High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern.

To date, nearly one-quarter of colorectal cancer (CRC) patients develop liver metastases (CRCLM), and its aggressiveness can be correlated to defined histopathological growth patterns (HGP). From the three main HGPs within CRCLM, the replacement HGP emerges as particularly aggressive, characterized by heightened tumor cell motility and vessel co-option. Here, we investigated the correlation between the expression of calcium- and integrin-binding protein 1 (CIB1), a ubiquitously expressed gene involved in various cellular processes including migration and adhesion, and disease-free (DFS) and overall survival (OS) in primary CRC patients. Additionally, we explored the correlation between CIB1 expression and different HGPs of CRCLM. Proteomic analysis was used to evaluate CIB1 expression in a cohort of 697 primary CRC patients. Additionally, single-cell and spatial RNA-sequencing datasets, along with publicly available bulk sequencing data were used to evaluate CIB1 expression in CRCLM. In silico data were further validated by formalin-fixed paraffin-embedded immunohistochemical stainings. We observed that high CIB1 expression is independently associated with worse DFS and OS, regardless of Union Internationale Contre le Cancer stage, gender, or age. Furthermore, the aggressive replacement CRCLM HGP is significantly associated with high CIB1 expression. Our findings show a correlation between CIB1 levels and the clinical aggressiveness of CRC. Moreover, CIB1 may be a novel marker to stratify HGP CRCLM.

Tumor Vessel Normalization via PFKFB3 Inhibition Alleviates Hypoxia and Increases Tumor Necrosis in Rectal Cancer upon Radiotherapy.

Treatment of patients with locally advanced rectal cancer (RC) is based on neoadjuvant chemoradiotherapy followed by surgery. In order to reduce the development of therapy resistance, it is necessary to further improve previous treatment approaches. Recent in vivo experimental studies suggested that the reduction of tumor hypoxia by tumor vessel normalization (TVN), through the inhibition of the glycolytic activator PFKFB3, could significantly improve tumor response to therapy. We have evaluated in vitro and in vivo the effects of the PFKFB3 inhibitor 2E-3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) on cell survival, clonogenicity, migration, invasion, and metabolism using colorectal cancer cells, patient-derived tumor organoid (PDO), and xenograft (PDX). 3PO treatment of colorectal cancer cells increased radiation-induced cell death and reduced cancer cell invasion. Moreover, gene set enrichment analysis shows that 3PO is able to alter the metabolic status of PDOs toward oxidative phosphorylation. Additionally, in vivo neoadjuvant treatment with 3PO induced TVN, alleviated tumor hypoxia, and increased tumor necrosis. Our results support PFKFB3 inhibition as a possible future neoadjuvant addition for patients with RC. SIGNIFICANCE: Novel therapies to better treat colorectal cancer are necessary to improve patient outcomes. Therefore, in this study, we evaluated the combination of a metabolic inhibitor (3PO) and standard radiotherapy in different experimental settings. We have observed that the addition of 3PO increased radiation effects, ultimately improving tumor cell response to therapy.

Heterostructures Assembled from Bi2O2CO3 and MXene for Boosted Potassium-Ion Storage by Arousing the Built-in Electric Field.

Bismuth-based materials have been recognized as the appealing anodes for potassium-ion batteries (PIBs) due to their high theoretical capacity. However, the kinetics sluggishness and capacity decline induced by the structure distortion predominately retard their further development. Here, a heterostructure of polyaniline intercalated Bi2O2CO3/MXene (BOC-PA/MXene) hybrids is reported via simple self-assembly strategy. The ingenious design of heterointerface-rich architecture motivates significantly the interior self-built-in electric field (IEF) and high-density electron flow, thus accelerating the charge transfer and boosting ion diffusion. As a result, the hybrids realize a high reversible specific capacity, satisfying rate capability as well as long-term cycling stability. The in/ex situ characterizations further elucidate the stepwise intercalation-conversion-alloying reaction mechanism of BOC-PA/MXene. More encouragingly, the full cell investigation further highlights its competitive merits for practical application in further PIBs. The present work not only opens the way to the design of other electrodes with an appropriate working mechanism but also offers inspiration for built-in electric-field engineering toward high-performance energy storage devices.

