Frontline combination of dasatinib and low-intensity chemotherapy in adults with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: Studies on dasatinib-based low-intensity induction regimens and post-remission strategies are limited in China. Therefore, we conducted a single-center phase 2 trial in newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) to establish the efficacy and safety of this treatment approach. RESEARCH DESIGN AND METHODS: Patients received one month of dasatinib plus low-intensity chemotherapy and two months of dasatinib monotherapy for induction, followed by a single course of high-dose methotrexate for consolidation. Subsequently, they underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or tyrosine kinase inhibitor (TKI)-based treatment for maintenance therapy between October 2015 and August 2022. RESULTS: Twenty-two patients were enrolled. Median age was 45 years (range, 20-71). The rates of major and complete molecular responses in the third month were 18.2% and 40.9% respectively. With a median follow-up of 15 months (range, 5-89), the estimated 3-year disease-free survival (DFS) and overall survival (OS) were 52.4% and 73.2%, respectively. The TKI-based cohort had a significantly poorer DFS (p = 0.014) and OS (p = 0.008) than the allo-HSCT cohort. CONCLUSIONS: Our results suggest that dasatinib-based low-intensity chemotherapy is safe and effective as an induction strategy in the Chinese population. Allo-HSCT plays a crucial role in the long-term outcomes of patients with Ph+ ALL. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as NCT02690922.

Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

A differential diagnosis method for systemic CAEBV and the prospect of EBV-related immune cell markers via flow cytometry.

Chronic active Epstein-Barr virus (CAEBV) infection of the T-cell or Natural killer (NK)-cell type, systemic form (systemic CAEBV or sCAEBV) was defined by the WHO in 2017 as an EBV-related lymphoproliferative disorder and is listed as an EBV-positive T-cell and NK-cell proliferation. The clinical manifestations and prognoses are heterogeneous. This makes systemic CAEBV indistinguishable from other EBV-positive T-cell and NK-cell proliferations. Early diagnosis of systemic CAEBV and early hematopoietic stem cell transplantation can improve patient prognosis. At present, the diagnosis of systemic CAEBV relies mainly on age, clinical manifestations, and cell lineage, incurring missed diagnosis, misdiagnosis, long diagnosis time, and inability to identify high-risk systemic CAEBV early. The diagnostic methods for systemic CAEBV are complicated and lack systematic description. The recent development of diagnostic procedures, including molecular biological and immunological techniques such as flow cytometry, has provided us with the ability to better understand the proliferation of other EBV-positive T cells and NK cells, but there is no definitive review of their value in diagnosing systemic CAEBV. This article summarizes the recent progress in systemic CAEBV differential diagnosis and the prospects of flow cytometry.

Recombinant Human Thrombopoietin Promotes Platelet Engraftment in Severe Aplastic Anemia Patients Following Treatment With Haploid Hematopoietic Stem Cell Transplantation using Modified Post-Transplantation Cyclophosphamide.

BACKGROUND: Recombinant human TPO (rhTPO) promotes platelet engraftment in patients after allogeneic HSCT (allo-HSCT). However, the effects of rhTPO on platelet recovery after Haplo-HSCT in patients with severe aplastic anemia (SAA) have not been intensively studied. OBJECTIVE: We aimed to evaluate the efficacy of rhTPO on platelet engraftment in patients with SAA who were treated with Haplo-HSCT using post-transplantation cyclophosphamide (PTCy). STUDY DESIGN: SAA patients who received Haplo-HSCT plus PTCy regimen were divided into the rhTPO group (with subcutaneous injection of rhTPO, n = 28) and Control group (no rhTPO administration, n = 27). The engraftment of platelet/neutrophil, platelet infusion amount, and transplant-related complications between the 2 groups were compared. RESULTS: All 55 patients showed successful hematopoietic reconstitution. The median time of platelet engraftment was 11 (9 to 29) days in the rhTPO group and 14 (9 to 28) days in the Control group (P = .003). The rhTPO group had a significantly reduced amount of infused platelets compared to the Control group (2 (1 to 11.5) versus 3 (1 to 14) therapeutic doses; P = .004). There was no significant difference between the 2 groups regarding median time of neutrophil engraftment, incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD), incidence of cytomegalovirus or Epstein-Barr virus reactivation, 3-yr overall survival rate, and failure-free-survival rate. No obvious adverse reactions were observed in the rhTPO group. CONCLUSION: rhTPO promoted platelet engraftment, reduced the amount of transfused platelets, and demonstrated good safety profiles without evidence of adverse reactions in patients with SAA who received Haplo-HSCT using PTCy regimen.

