since 2021, we have measured pre-CD34 cell counts during PBSCH, adjusting the processed blood volume based on these results. We retrospectively evaluated how this change impacted cellular therapy. METHODS: Related healthy donors were included and divided into 1-day and 2-day harvest cohorts. Donors with CD34 cell counts measured post- and during PBSCH were categorized into the previous and current sub-cohorts, respectively. RESULTS: Regarding the 1-day cohort (n = 212), the current sub-cohort had a significantly shorter average harvest duration (151 [standard deviation, SD = 45.1] vs. 180 [SD = 27.8] minutes, respectively) and higher average infusion rates (87.6% [SD = 21.1] vs. 78.1% [SD = 25.7], respectively) than the previous sub-cohort. CONCLUSION: Adjusting the processed blood volume based on pre-PBSCH CD34 cell counts measured during the harvest may reduce donor burden and enhance workflow efficiency.
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Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.
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Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/mortalidade , Adulto , Estudos Retrospectivos , Prognóstico , Transplante de Células-Tronco Hematopoéticas , Receptores de Antígenos Quiméricos , RecidivaRESUMO
Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.
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Antígenos Virais , Proteínas do Capsídeo , Mutação , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Rotavirus/genética , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Camundongos , Infecções por Rotavirus/virologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/genética , Vacinas contra Rotavirus/imunologia , Vacinas contra Rotavirus/administração & dosagem , Humanos , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Camundongos Endogâmicos BALB C , Linhagem Celular , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vírion/genética , FemininoRESUMO
BACKGROUND: Phase angle (PhA), which is measured using bioelectrical impedance analysis, is an indicator of muscle quality and malnutrition. PhA has been shown to be correlated with sarcopenia and malnutrition; however, studies on patients with chronic obstructive pulmonary disease (COPD) are limited. In this study, we investigated the correlation between PhA and sarcopenia and malnutrition and determined the cutoff values of PhA for those in patients with COPD. METHODS: This study included 105 male patients with COPD (mean age 75.7 ± 7.7 years, mean forced expiratory volume in 1s % predicted [%FEV1] 57.0 ± 20.1%) and 12 male controls (mean age 74.1 ± 3.8 years) who were outpatients between December 2019 and March 2024. PhA was measured using the InBody S10, and its correlation with sarcopenia and malnutrition was assessed. The cutoff PhA values for sarcopenia and malnutrition were determined using receiver operating characteristic curves. RESULTS: The prevalence rates of sarcopenia and malnutrition were 31% and 22%, respectively, in patients with COPD. PhA significantly correlated with sarcopenia- and malnutrition-related indicators. Multivariate logistic regression analysis independently correlated PhA with sarcopenia and malnutrition. The cutoff values of the PhA for sarcopenia and malnutrition were 4.75° (AUC = 0.78, 95% CI = 0.68-0.88) and 4.25° (AUC = 0.75, 95% CI = 0.63-0.86), respectively. CONCLUSIONS: PhA was significantly correlated with sarcopenia and malnutrition in Japanese patients with COPD and may be a useful diagnostic indicator.
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Impedância Elétrica , Desnutrição , Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Humanos , Sarcopenia/epidemiologia , Sarcopenia/etiologia , Sarcopenia/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Desnutrição/etiologia , Masculino , Idoso , Prevalência , Idoso de 80 Anos ou mais , Volume Expiratório ForçadoRESUMO
Disease recurrence remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Post-transplant maintenance therapy with azacitidine (AZA) is promising to prevent relapse but the outcomes are unsatisfactory in patients at high risk of recurrence. Herein, we evaluated the outcome in patients who received AZA and gemtuzumab ozogamicin (GO), anti-CD33 antibody-calicheamicin conjugate, as post-transplant maintenance therapy. Twenty-eight patients with high-risk hematologic malignancies harboring CD33-positive leukemic blasts received the maintenance therapy. AZA (30 mg/m2) was administered for 7 days, followed by GO (3 mg/m2) on day 8. The maximum number of cycles was 4. At transplant, 21 patients (75.0%) had active disease. Their 2-year overall survival, disease-free survival, relapse, and non-relapse mortality rates were 53.6%, 39.3%, 50.0%, and 10.7%, respectively. Of these patients, those with minimal residual disease at the start of maintenance therapy (n = 9) had a higher recurrence rate (66.7% vs. 42.1% at 2 years, P = 0.069) and shorter disease-free survival (11.1% vs. 52.6% at 2 years, P = 0.003). Post-transplant maintenance therapy with AZA and GO was generally tolerable but more than half of the patients eventually relapsed. Further improvements are needed to prevent relapse after transplantation in patients with high-risk hematologic malignancies.