Polypyrrole pre-intercalation engineering-induced NH4+ removal in tunnel ammonium vanadate toward high-performance zinc ion batteries.

Ammonium vanadate with stable bi-layered structure and superior mass-specific capacity have emerged as competitive cathode materials for aqueous rechargeable zinc-ion batteries (AZIBs). Nevertheless, fragile NH…O bonds and too strong electrostatic interaction by virtue of excessive NH4+ will lead to sluggish Zn2+ ion mobility, further largely affects the electro-chemical performance of ammonium vanadate in AZIBs. The present work incorporates polypyrrole (PPy) to partially replace NH4+ in NH4V4O10 (NVO), resulting in the significantly enlarged interlayers (from 10.1 to 11.9 Å), remarkable electronic conductivity, increased oxygen vacancies and reinforced layered structure. The partial removal of NH4+ will alleviate the irreversible deammoniation to protect the laminate structures from collapse during ion insertion/extraction. The expanded interlayer spacing and the increased oxygen vacancies by the virtue of the introduction of polypyrrole improve the ionic diffusion, enabling exceptional rate performance of NH4V4O10. As expected, the resulting polypyrrole intercalated ammonium vanadate (NVOY) presents a superior discharge capacity of 431.9 mAh g-1 at 0.5 A g-1 and remarkable cycling stability of 219.1 mAh g-1 at 20 A g-1 with 78 % capacity retention after 1500 cycles. The in-situ electrochemical impedance spectroscopy (EIS), in-situ X-ray diffraction (XRD), ex-situ X-ray photoelectron spectroscopy (XPS) and ex-situ high resolution transmission electron microscopy (HR-TEM) analysis investigate a highly reversible intercalation Zn-storage mechanism, and the enhanced the redox kinetics are related to the combined effect of interlayer regulation, high electronic conductivity and oxygen defect engineering by partial substitution NH4+ of PPy incorporation.

Clinical characteristics and outcomes of allogeneic hematopoietic stem cell transplantation recipients with coronavirus disease 2019 caused by the Omicron variant: a prospective, observational cohort study.

We aimed to describe the clinical characteristics, particularly the occurrence and risk factors of severe/critical illness, in allogeneic hematopoietic stem cell (allo-HSCT) recipients infected with coronavirus disease 2019 (COVID-19) caused by Omicron variant in an observational prospective study (n = 311). The median time from allo-HSCT to COVID-19 diagnosis was 8.5 months (range 0.8-106.1) months. Four patients (1.3%) were reported to be asymptomatic during Omicron variant infection, and 135 (43.4%) patients showed lower respiratory tract disease. Thirty-four (10.9%) patients were categorized into serious infection (severe illness n = 25; critical illness n = 9) and the median duration from COVID-19 diagnosis to serious infections was 6 days (range, 0-29) days. Thirteen (4.2%) and 6 (1.9%) patients required intensive care unit care and invasive mechanical ventilation, respectively. Receiving more than 1 type of immunosuppressive therapies at COVID-19 diagnosis was associated with severity and persistence of infection. Six patients (1.9%) died after diagnosis of COVID-19 infection. The 4-week probability of overall survival after COVID-19 diagnosis was 98.7%, which was 100% and 88.2% for non-serious and serious infection group (P < 0.001), respectively. Thus, we observed a relatively low serious infection and mortality rate in allo-HSCT recipients infected with COVID-19 caused by Omicron variant.

Molecular network analysis of 308 newly diagnosed HIV infection and 210 ART failure patients from rural counties in Sichuan.

