Tag: nevin manimala

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):823-827. doi: 10.3760/cma.j.cn121430-20221229-01127.

ABSTRACT

OBJECTIVE: To investigate the application value of ROX index in evaluating the effect of high-flow nasal cannula oxygen therapy (HFNC) on patients diagnosed with respiratory failure, and to find a simpler and more effective method to observe the efficacy of HFNC.

METHODS: A retrospective cohort study was conducted. Patients who were admitted to department of critical care medicine of the Tianjin Third Central Hospital from April 2020 to August 2022, diagnosed with type I respiratory failure, and treated with HFNC after failure of conventional oxygen therapy were enrolled. Oxygenation index (PaO₂/FiO₂), fraction of inspired oxygen (FiO₂), gas flow rate at the initial time of admission, and pulse oxygen saturation (SpO₂), FiO₂ and respiratory rate (RR) at 2, 4, 6, 8, 10 and 12 hours of HFNC were collected, and ROX index was calculated. The patients with symptoms and PaO₂/FiO₂ improved after HFNC treatment and without higher respiratory support lately were defined as HFNC success, while other patients with symptoms worsening and needing follow-up non-invasive positive pressure ventilation (NIPPV) or invasive positive pressure ventilation (IPPV) were defined as HFNC failure. The tendency of changes in the ROX index at each time point was observed. Receiver operator characteristic curve (ROC curve) was plotted to obtain the optimum cut-off value of ROX index for predicting HFNC outcome and the optimal monitoring time point for HFNC.

RESULTS: A total of 142 patients were eventually enrolled, among whom 96 patients (67.61%) were in treated with HFNC successfully, while 46 patients (32.39%) were recorded as HFNC failure (39 patients and 7 patients received NIPPV or IPPV, respectively), with an overall intubation rate of 4.93% (7/142). Compared with the HFNC success group, the HFNC failure group had lower PaO₂/FiO₂ [mmHg (1 mmHg ≈ 0.133 kPa): 208.8±37.3 vs. 235.7±48.3, P < 0.01] and higher initial gas flow rate (L/min: 46.4±3.9 vs. 42.3±4.9, P < 0.01). However, there was no significant difference in gender, age, primary diagnosis, severity of disease, hemoglobin (Hb), C-reactive protein (CRP), and brain natriuretic peptide (BNP) between the two groups. In the HFNC failure group, there were 12 patients (26.09%) received progressive oxygen therapy within 12 hours of HFNC, of which 3 patients (6.52%) occurred within 6 hours, while the other 9 patients (19.57%) occurred after 6 hours. The initial ROX index was not statistically significant between the two groups. Both groups showed a continuous increasing ROX index with longer treatment duration of HFNC, and the ROX index at all of the time points of the HFNC failure group was significantly lower than that of the HFNC success group with statistically significant difference (2 hours: 9.39±2.85 vs. 10.91±3.51, 4 hours: 8.62±2.29 vs. 11.40±3.18, 6 hours: 7.62±1.65 vs. 11.85±3.45, 8 hours: 7.79±1.59 vs. 11.62±3.10, 10 hours: 7.97±1.62 vs. 12.44±2.75, 12 hours: 8.84±2.51 vs. 12.45±3.03, all P < 0.05). The ROC curve analysis showed that the areas under the ROC curve (AUC) of ROX index assessing the effect of HFNC at the time of treating 6, 8 and 10 hours were better than 2, 4 and 12 hours (0.890, 0.903, 0.930 vs. 0.585, 0.738 and 0.829), indicating that the ROX index could determine the efficacy at the early stage of HFNC (within 6 hours). When the optimum cut-off value of ROX index was 8.78, the sensitivity was 90.6%, and the specificity was 76.5%.

CONCLUSIONS: The ROX index at 6 hours of HFNC has a certain predictive value for the efficacy of HFNC with an optimum cut-off value of 8.78, which can provide clinical health care personnel a method for observing the efficacy of HFNC, and guide the correct selection of oxygen therapy modality at an early stage and timely adjustment of oxygen therapy strategy.

PMID:37593860 | DOI:10.3760/cma.j.cn121430-20221229-01127

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):818-822. doi: 10.3760/cma.j.cn121430-20221219-01105.

ABSTRACT

OBJECTIVE: To investigate the changes and clinical significance of multiple cytokine levels in exhaled breath condensate (EBC) in patients undergoing tracheotomy with severe inhalation injury.