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Azacitidina , Gemtuzumab , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Gemtuzumab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Azacitidina/uso terapêutico , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidade , Idoso , Aminoglicosídeos/uso terapêutico , Aminoglicosídeos/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
A 28-year-old man was diagnosed with acute myelomonocytic leukemia. He achieved complete remission (CR) after two cycles of induction therapy. However, after consolidation therapy, bone marrow aspiration performed to prepare for allogeneic hematopoietic stem cell transplantation revealed disease relapse. Companion diagnostics confirmed the presence of the FLT3-ITD mutation. The patient received gilteritinib monotherapy and achieved CR. Subsequently, he underwent unrelated allogeneic bone marrow transplantation. One year after transplantation, the patient relapsed, and gilteritinib was resumed. However, the leukemia progressed, and panel sequencing using a next-generation sequencer showed that the FLT3-ITD mutation disappeared. A mutation in PTPN11, which regulates the RAS/MAPK signaling pathway, was also detected. Gilteritinib was discontinued, and the patient achieved CR with salvage chemotherapy. He underwent related haploidentical peripheral blood stem cell transplantation but died of relapse. This was a case in which genetic analysis revealed clonal transition and acquisition of resistance to treatment.
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Leucemia Mieloide Aguda , Masculino , Humanos , Adulto , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Compostos de Anilina , Pirazinas , Doença Crônica , Mutação , Resposta Patológica Completa , Tirosina Quinase 3 Semelhante a fms/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genéticaRESUMO
A 63-year-old man with adult T-cell leukemia-lymphoma underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor. On day 17 after transplantation, chest computed tomography (CT) showed nodules in the lower lobes of both lungs, and invasive pulmonary aspergillosis (IPA) was suspected. Treatment with liposomal amphotericin B was started, and improvement of infectious lesions was confirmed with CT on day 28. The antifungal agent was changed to voriconazole on day 52 because of progressive renal dysfunction. Disorders of consciousness and paralysis of the left upper and lower extremities developed on day 61. Brain CT showed subcortical hemorrhage in the right parietal and occipital lobes, and the patient died on day 62. An autopsy revealed filamentous fungi, suspected to be Aspergillus, in the pulmonary nodules and a ruptured cerebral aneurysm. Although IPA occurs in 10% of transplant recipients, vigilant monitoring for mycotic cerebral aneurysms is required to prevent hematogenous dissemination of Aspergillus, which is associated with a high mortality rate.
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Transplante de Células-Tronco Hematopoéticas , Aneurisma Intracraniano , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/terapia , Transplante de Medula ÓsseaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes several host proteases to cleave the spike (S) protein to enter host cells. SARS-CoV-2 S protein is cleaved into S1 and S2 subunits by furin, which is closely involved in the pathogenicity of SARS-CoV-2. However, the effects of the modulated protease cleavage activity due to S protein mutations on viral replication and pathogenesis remain unclear. Herein, we serially passaged two SARS-CoV-2 strains in Vero cells and characterized the cell-adapted SARS-CoV-2 strains in vitro and in vivo. The adapted strains showed high viral growth, effective S1/S2 cleavage of the S protein, and low pathogenicity compared with the wild-type strain. Furthermore, the viral growth and S1/S2 cleavage were enhanced by the combination of the Δ68-76 and H655Y mutations using recombinant SARS-CoV-2 strains generated by the circular polymerase extension reaction. The recombinant SARS-CoV-2 strain, which contained the mutation of the adapted strain, showed increased susceptibility to the furin inhibitor, suggesting that the adapted SARS-CoV-2 strain utilized furin more effectively than the wild-type strain. Pathogenicity was attenuated by infection with effectively cleaved recombinant SARS-CoV-2 strains, suggesting that the excessive cleavage of the S proteins decreases virulence. Finally, the high-growth-adapted SARS-CoV-2 strain could be used as the seed for a low-cost inactivated vaccine; immunization with this vaccine can effectively protect the host from SARS-CoV-2 variants. Our findings provide novel insights into the growth and pathogenicity of SARS-CoV-2 in the evolution of cell-cell transmission. IMPORTANCE: The efficacy of the S protein cleavage generally differs among the SARS-CoV-2 variants, resulting in distinct viral characteristics. The relationship between a mutation and the entry of SARS-CoV-2 into host cells remains unclear. In this study, we analyzed the sequence of high-growth Vero cell-adapted SARS-CoV-2 and factors determining the enhancement of the growth of the adapted virus and confirmed the characteristics of the adapted strain by analyzing the recombinant SARS-CoV-2 strain. We successfully identified mutations Δ68-76 and H655Y, which enhance viral growth and the S protein cleavage by furin. Using recombinant viruses enabled us to conduct a virus challenge experiment in vivo. The pathogenicity of SARS-CoV-2 introduced with the mutations Δ68-76, H655Y, P812L, and Q853L was attenuated in hamsters, indicating the possibility of the attenuation of excessive cleaved SARS-CoV-2. These findings provide novel insights into the infectivity and pathogenesis of SARS-CoV-2 strains, thereby significantly contributing to the field of virology.