BACKGROUND: Few studies on molecular epidemiology have studied people with newly diagnosed HIV infection and ART Failure Patients at the same time in rural China. With more serious HIV epidemic than in other provinces in China, Sichuan is an area suitable for this study. OBJECTIVE: To analyze the characteristics of HIV-1 molecular networks and factors related to network entry among newly diagnosed HIV infection and ART Failure Patients in three county-level cities (A, B, C) in Sichuan Province, to provide scientific basis for accurate prevention and control. METHODS: Nested PCR amplification method was used to amplify HIV-1 pol gene region of 530 blood samples, Sequencer 4.9 was used to edit, clean and splice the gene sequence, Bioedit correction, Fastree 2.1.8 and Figtree 1.4.2 to construct evolutionary tree and determine genotype. HyPhy2.2.4 and Cytoscape 3.6.1 software were used to construct molecular network. Logistic regression analysis was applied. RESULTS: 523(98.68%) pol sequences were obtained, and a total of 518 valid sequences with basic information came into the final analyses. A total of 6 genotypes were detected, namely CRF01_AE (320,61.78%), CRF07_BC (149,28.76%), B (30,5.79%), CRF08_BC (11, 2.12%), CRF55_01B (6, 1.16%) and C (2, 0.39%). 186 of 518(35.91%) sequences entered the network at a genetic distance of 0.8%, forming 42 propagation clusters. "High-risk transmitters"(connected with two and more) accounted for 21.62%. Logistic regression showed that≥50 years old (OR = 2.474) were more risky than 18-49 years old, CRF07_BC sub-type (OR = 0.174) were less risky than CRF01_AE sub-type, B sub-type (OR = 6.698) is higher risky than CRF01_AE sub-type, and District B (OR = 0.077) less risky than that of A city. CONCLUSION: The sources of HIV infection in rural Sichuan are diversified and complicated. The prevention and control of HIV infection in Sichuan Province should focus on strengthening the long-term dynamic detection of elderly population, B strain sub-type, and in City A.

Up-front autologous stem cell transplant in peripheral T-cell lymphoma patients achieving complete response after first-line treatment: A multicentre real-world analysis.

We conducted a retrospective, multicentre study to compare consolidation therapy with or without first-line autologous stem cell transplant (ASCT) for peripheral T-cell lymphoma (PTCL) patients in a real-world setting. We enrolled 347 PTCL patients who achieved complete response after first-line treatment. Of these, 257 received consolidation chemotherapy (non-ASCT group) and 90 received ASCT (ASCT group). Clinical outcomes were comparable between ASCT and non-ASCT groups. After propensity score matching, the 2-year cumulative incidence of treatment-related mortality and relapse remained similar between groups (1.9% vs. 2.0%, p = 0.985; 24.7% vs. 47.1%, p = 0.021). However, significant differences emerged in progression-free survival and overall survival probabilities. Within the T-cell lymphoma subgroup, ASCT patients exhibited favourable outcomes compared to non-ASCT patients: 2-year progression-free survival (73.4% vs. 50.8%, p = 0.024) and overall survival (92.1% vs. 73.5%, p = 0.021). Notably, no significant differences were observed for patients with NK/T-cell lymphoma. These real-world data suggest that up-front ASCT is a safe and effective consolidation option for PTCL patients in remission, particularly those with T-cell lymphoma.

Accurate resection of hilar cholangiocarcinoma using eOrganmap 3D reconstruction and full quantization technique.