METHODS: A prospective study was conducted. A total of 32 patients with severe burn combined with severe inhalation injury admitted to the department of burns and plastic surgery of Affiliated Suzhou Hospital of Nanjing Medical University from May 2021 to August 2022 were enrolled. Twenty healthy volunteers from the same period were served as controls. EBC of patients at 12 hours after burn and the samples of healthy controls were collected. The levels of 27 cytokines in EBC, including tumor necrosis factor-α (TNF-α) and interleukins (IL-1β, IL-6, IL-8, IL-10, and IL-17), were determined by liquid phase chip technology. Meanwhile, plasma of patients at 12 hours after burn and the plasma of volunteers were collected, and the levels of inflammatory cytokines were detected by liquid chip technology, and the differences between the levels in plasma and those in EBC were analyzed. Plasma and EBC of patients with aspiration injury were collected at 12 hours and 3, 7, 14 and 21 days after burn, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS: Finally, 32 patients were enrolled, and the total burned area was (40±16)% of total body surface area (TBSA). The time of admission was (4.2±2.3) hours after injury. (1) Twenty-seven cytokines in EBC: 18 kinds of cytokines including macrophage inflammatory protein-1β (MIP-1β), IL-6, IL-5, IL-2, IL-1β, IL-8, IL-10, IL-15, IL-9, interferon-γ (IFN-γ), IL-1 receptor antagonist (IL-1ra), TNF-α, chemotactic factor for eosinophil (Eotaxin), basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF) were significantly increased in patients with severe aspiration injury compared with health controls. Eotaxin was not detected in EBC of healthy controls. Five cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine ligand 5 (CCL5/RANTES), IL-13, IL-4 and MIP-1α, were not detected in EBC of severe inhalation injury patients and healthy controls. Vascular endothelial growth factor (VEGF) and IL-12 p70 in EBC of severe aspiration injury patients were slightly decreased as compared with healthy controls, while IL-7 and IL-17 were slightly increased, but the differences were not statistically significant. (2) Six inflammatory cytokines in plasma: the levels of IL-6 and IL-8 in the severe aspiration injury group were significantly increased as compared with healthy controls [IL-6 (ng/L): 18.51 (10.87, 26.21) vs. 0.22 (0.10, 0.36), IL-8 (ng/L): 10.75 (8.58, 18.79) vs. 1.06 (0.81, 2.14), both P < 0.01]. The plasma levels of TNF-α, IL-1β and IL-10 were slightly increased in patients with severe aspiration injury as compared with healthy controls, and IL-17 was slightly decreased, but the difference was not statistically significant. In the EBC collected during the same period, five inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8 and IL-10, in patients with severe inhalation injury were significantly increased as compared with healthy controls [TNF-α (ng/L): 16.42 (12.57, 19.21) vs. 7.34 (6.11, 8.69), IL-1β (ng/L): 15.57 (10.53, 20.25) vs. 0.99 (0.67, 1.41), IL-6 (ng/L): 13.36 (9.76, 16.54) vs. 0.70 (0.42, 0.85), IL-8 (ng/L): 1 059.29 (906.91, 1 462.37) vs. 10.36 (8.40, 12.37), IL-10 (ng/L): 2.69 (1.54, 3.33) vs. 1.54 (1.18, 2.06), all P < 0.05]. (3) Dynamic changes of TNF-α in plasma and EBC: the level of TNF-α in EBC of patients with severe aspiration injury was lower than that in plasma. Plasma TNF-α level was increased gradually with the extension of time after injury, and was significantly higher than that of healthy controls on day 3 [ng/L: 30.38 (24.32, 39.19) vs. 22.94 (17.15, 30.74), P < 0.05], and reached the peak on day 14, then fell back. The level of TNF-α in EBC at 12 hours after injury was significantly higher than that in healthy controls [ng/L: 15.34 (11.75, 18.14) vs. 6.99 (6.53, 7.84), P < 0.01], and reached the peak on 3 days after injury, and then gradually decreased.

CONCLUSIONS: There are changes in the expression of multiple cytokines in EBC of patients with severe inhalation injury, and the changes of many inflammatory cytokines including TNF-α are more sensitive than those in plasma, which can be used to monitor and evaluate the condition of patients with inhalation injury.

PMID:37593859 | DOI:10.3760/cma.j.cn121430-20221219-01105

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):793-799. doi: 10.3760/cma.j.cn121430-20230510-00158.

ABSTRACT

OBJECTIVE: To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups.

METHODS: A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People’s Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH.