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COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Animais , Chlorocebus aethiops , Humanos , Células Vero , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Furina/metabolismoRESUMO
An 18-year-old man underwent allogenic bone marrow transplantation (BMT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Ph+ALL relapsed 3 months after the first BMT, and the patient underwent a second BMT. However, Ph+ALL relapsed 4 months after the second BMT, and he received a haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) from his father. Molecular complete remission was confirmed 29 days after haplo-PBSCT. However, the patient needed dialysis for end-stage renal disease due to thrombotic microangiopathy 3 years and 2 months after haplo-PBSCT. He received a kidney transplantation from his father 7 years and 10 months after haplo-PBSCT, and got off dialysis after the kidney transplantation. Immunosuppressive therapy with methylprednisolone, tacrolimus, and mycophenolate mofetil was started for kidney transplantation, but the dose of immunosuppressive agents was reduced successfully without rejection soon after kidney transplantation. The patient has maintained long-term remission since the haplo-PBSCT, and his kidney function was restored by the kidney transplantation from his father.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Falência Renal Crônica , Transplante de Rim , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Humanos , Adolescente , Cromossomo Filadélfia , Transplante Homólogo , Transplante de Medula Óssea , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
The Egyptian Rousettus bat (Rousettus aegyptiacus) is a common fruit bat species that is distributed mainly in Africa and the Middle East. Bats serve as reservoir hosts for numerous pathogens. Human activities, such as hunting bats for food, managing vermin, and causing habitat loss, elevate the likelihood of transmission of bat pathogens to humans and other animals. Consequently, bat cell lines play a crucial role as research materials for investigating viral pathogens. However, the inherent limitation of finite cell division in primary cells necessitates the use of immortalized cells derived from various bat tissues. Herein, we successfully established six fibroblast cell lines derived from an infant bat heart and lungs and an elderly bat heart. Three of the six cell lines, called K4DT cells, were transduced by a combination of cell cycle regulators, mutant cyclin-dependent kinase 4, cyclin D1, and human telomerase reverse transcriptase. The other three cell lines, named SV40 cells, were transfected with simian virus 40 large T antigen. Transgene protein expression was detected in the transduced cells. All three K4DT cell lines and one lung-derived SV40 cell line were virtually immortalized and nearly maintained the normal diploid karyotypes. However, the two other heart-derived SV40 cell lines had aberrant karyotypes and the young bat-derived cell line stopped proliferating at approximately 40 population doublings. These bat cell lines are valuable for studying pathogen genomics and biology.