First report of Dactylonectria pauciseptata causing root rot on Eucalyptus cinerea in China.

Eucalyptus cinerea is an evergreen tree in the Myrtaceae. It is native to southern and eastern New South Wales and northern and eastern Victoria, Australia. It was introduced into China in the 1980s (Silva et al. 2011). Because of its unique shape, flexible stems, and rapid growth characteristics, it is widely used in the pulp industry and in decorative materials such as flower bouquets. In July 2022, 5- to 10-year-old E. cinerea showing symptoms of dehydration, withering and yellowing leaves, were found in forests and nurseries in Kunming and Songming, China. More than 37% of the trees showed these symptoms at each location, and disease severity was about 30%. Sixty symptomatic plants were collected from five tree nurseries. Diseased roots with 2-cm-long lesions were soaked in 75% ethanol for 15 s, 0.1% mercuric chloride for 2 min, rinsed with sterilized water, and placed on potato dextrose agar (PDA) at 25℃ for 3 days. Thirty samples were plated, and 21 isolates (YJLGF01 to YJLGF21) obtained, 11 strains with similar colony morphology (including representative strains YJLGF03 to YJLGF05). Three isolates (YJLGF03 to YJLGF05) were obtained by single-spore purification. On PDA, the colonies were circular with fluffy white to light yellow mycelium; the underside was yellowish brown. Conidiophores were bifurcated, with macroconidia borne terminally. The macroconidia were cylindrical with rounded, blunt ends, yellow to transparent, 1 to 3 septate (22.5 to 47.6 × 4.5 to 7.1 µm); microconidia were 0 to 1 septate (12.5 to 19.6 × 4.7 to 6.4 µm). Chlamydospores were spherical, rosary-like, and light yellow. Morphological characteristics were consistent with published descriptions of Dactylonectria pauciseptata (Piperkova et al. 2017). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1- alpha (ef1-α) gene, and the beta-tubulin 2 (ß-tub2) gene were amplified and sequenced (ITS accessions OR735053, OR735054, OR735055; ß-tub2 accessios OR757447, OR757448, OR757449; ef1-α accessions OR757450, OR757451, OR757451) using published primers (White et al. 1990; Carbone et al. 1999). A phylogenetic tree was developed by Maximum Parsimony (MP) and Maximum Likelihood (ML) methods. These three isolates fell into the D. pauciseptata clade and were distinguished clearly from other species. Pathogenicity tests were performed using the same three isolates. Each isolate was cultured on PDA, and then subcultured in V8 juice broth on an orbital shaker at 180 RPM for 5 days. Conidia were collected by centrifugation at 6,000 RPM for 5 min, and then resuspended in sterilized distilled water (1×106 conidia/ml). Injured roots of one-year-old E. cinerea were soaked in the spore suspension for 1 h before being transplanted in sterile vermiculite. The plants were incubated at 25℃ with a 12 h photoperiod and 90% humidity. Five plants were inoculated as a group for each treatment and the entire experiment was completed three times. Among the inoculated plants, the incidence of disease development was 100%. A small sot appeared after 4 days, with a water-soaked lesion appearing and gradually expanding during days 5 to 7. After 10 days symptoms of root necrosis were similar to the those observed in the nursery, and aboveground plant parts had yellow, withering leaves and defoliation after 10 to 15 days. Control plants treated with sterile water showed no disease symptoms. The three strains were successfully reisolated from inoculated seedlings and confirmed them using DNA sequencing. No isolates were obtained from the control plants, thus fulfilling Koch's postulates. Dactylonectria pauciseptata was first reported from necrotic tissue of infected grape roots (Schroers et al. 2008). So far, it has been reported in Turkey, Canada, Brazil, Italy, and other countries (Erper et al. 2013; Úrbez-Torres et al. 2014; Santos et al. 2014). Based on our results, E. cinerea is a new host plant of D. pauciseptata in China. This disease is a threat to the nursery production of E. cinerea, potentially leading to a reduction in yields and economic losses.