RESULTS: Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio (OR) = 0.997, 95% confidence interval (95%CI) was 0.996-0.998], D-dimer (OR = 0.960, 95%CI was 0.944-0.977), LDH (OR = 0.998, 95%CI was 0.997-0.999) and TG (OR = 0.706, 95%CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer (OR = 1.001, 95%CI was 1.001-1.002), LDH (OR = 1.004, 95%CI was 1.002-1.005) and D-dimer (OR = 1.036, 95%CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients (OR = 7.692, 95%CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95%CI was 0.866-0.973, P = 0.000].

CONCLUSIONS: Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.

PMID:37593855 | DOI:10.3760/cma.j.cn121430-20230510-00158

Plant Biotechnol J. 2023 Aug 18. doi: 10.1111/pbi.14126. Online ahead of print.

ABSTRACT

We present an easy-to-reproduce manual miniaturized full-length RNA sequencing (RNAseq) library preparation workflow that does not require the upfront investment in expensive lab equipment or long setup times. With minimal adjustments to an established commercial protocol, we were able to manually miniaturize the RNAseq library preparation by a factor of up to 1:8. This led to cost savings for miniaturized library preparation of up to 86.1% compared to the gold standard. The resulting data were the basis of a rigorous quality control analysis that inspected: sequencing quality metrics, gene body coverage, raw read duplications, alignment statistics, read pair duplications, detected transcripts and sequence variants. We also included a deep dive data analysis identifying rRNA contamination and suggested ways to circumvent these. In the end, we could not find any indication of biases or inaccuracies caused by the RNAseq library miniaturization. The variance in detected transcripts was minimal and not influenced by the miniaturization level. Our results suggest that the workflow is highly reproducible and the sequence data suitable for downstream analyses such as differential gene expression analysis or variant calling.

PMID:37593840 | DOI:10.1111/pbi.14126

Sci Diabetes Self Manag Care. 2023 Aug 18:26350106231192353. doi: 10.1177/26350106231192353. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to compare the benefits of a diabetes self-management program led by registered nurses (RNs) versus community health workers (promotores) for Spanish-speaking Mexican Americans with type 2 diabetes (T2DM).

METHODS: Three hundred thirty Spanish-speaking Mexican American adults with T2DM were randomly assigned to “Tomando Control de Su Diabetes” delivered for six 2.5-hour sessions either by promotores or RNs. The primary outcome measure was the Summary of Diabetes Self-Care Activities (SDSCA). Evaluations were made at baseline, 6 weeks, and at 3, 6, and 12 months. Mixed-effects regression models were fit to test if participants had differential changes in the SDSCA total score by group over time, controlling for demographic and clinical factors.

RESULTS: SDSCA scores were significantly higher at all time points compared to baseline and not statistically different between the 2 groups. Only years of education correlated with improvement in diabetes self-management behaviors. No moderating variables predicted improvement between groups.

CONCLUSIONS: Spanish-speaking Mexican American adults with T2DM who participated in a diabetes educational program with promotores or RNs demonstrated similar improvements. Promotores may increase the accessibility of effective diabetes self-management training for this difficult-to-reach population.

PMID:37593833 | DOI:10.1177/26350106231192353

J Orthop Res. 2023 Aug 18. doi: 10.1002/jor.25680. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the muscle activation of the vastus medialis, vastus lateralis, and gluteus medius during different strength and stability exercises with a water tank compared to a sandbag. A cross-sectional study was conducted in the Functional Anatomy Laboratory, and the sample consisted of 28 athletes. The main outcome measures were surface electromyography (dependent variable), water tank and sandbag, and exercise type (independent variables): Isometric Single Leg Stance (ISLS), One Leg Deadlift (OLDL), Front Rack Forward Lunge (FRFL), and Lateral Lunge (LL). Repeated measures ANOVA revealed a significant Group*Time interaction in gluteus medius Root Mean Square (RMS) (F=14.198, p<0.001, ŋ2=0.35), vastus lateralis RMS (F=24.374, p<0.001, ŋ2=0.47), and vastus medialis RMS (F=27.261, p<0.001, ŋ2=0.50). In the between-group analysis, statistically significant differences were observed in gluteus medius RMS in the ISLS: 28.5±15.8 water tank and 20.8±12.6 sandbag (p<0.001, ŋ2=0.08) and OLDL: 29.7±13.3 water tank and 26.5±13.1 sandbag (p<0.001, ŋ2=0.01). In vastus lateralis in ISLS: 30.4±37.6 water tank and 19.0±26.7 sandbag (p<0.001, ŋ2=0.03). In vastus medialis in ISLS: 14.2±13.0 water tank and 7.0±5.6 sandbag (p<0.001, ŋ2=0.12), OLDL: 21.5±16.9 water tank and 15.5±10.7 sandbag (p=0.002, ŋ2=0.04), and LL: 51.8±29.6 water tank and 54.3±29.3 sandbag (p=0.017, ŋ2=0.00). These results confirm significantly greater activation of the gluteus medius and vastus medialis in the ISLS and OLDL exercises, and of the vastus lateralis in the water tank ISLS exercise. However, the vastus medialis shows greater activation in the LL exercise. This article is protected by copyright. All rights reserved.