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Quirópteros , Animais , Humanos , Idoso , Egito , Linhagem CelularRESUMO
OBJECTIVES: Phase angle (PhA) reflects cell membrane integrity and vitality and is an indicator of sarcopenia. PhA is associated with physical function in patients with stable chronic obstructive pulmonary disease (COPD). To our knowledge, the association between PhA and physical activity (PA) has not been investigated. Therefore, the aim of this study was to investigate whether PhA reflects PA in patients with COPD. METHODS: This single-center, cross-sectional, observational study included 103 patients with stable COPD (87 men; mean age, 74.7 ± 8.1 y; mean forced expiratory volume in 1s %predicted value, 58.9 ± 20.4%). PhA was measured by bioelectrical impedance analysis. Patients were stratified into low (n = 54) and high (n = 49) PhA groups based on median values (4.3° ± 0.6° and 5.4° ± 0.5°, respectively). PA was calculated as the average daily duration of high-intensity light PA (HLPA; 2.0-2.9 metabolic equivalents [METs] of PA) and moderate- to vigorous-intensity PA (MVPA; >3 METs). Correlation and multivariate analyses using multiple regression analysis were performed to confirm the association between PhA and PA. RESULTS: The high-PhA group demonstrated greater HLPA (104.4 [16.5-332.5] versus 131.3 [61.1-328.7] min, P = 0.005) and MVPA (19.5 [4.7-96.0] versus 46.6 [8.9-139.3] min, P < 0.001) than the low-PhA group. PhA was positively correlated with HLPA (r = 0.32, P < 0.001) and MVPA (r = 0.49, P < 0.001). MVPA (ß = 0.178, P = 0.029) and HLPA (ß = 0.158, P = 0.026) were associated with PhA independent of age, sex, body mass index, respiratory function, muscle strength, skeletal muscle mass index, and 6-min walking distance. CONCLUSION: In patients with COPD, PhA may reflect PA as well as muscle function.
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Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Estudos Transversais , Impedância Elétrica , Exercício Físico , Força Muscular/fisiologia , Sarcopenia/etiologia , FemininoRESUMO
The outcomes of unresectable gastric cancer (GC) are unfavorable even with chemotherapy; therefore, a new treatment modality is required. The combination of an oncolytic virus and photodynamic therapy can be one of the promising modalities to overcome this. Mammalian orthoreovirus (MRV) is an oncolytic virus that has been used in clinical trials for several cancers. In this study, we developed and evaluated a recombinant MRV strain type 3 Dearing (T3D) that expresses membrane-targeting KillerRed (KRmem), a phototoxic fluorescent protein that produces cytotoxic reactive oxygen species upon light irradiation. KRmem was fused in-frame to the 3' end of the σ2 viral gene in the S2 segment using a 2A peptide linker, enabling the expression of multiple proteins from a single transcript. RNA electrophoresis, Western blotting, and immunofluorescence analyses confirmed functional insertion of KRmem into the recombinant virus. The growth activity of the recombinant virus was comparable to that of the wild-type MRV in a cultured cell line. The recombinant virus infected two GC cell lines (MKN45P and MKN7), and a significant cytocidal effect was observed in MKN45P cells infected with the recombinant virus after light irradiation. Thus, recombinant MRV-expressing KRmem has the potential to serve as a novel treatment tool for GC.
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This study aims to represent fine texture differences in pencil hardness using intensity segment modulation (ISM), a sensory equivalent conversion method of vibration from high to low frequencies. This method enables the presentation of delicate tactile sensations even with small transducers. We integrated this approach in the world's thinnest ultra-thin PZT-MEMS vibrator with a stylus-type device. The vibration waveforms of four types of pencil hardness were captured under the same conditions, and the differences in the frequency components were confirmed. We compared the fine texture feelings under raw signal, ISM, and ISM below 1 kHz conditions by conducting discrimination tests and subjective similarity evaluations. The results showed that ISM could reproduce similar feelings of the pencil hardness.
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Sistemas Microeletromecânicos , Percepção do Tato , Humanos , Dureza , Tato , VibraçãoRESUMO
Thin and light vibrators that leverage the inverse piezoelectric effect with a diaphragm mechanism are promising vibrotactile actuators owing to their form factors and high temporal and frequency response. However, generating perceptually sufficient displacement in the low-frequency domain is challenging. This study presents a lever mechanism mounted on a diaphragm vibrator to enhance the vibrotactile intensity of low-frequency vibrotactile stimuli. The lever mechanism is inspired by the tactile contact lens consisting of an array of cylinders held against the skin on a sheet that enhances micro-bump tactile detection. We built an experimental apparatus including our previously developed thin-film diaphragm-type vibrator, which reproduced the common characteristic of piezoelectric vibrators: near-threshold displacement (10 to 20 µm) at low frequency. Experiments demonstrated enhanced vibrotactile intensity at frequencies less than 100 Hz with the lever mechanism. Although the arrangement and material of the mechanism can be improved, our findings can help improve the expressiveness of diaphragm-type vibrators.