BACKGROUND: For treatment of hilar cholangiocarcinoma (HCCA), the rate of radical resection is low and prognosis is poor, and preoperative evaluation is not sufficiently accurate. 3D visualization has the advantage of giving a stereoscopic view, which makes accurate resection of HCCA possible. AIM: To establish precise resection of HCCA based on eOrganmap 3D reconstruction and full quantification technology. METHODS: We retrospectively analyzed the clinical data of 73 patients who underwent HCCA surgery. All patients were assigned to two groups. The traditional group received traditional 2D imaging planning before surgery (n = 35). The eOrganmap group underwent 3D reconstruction and full quantitative technical planning before surgery (n = 38). The preoperative evaluation, anatomical classification of hilar hepatic vessels, indicators associated with surgery, postoperative complications, liver function, and stress response indexes were compared between the groups. RESULTS: Compared with the traditional group, the amount of intraoperative blood loss in the eOrganmap group was lower, the operating time and postoperative intestinal ventilation time were shorter, and R0 resection rate and lymph node dissection number were higher (P < 0.05). The total complication rate in the eOrganmap group was 21.05% compared with 25.71% in the traditional group (P > 0.05). The levels of total bilirubin, Albumin (ALB) , aspartate transaminase, and alanine transaminase in the eOrganmap group were significantly different from those in the traditional group (intergroup effect: F = 450.400, 79.120, 95.730, and 13.240, respectively; all P < 0.001). Total bilirubin, aspartate transaminase, and alanine transaminase in both groups showed a decreasing trend with time (time effect: F = 30.270, 17.340, and 13.380, respectively; all P < 0.001). There was an interaction between patient group and time (interaction effect: F = 3.072, 2.965, and 2.703, respectively; P = 0.0282, 0.032, and 0.046, respectively); ALB levels in both groups tended to increase with time (time effect: F = 22.490, P < 0.001), and there was an interaction effect between groups and time (interaction effect: F = 4.607, P = 0.004). In the eOrganmap group, there was a high correlation between the actual volume of intraoperative liver specimen resection and the volume of preoperative virtual liver resection (t = 0.916, P < 0.001). CONCLUSION: The establishment of accurate laparoscopic resection of hilar cholangiocarcinoma based on preoperative eOrganmap 3D reconstruction and full quantization technology can make laparoscopic resection of hilar cholangiocarcinoma more accurate and safe.

A Rapid and Accurate Quantitative Analysis of Cellulose in the Rice Bran Layer Based on Near-Infrared Spectroscopy.

Cultivating rice varieties with lower cellulose content in the bran layer has the potential to enhance both the nutritional value and texture of brown rice. This study aims to establish a rapid and accurate method to quantify cellulose content in the bran layer utilizing near-infrared spectroscopy (NIRS), thereby providing a technical foundation for the selection, screening, and breeding of rice germplasm cultivars characterized by a low cellulose content in the bran layer. To ensure the accuracy of the NIR spectroscopic analysis, the potassium dichromate oxidation (PDO) method was improved and then used as a reference method. Using 141 samples of rice bran layer (rice bran without germ), near-infrared diffuse reflectance (NIRdr) spectra, near-infrared diffuse transmittance (NIRdt) spectra, and fusion spectra of NIRdr and NIRdt were used to establish cellulose quantitative analysis models, followed by a comparative evaluation of these models' predictive performance. Results indicate that the optimized PDO method demonstrates superior precision compared to the original PDO method. Upon examining the established models, their predictive capabilities were ranked in the following order: the fusion model outperforms the NIRdt model, which in turn surpasses the NIRdr model. Of all the fusion models developed, the model exhibiting the highest predictive accuracy utilized fusion spectra (NIRdr-NIRdt (1st der)) derived from preprocessed (first derivative) diffuse reflectance and transmittance spectra. This model achieved an external predictive R2p of 0.903 and an RMSEP of 0.213%. Using this specific model, the rice mutant O2 was successfully identified, which displayed a cellulose content in the bran layer of 3.28%, representing a 0.86% decrease compared to the wild type (W7). The utilization of NIRS enables quantitative analysis of the cellulose content within the rice bran layer, thereby providing essential technical support for the selection of rice varieties characterized by lower cellulose content in the bran layer.

Research progress of biomaterials and innovative technologies in urinary tissue engineering.