PMID:37593805 | DOI:10.1002/jor.25680

Stat Med. 2023 Sep 20;42(21):3745-3763. doi: 10.1002/sim.9829. Epub 2023 Jun 13.

ABSTRACT

Hierarchical data arise when observations are clustered into groups. Multilevel models are practically useful in these settings, but these models are elusive in the context of hierarchical data with mixed multivariate outcomes. In this article, we consider binary and survival outcomes and assume the hierarchical structure is induced by clustering of both outcomes within patients and clustering of patients within hospitals which frequently occur in multicenter studies. We introduce a multilevel joint frailty model that analyzes the outcomes simultaneously to jointly estimate their regression parameters and explicitly model within-patient correlation between the outcomes and within-hospital correlation separately for each outcome. Estimation is facilitated by a computationally efficient residual maximum likelihood method that further predicts cluster-specific frailties for both outcomes and circumvents the formidable challenges induced by multidimensional integration that complicates the underlying likelihood. The performance of the model and estimation procedure is investigated via extensive simulation studies. The practical utility of the model is illustrated through simultaneous modeling of disease-free survival and binary endpoint of platelet recovery in a multicenter allogeneic bone marrow transplantation dataset that motivates this study.

PMID:37593802 | DOI:10.1002/sim.9829

Birth. 2023 Aug 18. doi: 10.1111/birt.12752. Online ahead of print.

ABSTRACT

BACKGROUND: Over one-third of nulliparae planning births either at home or in freestanding midwife-led birthing centers (community births) in high-income countries are transferred during labor. Perinatal data are reported each year in Germany for women planning community birth. So far, data sets have not been linked to describe time-related factors associated with nulliparous transfer to hospital.

OBJECTIVES: To describe the prevalence of referral for nulliparae and assess maternal and labor characteristics associated with intrapartum transfer.

METHODS: Perinatal data from 2010 to 2015 were linked (n = 26,115). Women were reviewed with respect to international eligibility criteria for community birth; 1997 women were excluded (7.6%). Descriptive statistics were reported; unadjusted and adjusted odds ratios with 95% confidence intervals (CI) tested the predictive effect of demographic and labor factors on rates of intrapartum transfer.

RESULTS: One in three nulliparous women (30.6%) were transferred to hospital. Compared with community births, transferred women were significantly more likely to experience longer time intervals during labor: from rupture of membranes (ROM) until birth lasting 5 to 18 h (OR 6.05, CI 5.53-6.61) and 19 to 24 h (OR 10.83, CI 9.45-12.41) compared to one to 4 h; and from onset of labor until birth 11 to 24 h (OR 6.72, CI 6.24-7.23) and 25 to 29 h (OR 26.62, CI 22.77-31.11) compared to one to 10 h. When entering all factors into the model, we found the strongest predictors of transfer to be fetal distress, longer time intervals between ROM until birth and onset of labor until birth.

CONCLUSIONS: Nulliparous transfer rates were similar to rates in other high-income countries; 94% of referrals were non-urgent. Time was found to be an independent risk factor for the transfer of nulliparae planning community birth.

PMID:37593788 | DOI:10.1111/birt.12752

Front Immunol. 2023 Aug 1;14:1235370. doi: 10.3389/fimmu.2023.1235370. eCollection 2023.

ABSTRACT

BACKGROUND: Macrophage colony-stimulating factor 2 (MCSF-2) is an important cytokine that controls how cells of the monocyte/macrophage lineage proliferate, differentiate, and survive in vertebrates. Two isoforms of MCSF have been identified in fish, each exhibiting distinct gene organization and expression patterns. In this study, we investigated a goldfish MCSF-2 gene in terms of its immunomodulatory and functional properties.