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Percepção do Tato , Humanos , Diafragma , Tato/fisiologia , Pele , VibraçãoRESUMO
Several recent studies have demonstrated that urinary levels of liver-type fatty acid-binding protein (L-FABP) can be used to stratify the prognosis of cardiac disease, cardiac intensive care unit admission, cirrhosis, and coronavirus disease 2019. Our initial prospective study revealed that urinary L-FABP (uL-FABP) was associated with a high probability of acute kidney injury after stem cell transplantation (SCT); however, the relevance of elevated uL-FABP to the prognosis of patients undergoing SCT remains to be determined. We aimed to investigate whether uL-FABP levels can be used to stratify patient prognosis after SCT. To achieve this aim, we conducted a new long-term follow-up study using data from patients enrolled in our preceding prospective cohort study. Patients were classified into high and low uL-FABP groups based on levels measured at baseline (ie, before initiating the conditioning regimen), using an uL-FABP cutoff of 8.4 µg/gCr, which was determined based on data from healthy adults. uL-FABP levels were also measured on days 0, 7, and 14 after SCT. Cox proportional hazard regression was used to examine the effects of each factor on survival outcomes, and Fine-Gray regression was used in the presence of competing risks. Multivariate analysis incorporating confounders was then performed for factors with P < .1 in univariate analysis. In total, 20 of 84 patients (23.8%), 57 of 84 patients (67.9%), 34 of 49 patients (69.4%), and 34 of 46 patients (73.9%) were classified into the high uL-FABP group at baseline and on days 0, 7, and 14, respectively. The 5-year overall survival (OS) rate was 23.9% in the high uL-FABP group and 68.9% in the low uL-FABP group. The multivariate analysis identified a high uL-FABP level at baseline as a significant prognostic factor for poor OS (hazard ratio [HR], 3.54; P = .002). The 5-year cumulative incidence rate for nonrelapse mortality (NRM) was 50.0% in the high uL-FABP group and 19.9% in the low uL-FABP group. In the multivariate analysis, high uL-FABP at baseline was a significant prognostic factor for NRM (HR, 3.37; P = .01). uL-FABP levels did not significantly stratify the cumulative incidence of relapse (HR, 2.13; P = .11). uL-FABP levels on days 0, 7, and 14 were not significant predictors of survival. High uL-FABP level before initiation of conditioning significantly influences OS and NRM following SCT, whereas a high uL-FABP level at any point after the conditioning regimen does not. Our results show that measuring uL-FABP level at baseline may be a simple way to predict survival in patients undergoing SCT.
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Proteínas de Ligação a Ácido Graxo , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Estudos Prospectivos , Seguimentos , Biomarcadores/urina , Prognóstico , Proteínas de Ligação a Ácido Graxo/urina , Transplante de Células-Tronco , FígadoRESUMO
Cytomegalovirus (CMV) infection is a major infectious complication following allogeneic hematopoietic cell transplantation (allo-HCT). Although letermovir (LMV) prophylaxis dramatically reduces the incidence of early clinically significant CMV (csCMV) infection, it remains unclear whether it has a beneficial effect on nonrelapse mortality (NRM) and overall survival (OS). Herein, we evaluated the impact of LMV prophylaxis on posttransplant outcomes using the registry database of the Japanese Society for Transplantation and Cellular Therapy. Adult patients who underwent allo-HCT between 2017 and 2019 were analyzed (n = 6004). LMV prophylaxis was administered to 1640 patients (LMV group) and it significantly reduced the incidence of csCMV infection compared with those not administered LMV prophylaxis (15.4% vs 54.1%; p < 0.01). However, it did not improve the 1-year NRM (hazard ratio [HR], 0.93; p = 0.40) and OS (HR, 0.96; p = 0.49). In the LMV group, 74 patients had breakthrough csCMV infection and showed inferior NRM (HR, 3.44; p < 0.01) and OS (HR, 1.93; p = 0.02) compared with those without infection. After completing LMV prophylaxis, 252 patients had late csCMV infection and showed inferior NRM (HR, 1.83; p < 0.01) and OS (HR, 1.58; p < 0.01). Our findings suggest that managing breakthrough and late csCMV infections is important for improving long-term outcomes.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Citomegalovirus , Antivirais/uso terapêutico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos RetrospectivosRESUMO
INTRODUCTION: With global adoption of computed tomography (CT) lung cancer screening, there is increasing interest to use artificial intelligence (AI) deep learning methods to improve the clinical management process. To enable AI research using an open-source, cloud-based, globally distributed, screening CT imaging data set and computational environment that are compliant with the most stringent international privacy regulations that also protect the intellectual properties of researchers, the International Association for the Study of Lung Cancer sponsored development of the Early Lung Imaging Confederation (ELIC) resource in 2018. The objective of this report is to describe the updated capabilities of ELIC and illustrate how this resource can be used for clinically relevant AI research. METHODS: In this second phase of the initiative, metadata and screening CT scans from two time points were collected from 100 screening participants in seven countries. An automated deep learning AI lung segmentation algorithm, automated quantitative emphysema metrics, and a quantitative lung nodule volume measurement algorithm were run on these scans. RESULTS: A total of 1394 CTs were collected from 697 participants. The LAV950 quantitative emphysema metric was found to be potentially useful in distinguishing lung cancer from benign cases using a combined slice thickness more than or equal to 2.5 mm. Lung nodule volume change measurements had better sensitivity and specificity for classifying malignant from benign lung nodules when applied to solid lung nodules from high-quality CT scans. CONCLUSIONS: These initial experiments revealed that ELIC can support deep learning AI and quantitative imaging analyses on diverse and globally distributed cloud-based data sets.