Substantial interests have been attracted to multiple bioactive and biomimetic biomaterials in recent decades because of their ability in presenting a structural and functional reconstruction of urinary tissues. Some innovative technologies have also been surging in urinary tissue engineering and urological regeneration by providing insights into the physiological behavior of the urinary system. As such, the hierarchical structure and tissue function of the bladder, urethra, and ureter can be reproduced similarly to the native urinary tissues. This review aims to summarize recent advances in functional biomaterials and biomimetic technologies toward urological reconstruction. Various nanofirous biomaterials derived from decellularized natural tissues, synthetic biopolymers, and hybrid scaffolds were developed with desired microstructure, surface chemistry, and mechanical properties. Some growth factors, drugs, as well as inorganic nanomaterials were also utilized to enhance the biological activity and functionality of scaffolds. Notably, it is emphasized that advanced approaches, such as 3D (bio) printing and organoids, have also been developed to facilitate structural and functional regeneration of the urological system. So in this review, we discussed the fabrication strategies, physiochemical properties, and biofunctional modification of regenerative biomaterials and their potential clinical application of fast-evolving technologies. In addition, future prospective and commercial products are further proposed and discussed.

Unusual Hybrid Magnesium Storage Mechanism in a New Type of Bi2O2CO3 Anode.

Bismuth and bismuth-based compounds have been extensively studied as anodes as prospective candidates for rechargeable magnesium batteries (rMBs). However, the unsatisfactory magnesium-storage capability caused by the typical alloying reaction mechanism severely restricts the practical option for anodes in rMBs. Herein, polyaniline intercalated Bi2O2CO3 nanosheets are prepared by an effective interlayer engineering strategy to fine-tune the layer structure of Bi2O2CO3, achieving enhanced magnesium-storage capacity, rate performance, as well as long cycle life. Excitedly, a stepwise insertion-conversion-alloying reaction is aroused to stabilize the performance, which is elucidated by in/ex situ investigations. Moreover, first-principles calculations confirm that the coupling of Bi2O2CO3 and polyaniline not only increases the conductivity induced by the strong density of states and the interior self-built-in electric field but also significantly reduces the energy barrier of Mg shuttles. Our findings shed light on exploring new electrode materials with an appropriate working mechanism toward high-performance rechargeable batteries.

Preemptive interferon-α therapy could prevent relapse of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation: A real-world analysis.

Introduction: Measurable residual disease (MRD)-directed interferon-a treatment (i.e. preemptive IFN-α treatment) can eliminate the MRD in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, this study aimed to further assess its efficacy in a multicenter retrospective study in a real-world setting. Methods: A total of 247 patientswho received preemptive IFN-α treatment were recruited from 4 hospitals in China. The protocols for MRD monitoring mainly based on quantitative polymerase chain reaction [qPCR] and multiparameter flow cytometry [MFC]. Results: The median duration of IFN-α treatment was 56 days (range, 1-1211 days). The cumulative incidences of all grades acute graft-versus-host disease (aGVHD), all grades chronic graft-versus-host disease (cGVHD), and severe cGVHD at 3 years after IFN-α therapy were 2.0% (95% confidence interval [CI], 0.3-3.8%), 53.2% (95% CI, 46.8-59.7%), and 6.2% (95% CI, 3.1-9.2%), respectively. The cumulative incidence of achieving MRD negative state at 2 years after IFN-α treatment was 78.2% (95% CI, 72.6-83.7%). The 3-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 20.9% (95% CI, 15.5-26.3%) and 4.9% (95%CI, 2.0-7.7%), respectively. The probabilities of leukemia-free survival and overall survival at 3 years following IFN-α therapy were 76.9% (95% CI, 71.5-82.7%) and 84.2% (95% CI, 78.7-90.1%), respectively. Multivariable analysis showed that MRD positive state by qPCR and MFC before IFN-α treatment, high-risk disease risk index before allo-HSCT, and receiving identical sibling donor HSCT were associated with a higher risk of relapse and a poorer leukemia-free survival. Severe cGVHD was associated with an increased risk of non-relapse mortality. Discussion: Thus, real-world data suggest that preemptive IFN-α is effective for treating patients with AML with MRD after allo-HSCT.

