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AIMS: This review examined the impact of virtual reality (VR) training on nursing students' clinical skill performance and identified essential features of VR training. BACKGROUND: VR provides immersive content, simulating real-life scenarios and preventing errors in clinical settings. DESIGN: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. DATA SOURCES: Studies were obtained from Ovid-EMBASE, MEDLINE, CINAHL and PubMed. REVIEW METHODS: Studies related to VR training published from 1 January 2000 to 8 May 2024 were included. Comprehensive Meta-Analysis 4.0 software was used for meta-analysis and random effects meta-regression. The overall effect was assessed with Hedges' g and Z-statistics (p < 0.05). Heterogeneity was measured using I-squared (I2) statistics. RESULTS: Among the 31 476 studies, 11 randomized controlled trial studies were included. Meta-analysis demonstrated a significant improvement in clinical skill performance, with a medium to large effect (g = 0.61) in the VR group (Z = 3.80, p < 0.001). Subgroup analyses highlighted higher nursing skills in the VR training topic. Meta-regression revealed that the VR training topic (ß = 1.23, p < 0.001) and method of VR training (ß = -0.53, p = 0.05) were significant covariates influencing clinical skill performance. CONCLUSION: VR training improves nursing students' clinical skill performance, addressing shortcomings in the clinical practicum.
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Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.
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BACKGROUND: Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. OBJECTIVES: To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. METHODS: We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. RESULTS: A total of 3296 BSI episodes with 454â419â days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), Pâ=â0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, Pâ<â0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, Pâ=â0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all Pâ<â0.05). However, Pseudomonas aeruginosa BSI increased. CONCLUSIONS: Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.
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Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Análisis de Series de Tiempo Interrumpido , Humanos , Estudios Longitudinales , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Farmacorresistencia Bacteriana , Leucemia/tratamiento farmacológico , Leucemia/complicaciones , Utilización de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/normasRESUMEN
PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.
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Small animal caregivers' perceptions and previous life experiences play a pivotal role in patient care, making effective communication fundamental within the veterinary business. Despite the large and growing scale of the pet industry, data on small animal client-centered information about veterinary services in Mainland China (MC) and the Hong Kong Special Administrative Region (HKSAR) China are lacking. The objective of this study was to investigate the perceptions and opinions of small animal caregivers about surgery, pain management, and anesthesia in dogs and cats in these geographical regions through a validated online survey using content validity index. A total of 2080 valid answers were collected by convenience sampling over 45 days. Descriptive statistics were used to summarize data; the chi-square test and generalized linear models were used to test the associations between demographics and responses. Overall, caregivers appeared favorable toward the use of analgesia in their pets, with concerns over the potential adverse effects produced by analgesic drugs. Joint pain and ear infections were generally rated as conditions that would be less prone to require analgesia. Significant associations were observed for demographic factors such as gender, age, and geographical area, whether participants were healthcare providers, and whether their pets had undergone surgery before. Although many respondents expressed uncertainty in recognizing pain in their pets and administering analgesics, they also expressed a desire to learn and to be informed. This study highlights areas and factors that may determine the perceptions and opinions of small animal caregivers that form a unique human-animal bond in China. Client communication should be addressed on a case-by-case basis and adapted to the geographical area, as the individual background and demographics may have an ultimate impact on treatment goals and patient care.
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DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, the precise roles of these variants in the pathogenesis of MDS have yet to be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes to R-loop-induced DNA damage responses (DDR) in cooperation with the m6A-METTL complex (MAC) and YTHDC1 using DDX41 knockout (KO) and DDX41 knock-in (KI, R525H, Y259C) cell lines as well as primary samples from MDS patients. Compared to wild type (WT), DDX41 KO and KI led to increased levels of m6A RNA methylated R-loop. Interestingly, we found that DDX41 regulates m6A/R-loop levels by interacting with MAC components. Further, DDX41 promoted the recruitment of YTHDC1 to R-loops by promoting the binding between METTL3 and YTHDC1, which was dysregulated in DDX41-deficient cells, contributing to genomic instability. Collectively, we demonstrated that DDX41 plays a key role in the physiological control of R-loops in cooperation with MAC and YTHDC1. These findings provide novel insights into how defects in DDX41 influence MDS pathogenesis and suggest potential therapeutic targets for the treatment of MDS.