EBV-associated lymphoproliferative disease post-CAR-T cell therapy.

Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell therapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median time of 38.5 months after CAR-T cell therapy, B-cell-derived EBV-LPDs were diagnosed, and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents. Collectively, our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders, and they can be resolved by immune normalization strategy or B-cell depleting therapy.

Research on blasting mechanism and blasting effect of aqueous media in open pit coal mines.

Surface coal mining procedures include piercing-blasting-mining and loading-transportation-discharging, blasting link exists due to the poor blasting effect leads to low loading efficiency, blasting dust caused by environmental pollution and other problems. In this paper, from the mechanical characteristics of the water medium, we analyze in detail the transferring effect, transducing effect and bubble pulsation phenomenon of the water medium in the blasting process. The results show that when the blasting medium is water medium, the maximum principal stress is 1.53 times that of air medium; the peak energy transfer can be up to 2.73 times that of air medium. With the help of TrueGrid/LS-DYNA finite element analysis software to simulate the dynamic process of blasting, the study of the maximum principal stresses around the hole, the top of the slope, the foot of the slope on the maximum principal stress changes, the results show that the maximum principal stresses around the hole, the top of the slope, the foot of the slope unit with the increase in the water content is gradually increasing trend. Finally, combined with the actual mine production conditions for blasting field test, water-mediated blasting dust reduction rate of 75%, the use of AHP-fuzzy comprehensive evaluation method of two groups of traditional dry hole blasting and three groups of water-mediated blasting comprehensive evaluation, the results show that the water-mediated blasting scores are higher than the traditional dry hole blasting, proving that the water-mediated blasting has a certain prospect of engineering applications.

Impact of sarcopenia on the survival of patients undergoing liver transplantation for decompensated liver cirrhosis.

BACKGROUND: Patients with decompensated cirrhosis (DC) are prone to skeletal muscle loss, namely, sarcopenia, before liver transplantation (LT). While sarcopenia is reportedly associated with adverse outcomes after LT, these findings are limited owing to mixed diseases and retrospective data. We investigated the association between sarcopenia and 1-year overall survival (OS) in patients with DC after LT and established and validated a prediction model for postoperative OS based on sarcopenia. METHODS: Overall, 222 consecutive patients who underwent LT at our centre were registered between September 2020 and June 2022. Third lumbar spine skeletal muscle mass index was measured using computed tomography. Patients were divided into sarcopenia and non-sarcopenia groups according to the skeletal muscle mass index, and baseline data and postoperative outcomes were collected, compared and analysed. The primary outcome was the 1-year OS after LT. We established a dynamic nomogram of the OS predictive model. RESULTS: We included 177 DC patients [mean (standard deviation) age, 50.2 ± 9.3 years; 52 women (29.4%)]; 73 (41.2%) had sarcopenia. The mean (standard deviation) body mass index was 22.6 ± 4.5 kg/m2 , 28 (15.8%) patients had weight loss ≥5% within 6 months before admission, and the mean (standard deviation) model for end-stage liver disease (MELD) score was 18.4 ± 7.9. Patients with sarcopenia had a longer duration of intensive care unit stay (4.1 ± 2.2 vs. 3.1 ± 1.1 days, P = 0.008), higher rate of major complications (45.2% vs. 22.1%, P = 0.001) and higher postoperative mortality (15.1% vs. 2.9%, P = 0.003) than those without sarcopenia. The median 1-year OS after surgery was shorter in patients with sarcopenia than in those without (P < 0.001). Sarcopenia [hazard ratio (HR), 2.54; 95% confidence interval (CI), 1.54-5.63; P = 0.022], weight loss ≥5% (HR, 2.46; 95% CI, 1.39-5.09; P = 0.015) and MELD score (HR, 1.05; 95% CI, 1.01-1.09; P = 0.009) were independent risk factors associated with 1-year OS. The area under the curve of the established dynamic nomogram was 0.774, the calibration curve showed good consistency, and analysis of the decision curve showed more clinical benefits than the MELD score alone. High-risk patients (>102.9 points calculated using the nomogram) had a significantly reduced survival rate. CONCLUSIONS: Sarcopenia is associated with adverse outcomes after LT in patients with DC. High-risk patients should be classified by dynamic nomogram upon admission.