Machine learning algorithm as a prognostic tool for Epstein-Barr virus reactivation after haploidentical hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) reactivation is one of the most important infections after hematopoietic stem cell transplantation (HSCT) using haplo-identical related donors (HID). We aimed to establish a comprehensive model with machine learning, which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. We enrolled 470 consecutive acute leukemia patients, 60% of them (n = 282) randomly selected as a training cohort, the remaining 40% (n = 188) as a validation cohort. The equation was as follows: Probability (EBV reactivation) =   1 1       +       e x p ( - Y ) , where Y = 0.0250 × (age) - 0.3614 × (gender) + 0.0668 × (underlying disease) - 0.6297 × (disease status before HSCT) - 0.0726 × (disease risk index) - 0.0118 × (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] score) + 1.2037 × (human leukocyte antigen disparity) + 0.5347 × (EBV serostatus) + 0.1605 × (conditioning regimen) - 0.2270 × (donor/recipient gender matched) + 0.2304 × (donor/recipient relation) - 0.0170 × (mononuclear cell counts in graft) + 0.0395 × (CD34+ cell count in graft) - 2.4510. The threshold of probability was 0.4623, which separated patients into low- and high-risk groups. The 1-year cumulative incidence of EBV reactivation in the low- and high-risk groups was 11.0% versus 24.5% (P < .001), 10.7% versus 19.3% (P = .046), and 11.4% versus 31.6% (P = .001), respectively, in total, training and validation cohorts. The model could also predict relapse and survival after HID HSCT. We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.

Non-Destructive Discrimination of Sunflower Seeds with Different Internal Mildew Grades by Fusion of Near-Infrared Diffuse Reflectance and Transmittance Spectra Combined with 1D-CNN.

Internally mildewed sunflower seeds, which cannot be recognized and discarded based on their appearance, pose a serious risk to human health. Thus, there is a need for a rapid non-destructive mildew grade discrimination method. Currently, few reports are available regarding this process. In this study, a method based on the combination of the near-infrared diffuse reflectance and near-infrared diffuse transmission (NIRr-NIRt) fusion spectra and a one-dimension convolutional neural network (1D-CNN) is proposed. The NIRr-NIRt fusion spectra can provide more complementary and comprehensive information, and therefore better discrimination accuracy, than a single spectrum. The first derivative (FD) preprocessing method could further improve the discrimination effect. By comparison against three conventional machine learning algorithms (artificial neural network (ANN), support vector machine (SVM), and K-nearest neighbor (KNN)), the 1D-CNN model based on the fusion spectra was found to perform the best. The mean prediction accuracy was 2.01%, 5.97%, and 10.55% higher than that of the ANN, SVM, and KNN models, respectively. These results indicate that the CNN model was able to precisely classify the mildew grades with a prediction accuracy of 97.60% and 94.04% for the training and test set, respectively. Thus, this study provides a non-destructive and rapid method for classifying the mildew grade of sunflower seeds with the potential to be applied in the quality control of sunflower seeds.

Effects of Variations in the Chemical Composition of Individual Rice Grains on the Eating Quality of Hybrid Indica Rice Based on Near-Infrared Spectroscopy.