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ARN Helicasas DEAD-box , Metiltransferasas , Mutación , Síndromes Mielodisplásicos , Factores de Empalme de ARN , Humanos , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/metabolismo , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , Estructuras R-Loop , Daño del ADN , Unión Proteica , Proteínas del Tejido NerviosoRESUMEN
In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.
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Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Humanos , Acondicionamiento Pretrasplante/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adulto , Neoplasia Residual , Trasplante Homólogo/métodos , Anciano , Adolescente , Adulto Joven , Agonistas Mieloablativos/uso terapéutico , AloinjertosRESUMEN
Snakebite envenoming is a major global public health concern for which improved therapies are urgently needed. The antigenic diversity present in snake venom toxins from various species presents a considerable challenge to the development of a universal antivenom. Here, we used a synthetic human antibody library to find and develop an antibody that neutralizes long-chain three-finger α-neurotoxins produced by numerous medically relevant snakes. Our antibody bound diverse toxin variants with high affinity, blocked toxin binding to the nicotinic acetylcholine receptor in vitro, and protected mice from lethal venom challenge. Structural analysis of the antibody-toxin complex revealed a binding mode that mimics the receptor-toxin interaction. The overall workflow presented is generalizable for the development of antibodies that target conserved epitopes among antigenically diverse targets, and it offers a promising framework for the creation of a monoclonal antibody-based universal antivenom to treat snakebite envenoming.
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Antivenenos , Mordeduras de Serpientes , Humanos , Animales , Ratones , Antivenenos/química , Mordeduras de Serpientes/tratamiento farmacológico , Neurotoxinas/toxicidad , Anticuerpos ampliamente neutralizantes , Venenos de SerpienteRESUMEN
BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil. METHODS: This retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment. RESULTS: During the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil. CONCLUSION: Intravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.
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Epoprostenol/análogos & derivados , Hipertensión Pulmonar , Lactante , Recién Nacido , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Recien Nacido Prematuro , Óxido Nítrico , Estudios Retrospectivos , Antihipertensivos/uso terapéuticoRESUMEN
BACKGROUND: Several cases of pediatric acute hepatitis of unknown etiology related to adenoviral infections have been reported in Europe since January 2022. The aim of this study was to compare the incidence, severity, possible etiology, and prognosis of the disease with those in the past in Korea. METHODS: The surveillance group collected data between May and November 2022 using a surveillance system. Acute hepatitis of unknown etiology was defined in patients aged < 16 years with a serum transaminase level > 500 IU/L, not due to hepatitis A-E or other underlying causes. For comparison, data from 18 university hospitals were retrospectively collected as a control group between January 2021 and April 2022. RESULTS: We enrolled 270 patients (mean age, 5 years). The most common symptom was fever. However, the incidence was similar between 2021 and 2022. Liver function test results, number of patients with acute liver failure (ALF), liver transplantation (LT), death, and adenovirus detection rates did not differ between the two groups. None of the adenovirus-positive patients in either group experienced ALF, LT, or death. In the surveillance group, adenovirus-associated virus-2 was detected in four patients, one of whom underwent LT. Patients with an unknown etiology showed significantly higher bilirubin levels, a lower platelet count, and a higher LT rate than patients with a possible etiology. CONCLUSION: The incidence of pediatric acute hepatitis of unknown etiology and adenovirus detection rate have not increased in Korea.