Identification of the novel allele, HLA-B*48:58, in a patient with chronic myelogenous leukemia.

HLA-B*48:58 differs from HLA-B*48:01:01 by one nucleotide substitution in codon 17 in exon 2.

Real-world experience with selinexor-containing chemotherapy-free or low-dose chemotherapy regimens for patients with relapsed/refractory acute myeloid leukemia and myeloid sarcoma.

Introduction: Treatment of relapsed or refractory acute myeloid leukemia (R/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of R/R AML have demonstrated promising results. This study aimed to evaluate the efficacy and safety of chemotherapy-free or low-dose chemotherapy regimens with selinexor for R/R AML and MS patients. Methods: Ten patients with R/R AML or MS who received chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor at Tongji Hospital from October 2021 to August 2022 were included in this study. The primary endpoint was overall response rate (ORR) and secondary endpoints included complete remission (CR), CR with incomplete hematological recovery (CRi), partial remission (PR), transplantation rate, and safety. Results: All patients were evaluable for response, achieving CR in four (40.0%) patients and CRi in two (20.0%) patients for a total CR/CRi of 60.0%. The ORR was 80.0% when patients with PR were included. Five (50.0%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after treatment with selinexor-containing regimens. At the end of the follow-up, seven (70.0%) patients were alive, and three patients died of transplant-related complications or disease progression. The most frequently reported nonhematologic adverse events (AEs) in patients were grade 1 or 2 asymptomatic hyponatremia. Conclusion: The chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor for R/R AML are feasible and tolerable and provide an opportunity for patients to receive transplantation.

Comparison of haploidentical-allogeneic hematopoietic stem cell transplantation and intensive immunosuppressive therapy for patients with severe aplastic anemia with an absolute neutrophil count of zero: a retrospective study.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical-allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0% vs. 40.0%, P = 0.001; 80.0% vs. 17.1%, P = 0.001). With a median follow-up of 18.5 months (4.3~30.8 months), patients in the HID-HSCT group had longer overall survival and event-free survival (80.0% vs. 47.9%, P = 0.0419; 79.2% vs. 33.5%, P = 0.0048). These data suggested that HID-HSCT might be an effective alternative treatment option for adult patients with SAA with an ANC of zero, which requires further validation in an additional prospective study.

Development of a model by LASSO to predict hospital length of stay (LOS) in patients with the SARS-Cov-2 omicron variant.

The length of stay (LOS) in hospital varied considerably in different patients with COVID-19 caused by SARS-CoV-2 Omicron variant. The study aimed to explore the clinical characteristics of Omicron patients, identify prognostic factors, and develop a prognostic model to predict the LOS of Omicron patients. This was a single center retrospective study in a secondary medical institution in China. A total of 384 Omicron patients in China were enrolled. According to the analyzed data, we employed LASSO to select the primitive predictors. The predictive model was constructed by fitting a linear regression model using the predictors selected by LASSO. Bootstrap validation was used to test performance and eventually we obtained the actual model. Among these patients, 222 (57.8%) were female, the median age of patients was 18 years and 349 (90.9%) completed two doses of vaccination. Patients on admission diagnosed as mild were 363 (94.5%). Five variables were selected by LASSO and a linear model, and those with P < 0.05 were integrated into the analysis. It shows that if Omicron patients receive immunotherapy or heparin, the LOS increases by 36% or 16.1%. If Omicron patients developed rhinorrhea or occur familial cluster, the LOS increased by 10.4% or 12.3%, respectively. Moreover, if Omicron patients' APTT increased by one unit, the LOS increased by 0.38%. Five variables were identified, including immunotherapy, heparin, familial cluster, rhinorrhea, and APTT. A simple model was developed and evaluated to predict the LOS of Omicron patients. The formula is as follows: Predictive LOS = exp(1*2.66263 + 0.30778*Immunotherapy + 0.1158*Familiar cluster + 0.1496*Heparin + 0.0989*Rhinorrhea + 0.0036*APTT).