The chemical composition of individual hybrid rice (F2) varieties varies owing to genetic differences between parental lines, and the effects of these differences on eating quality are unclear. In this study, based on a self-developed near-infrared spectroscopy platform, we explored these effects among a set of 143 hybrid indica rice varieties with different eating qualities. The single-grain amylose content (SGAC) and single-grain protein content (SGPC) models were established with coefficients of determination (R2) of 0.9064 and 0.8847, respectively, and the dispersion indicators (standard deviation, variance, extreme deviation, quartile deviation, and coefficient of variation) were proposed to analyze the variations in the SGAC and SGPC based on the predicted results. Our correlation analysis found that the higher the variation in the SGAC and SGPC, the lower the eating quality of the hybrid indica rice. Moreover, the addition of the dispersion indicators of the SGAC and SGPC improved the R2 of the eating quality model constructed using the composition-related physicochemical indicators (amylose content, protein content, alkali-spreading value, and gel consistency) from 0.657 to 0.850. Therefore, this new method proved to be useful for identifying high-eating-quality hybrid indica rice based on single near-infrared spectroscopy prior to processing and cooking.

Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment.

We aimed to identify the characteristics of immune reconstitution (IR) in patients who recovered from steroid-refractory acute graft-versus-host disease (SR-aGVHD) after basiliximab treatment. A total of 179, 124, 80, and 92 patients were included in the analysis for IR at 3, 6, 9, and 12 months, respectively, after haploidentical donor hematopoietic stem cell transplantation (HID HSCT). We observed that IR was fastest for monocytes and CD8+ T cells, followed by lymphocytes, CD3+ T cells, and CD19+ B cells and slowest for CD4+ T cells. Almost all immune cell subsets recovered comparably between patients receiving <5 doses and ≥5 doses of basiliximab. Most immune cell subsets recovered comparably between SR-aGVHD patients who recovered after basiliximab treatment and event-free HID HSCT recipients. Patients who recovered from SR-aGVHD after basiliximab treatment experienced satisfactory IR, which suggested that basiliximab may not have prolonged the negative impact on IR in these patients.

Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis.

Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and meta-analysis of ruxolitinib as treatment for SR-GVHD. In addition, we wanted to compare the efficacy and safety between children and adults with SR-GVHD. Overall response rate (ORR) after ruxolitinib treatment was chosen as the primary end point. Complete response rate (CRR), infection, myelosuppression, and overall survival (OS) were chosen as secondary end points. A total of 37 studies were included in this meta-analysis, and 1,580 patients were enrolled. ORR at any time after ruxolitinib treatment was 0.77 [95% confidence interval (CI): 0.68-0.84] and 0.78 (95% CI: 0.74-0.81), respectively, for SR-aGVHD and SR-cGVHD. CRR at any time after ruxolitinib treatment was 0.49 (95% CI: 0.40-0.57) and 0.15 (95% CI: 0.10-0.23), respectively, for SR-aGVHD and SR-cGVHD. The ORRs at any time after treatment was highest in mouth SR-cGVHD, followed by skin, gut, joints and fascia, liver, eyes, esophagus, and lung SR-cGVHD. The incidence rate of infections after ruxolitinib treatment was 0.61 (95% CI: 0.45-0.76) and 0.47 (95% CI: 0.31-0.63), respectively, for SR-aGVHD and SR-cGVHD. The incidence rates of overall (grades I-IV) and severe (grades III-IV) cytopenia were 53.2% (95% CI: 16.0%-90.4%) and 31.0% (95% CI: 0.0-100.0%), respectively, for SR-aGVHD, and were 28.8% (95% CI:13.0%-44.6%) and 10.4% (95% CI: 0.0-27.9%), respectively, for SR-cGVHD. The probability rate of OS at 6 months after treatment was 63.9% (95% CI: 52.5%-75.2%) for SR-aGVHD. The probability rates of OS at 6 months, 1 year, and 2 years after treatment were 95% (95% CI: 79.5%-100.0%), 78.7% (95% CI: 67.2%-90.1%), and 75.3% (95% CI: 68.0%-82.7%), respectively, for SR-cGVHD. The ORR, CRR, infection events, and myelosuppression were all comparable between children and adults with SR-GVHD. In summary, this study suggests that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults with SR-GVHD could benefit from ruxolitinib treatment.