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Hepatitis , Fallo Hepático Agudo , Trasplante de Hígado , Humanos , Niño , Preescolar , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Pronóstico , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/epidemiología , Fallo Hepático Agudo/etiología , Enfermedad Aguda , Adenoviridae , República de Corea/epidemiologíaRESUMEN
Introduction: Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking. Methods: Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined. Results: All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival. Discussion: This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.
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During cervical carcinogenesis, T-helper (Th)-17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse; however, the underlying Th17-driven mechanisms are not fully understood. Here, using microarrays, we found that Th17 cells induced an epithelial-to-mesenchymal transition (EMT) phenotype of cervical cancer cells and promoted migration and invasion of 2D cultures and 3D spheroids via induction of microRNA miR-142-5p. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR-142-5p and provided evidence that Th17-miR-142-5p-dependent reduced expression of SDHC and SDHD mediated enhanced migration and invasion of cancer cells using small interfering RNAs (siRNAs) for SDHC and SDHD, and miR-142-5p inhibitors. Consistently, patients exhibited high levels of succinate in their serum associated with lymph node metastases and diminished expression of SDHD in patient biopsies correlated with increased numbers of Th17 cells. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells > 43.90% in situ was associated with reduced recurrence-free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.
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To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia/terapia , Linfoma no Hodgkin/terapia , Linfoma de Células B Grandes Difuso/terapia , Estudios RetrospectivosRESUMEN
The prevention and management of cytomegalovirus (CMV) reactivation is important to improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data regarding the incidence and characteristics of CMV infections until 1 year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14 weeks, 24 weeks, and 1 year post-HCT, respectively. Through multivariate analysis, the risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036-6.510]; p < 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued receiving letermovir (p = 0.002). There were 18 (15.9%) refractory CMV infection cases in this study population. In summary, letermovir prophylaxis is effective at preventing CS-CMVi until day 100, which increased after the cessation of letermovir. GVHD is still a significant risk factor in the era of letermovir prophylaxis. Further research is needed to establish individualized management strategies, especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.
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Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/prevención & controlRESUMEN
BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.
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Bronquiolitis Obliterante , Trasplante de Células Madre Hematopoyéticas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Bromuro de Tiotropio/uso terapéutico , Budesonida/uso terapéutico , Estudios Retrospectivos , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/etiología , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , BroncodilatadoresRESUMEN
BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.
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Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Trasplante Autólogo , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Antígenos CD34 , Moléculas de Adhesión Celular , RecurrenciaRESUMEN
In recent years, with the approval of preventative vaccines for pandemics, lipid nanoparticles have become a prominent RNA delivery vehicle. The lack of long-lasting effects of non-viral vectors is an advantage for infectious disease vaccines. With the introduction of microfluidic processes that facilitate the encapsulation of nucleic acid cargo, lipid nanoparticles are being studied as delivery vehicles for various RNA-based biopharmaceuticals. In particular, using microfluidic chip-based fabrication processes, nucleic acids such as RNA and proteins can be effectively incorporated into lipid nanoparticles and utilized as delivery vehicles for various biopharmaceuticals. Due to the successful development of mRNA therapies, lipid nanoparticles have emerged as a promising approach for the delivery of biopharmaceuticals. Biopharmaceuticals of various types (DNA, mRNA, short RNA, proteins) possess expression mechanisms that are suitable for manufacturing personalized cancer vaccines, while also requiring formulation with lipid nanoparticles. In this review, we describe the basic design of lipid nanoparticles, the types of biopharmaceuticals used as carriers, and the microfluidic processes involved. We then present research cases focusing on lipid-nanoparticle-based immune modulation and discuss the current status of commercially available lipid nanoparticles, as well as future prospects for the development of lipid nanoparticles for immune regulation purposes.