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Aprendizado Profundo , Enfisema , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patologia , Inteligência Artificial , Detecção Precoce de Câncer , Pulmão/patologia , Enfisema/patologiaRESUMO
PURPOSE: This study aimed to evaluate the performance of the commercially available artificial intelligence-based software CXR-AID for the automatic detection of pulmonary nodules on the chest radiographs of patients suspected of having lung cancer. MATERIALS AND METHODS: This retrospective study included 399 patients with clinically suspected lung cancer who underwent CT and chest radiography within 1 month between June 2020 and May 2022. The candidate areas on chest radiographs identified by CXR-AID were categorized into target (properly detected areas) and non-target (improperly detected areas) areas. The non-target areas were further divided into non-target normal areas (false positives for normal structures) and non-target abnormal areas. The visibility score, characteristics and location of the nodules, presence of overlapping structures, and background lung score and presence of pulmonary disease were manually evaluated and compared between the nodules detected or undetected by CXR-AID. The probability indices calculated by CXR-AID were compared between the target and non-target areas. RESULTS: Among the 450 nodules detected in 399 patients, 331 nodules detected in 313 patients were visible on chest radiographs during manual evaluation. CXR-AID detected 264 of these 331 nodules with a sensitivity of 0.80. The detection sensitivity increased significantly with the visibility score. No significant correlation was observed between the background lung score and sensitivity. The non-target area per image was 0.85, and the probability index of the non-target area was lower than that of the target area. The non-target normal area per image was 0.24. Larger and more solid nodules exhibited higher sensitivities, while nodules with overlapping structures demonstrated lower detection sensitivities. CONCLUSION: The nodule detection sensitivity of CXR-AID on chest radiographs was 0.80, and the non-target and non-target normal areas per image were 0.85 and 0.24, respectively. Larger, solid nodules without overlapping structures were detected more readily by CXR-AID.
Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Inteligência Artificial , Estudos Retrospectivos , Radiografia Torácica/métodos , Pulmão , Software , Radiografia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Sensibilidade e EspecificidadeRESUMO
Predicting the behaviour of solutions with surfactants of significantly different critical micelle concentration (CMC) values remains a challenge. The study of the molecular interactions within micelles and interfaces in surfactant combinations used in everyday products is essential to understand these complex systems. In this work, the equilibrium and dynamic surface tension in the presence of mixed non-ionic (tristyrylphenol ethoxylates) and anionic (sodium benzene sulfonate with alkyl chain lengths of C10-C13) surfactants, commonly encountered as delivery systems in agrochemicals, were studied and their CMC values were determined. For the surfactant mixtures, four molar ratios were examined: nEOT/nNaDDBS = 0.01, 0.1, 1, 4 and two different cases were analysed, the premixed and the add one by one surfactant. The surface tension for single surfactants stabilised quickly, while the mixtures needed a long time to reach equilibrium; up to 15 h for the premixed mixtures and 40 min when surfactants were added one by one. The CMC values for the nEOT/nNaDDBS = 0.01, 0.1 premixed surfactant mixtures were found to be in between the CMC values of the single surfactants, but those for the nEOT/nNaDDBS = 1 and 4 mixtures were lower than the CMCs of both single surfactants. Calculations based on the regular solution theory suggested that there are attractive forces in the mixed micelles and at the interface layers, while the supramolecular assemblies in the bulk (i.e., micelles) and at interfaces (surfactant films) are preferentially enriched in EOT.