METHODS: In this study, goldfish were acclimated for 3 weeks and sedated with TMS prior to handling. Two groups of fish were used for infection experiments, and tissues from healthy goldfish were collected for RNA isolation. cDNA synthesis was performed, and primers were designed based on transcriptome database sequences. Analysis of gfMCSF-2 sequences, including nucleotide and amino acid analysis, molecular mass prediction, and signal peptide prediction, was conducted. Real-time quantitative PCR (qPCR) was used to analyze gene expression levels, while goldfish head kidney leukocytes (HKLs) were isolated using standard protocols. The expression of gfMCSF-2 in activated HKLs was investigated, and recombinant goldfish MCSF-2 was expressed and purified. Western blot analysis, cell proliferation assays, and flow cytometric analysis of HKLs were performed. Gene expression analysis of transcription factors and pro-inflammatory cytokines in goldfish head kidney leukocytes exposed to rgMCSF-2 was conducted. Statistical analysis using one-way ANOVA and Dunnett’s post hoc test was applied.

RESULTS: We performed a comparative analysis of MCSF-1 and MCSF-2 at the protein and nucleotide levels using the Needleman-Wunsch algorithm. The results revealed significant differences between the two sequences, supporting the notion that they represent distinct genes rather than isoforms of the same gene. Sequence alignment demonstrated high sequence identity with MCSF-2 homologs from fish species, particularly C. carpio, which was supported by phylogenetic analysis. Expression analysis in various goldfish tissues demonstrated differential expression levels, with the spleen exhibiting the highest expression. In goldfish head kidney leukocytes, gfMCSF-2 expression was modulated by chemical stimuli and bacterial infection, with upregulation observed in response to lipopolysaccharide (LPS) and live Aeromonas hydrophila. Recombinant gfMCSF-2 (rgMCSF-2) was successfully expressed and purified, showing the ability to stimulate cell proliferation in HKLs. Flow cytometric analysis revealed that rgMCSF-2 induced differentiation of sorted leukocytes at a specific concentration. Moreover, rgMCSF-2 treatment upregulated TNFα and IL-1β mRNA levels and influenced the expression of transcription factors, such as MafB, GATA2, and cMyb, in a time-dependent manner.

CONCLUSION: Collectively, by elucidating the effects of rgMCSF-2 on cell proliferation, differentiation, and the modulation of pro-inflammatory cytokines and transcription factors, our findings provided a comprehensive understanding of the potential mechanisms underlying gfMCSF-2-mediated immune regulation. These results contribute to the fundamental knowledge of MCSF-2 in teleosts and establish a foundation for further investigations on the role of gfMCSF-2 in fish immune responses.

PMID:37593738 | PMC:PMC10431942 | DOI:10.3389/fimmu.2023.1235370

Front Immunol. 2023 Aug 1;14:1208814. doi: 10.3389/fimmu.2023.1208814. eCollection 2023.

ABSTRACT

Alloreactive donor-derived T-cells play a pivotal role in alloimmune responses after allogeneic hematopoietic stem cell transplantation (alloSCT); both in the relapse-preventing Graft-versus-Leukemia (GvL) effect and the potentially lethal complication Graft-versus-Host-Disease (GvHD). The balance between GvL and GvHD can be shifted by removing T-cells via T-cell depletion (TCD) to reduce the risk of GvHD, and by introducing additional donor T-cells (donor lymphocyte infusions [DLI]) to boost the GvL effect. However, the association between T-cell kinetics and the occurrence of allo-immunological events has not been clearly demonstrated yet. Therefore, we investigated the complex associations between the T-cell kinetics and alloimmune responses in a cohort of 166 acute leukemia patients receiving alemtuzumab-based TCD alloSCT. Of these patients, 62 with an anticipated high risk of relapse were scheduled to receive a prophylactic DLI at 3 months after transplant. In this setting, we applied joint modelling which allowed us to better capture the complex interplay between DLI, T-cell kinetics, GvHD and relapse than traditional statistical methods. We demonstrate that DLI can induce detectable T-cell expansion, leading to an increase in total, CD4+ and CD8+ T-cell counts starting at 3 months after alloSCT. CD4+ T-cells showed the strongest association with the development of alloimmune responses: higher CD4 counts increased the risk of GvHD (hazard ratio 2.44, 95% confidence interval 1.45-4.12) and decreased the risk of relapse (hazard ratio 0.65, 95% confidence interval 0.45-0.92). Similar models showed that natural killer cells recovered rapidly after alloSCT and were associated with a lower risk of relapse (HR 0.62, 95%-CI 0.41-0.93). The results of this study advocate the use of joint models to further study immune cell kinetics in different settings.

PMID:37593737 | PMC:PMC10427852 | DOI:10.3389/fimmu.2023.1208814