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To design a new system of novel TEMPO-oxidized cellulose nanofibrils (TOCNs)/graphene oxide (GO) composite, 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation was utilized. For the better dispersion of GO into the matrix of nanofibrillated cellulose (NFC), a unique process combining high-intensity homogenization and ultrasonication was adopted with varying degrees of oxidation and GO percent loadings (0.4 to 2.0 wt%). Despite the presence of carboxylate groups and GO, the X-ray diffraction test showed that the crystallinity of the bio-nanocomposite was not altered. In contrast, scanning electron microscopy showed a significant morphological difference in their layers. The thermal stability of the TOCN/GO composite shifted to a lower temperature upon oxidation, and dynamic mechanical analysis signified strong intermolecular interactions with the improvement in Young's storage modulus and tensile strength. Fourier transform infrared spectroscopy was employed to observe the hydrogen bonds between GO and the cellulosic polymer matrix. The oxygen permeability of the TOCN/GO composite decreased, while the water vapor permeability was not significantly affected by the reinforcement with GO. Still, oxidation enhanced the barrier properties. Ultimately, the newly fabricated TOCN/GO composite through high-intensity homogenization and ultrasonification can be utilized in a wide range of life science applications, such as the biomaterial, food, packaging, and medical industries.
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Background: Self-care is essential for stroke survivors to recover from neurological disorders caused by stroke and to prevent recurrences. Self-care behaviors are activities that individuals undertake to prevent recurrence and complications, and have a positive effect on the quality of life of patients. Telehealth is an emerging technology through which self-care intervention can be provided from a distance. Review-based research is needed to determine the value and development of telehealth-based self-care interventions for stroke survivors. Objective: Based on the middle range theory of self-care of chronic illness, to provide an effective guide when developing telehealth self-care interventions for stroke survivors by comprehensively understanding telehealth interventions to support self-care of stroke survivors. Methods: An integrative review, this study was performed in accordance with Whittemore and Knafl's stages of an integrative review (problem identification, literature search, data evaluation, data analysis, and presentation of the results). The key search terms included combinations of concepts related to stroke survivors and self-care, and telehealth. The research year of searched publications was not limited, and five electronic databases (PubMed, Ovid-MEDLINE, Ovid-EMBASE, CINAHL and Cochrane Library) were searched. Results: Four attributes were identified that represented telehealth's functions that appeared to be associated with a self-care intervention for stroke survivors. These included introducing the concept of interaction, monitoring, education, and store and forward. These self-care interventions were found to influence the behaviors of stroke survivors' self-care maintenance (physical activity and treatment adherence), self-care monitoring (blood pressure, healthy behaviors, health diet, psychological well-being, glucose control, and depression), and self-care management (sense of control, healthcare resource utilization, social integration, and support). Conclusions: The results of this study can provide a guide for developing effective telehealth self-care intervention by identifying the attributes of telehealth self-care intervention for stroke survivors.
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Recently, miraculous therapy approaches involving adeno-associated virus (AAV) for incurable diseases such as spinal muscular atrophy and inherited retinal dysfunction have been introduced. Nonreplicative, nonpathogenic, low rates of chromosome insertional properties and the existence of neutralizing antibodies are main safety reasons why the FDA approved its use in gene delivery. To date, AAV production always results in a mixture of nontherapeutic (empty) and therapeutic (DNA-loaded) full capsids (10-98%). Such existence of empty viral particles inevitably increases viral doses to human. Thus, the rapid monitoring of empty capsids and reducing the empty-to-full ratio are critical in AAV science. However, transmission electron microscopy (TEM) is the primary tool for distinguishing between empty and full capsids, which creates a research bottleneck because of instrument accessibility and technical difficulty. Herein, we demonstrate that atomic force microscopy (AFM) can be an alternative tool to TEM. The simple, noncontact-mode imaging of AAV particles allows the distinct height difference between full capsids (â¼22 nm) and empty capsids (â¼16 nm). The sphere-to-ellipsoidal morphological distortion observed for empty AAV particles clearly distinguishes them from full AAV particles. Our study indicates that AFM imaging can be an extremely useful, quality-control tool in AAV particle monitoring, which is beneficial for the future development of AAV-based gene therapy.