ROS-scavenging hydrogel as protective carrier to regulate stem cells activity and promote osteointegration of 3D printed porous titanium prosthesis in osteoporosis.

Stem cell-based therapy has drawn attention as an alternative option for promoting prosthetic osteointegration in osteoporosis by virtue of its unique characteristics. However, estrogen deficiency is the main mechanism of postmenopausal osteoporosis. Estrogen, as an effective antioxidant, deficienncy also results in the accumulation of reactive oxygen species (ROS) in the body, affecting the osteogenic differentiation of stem cells and the bone formation i osteoporosis. In this study, we prepared a ROS-scavenging hydrogel by crosslinking of epigallocatechin-3-gallate (EGCG), 3-acrylamido phenylboronic acid (APBA) and acrylamide. The engineered hydrogel can scavenge ROS efficiently, enabling it to be a cell carrier of bone marrow-derived mesenchymal stem cells (BMSCs) to protect delivered cells from ROS-mediated death and osteogenesis inhibition, favorably enhancing the tissue repair potential of stem cells. Further in vivo investigations seriously demonstrated that this ROS-scavenging hydrogel encapsulated with BMSCs can prominently promote osteointegration of 3D printed microporous titanium alloy prosthesis in osteoporosis, including scavenging accumulated ROS, inducing macrophages to polarize toward M2 phenotype, suppressing inflammatory cytokines expression, and improving osteogenesis related markers (e.g., ALP, Runx-2, COL-1, BSP, OCN, and OPN). This work provides a novel strategy for conquering the challenge of transplanted stem cells cannot fully function in the impaired microenvironment, and enhancing prosthetic osteointegration in osteoporosis.

Prolonged use of eltrombopag in patients with severe aplastic anemia in the real world.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months.Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months.At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31%, 61%, 82% and 90%, and the cumulative CR rates were 0, 14%, 27% and 45%, respectively. The cumulative effect curve showed that 93% and 53% of all remission and CR occurred within 6 months, while 98% and 83% of all remission and CR occurred within 12 months. Thirty-seven percent of patients (11 of 30) with partial remission (PR) at 6 months continuously exposed to EPAG improved to CR within 3 (1-5) months of the extended median time. Six patients failing at 6 months continued to use EPAG. Three patients showed improved responses with an extended median time of 6 (1-6) months. The 2-year event-free survival (EFS) was better in those continuing with EPAG (89% vs. 49%, P = 0.006) for patients with PR or non-remission at 6 months.Continuous administration with EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months.This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2100045895).

Cladribine- and decitabine-containing conditioning regimen has a low post-transplant relapse rate in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome.

To reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there have been continuing efforts to optimize the conditioning regimens. Our study aimed to analyze the risk factors associated with the relapse of relapsed/refractory (R/R), high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) post-transplant and the efficacy of a new conditioning regimen involving decitabine and cladribine. Clinical data of 125 patients with R/R AML, high-risk AML and high-risk MDS who underwent allo-HSCT were collected. In addition, 35 patients with R/R AML, high-risk AML and high-risk MDS received treatment with a new conditioning regimen including decitabine and cladribine. Cox regression analysis was used to identify risk factors associated with OS, RFS and relapse. Among 125 patients who underwent allo-HSCT, CR before allo-HSCT and matched sibling donors were independent protective factors for OS. DNMT3A abnormality was an independent risk factor for both relapse and RFS. Among 35 patients who received a new conditioning regimen containing decitabine and cladribine, only six patients relapsed and 1-year cumulative incidence of relapse was 11.7%. Moreover, this new regimen showed efficient MRD clearance early after allo-HSCT. The combined decitabine- and cladribine-based conditioning regimen showed a low relapse rate and a high survival without an increased incidence of GVHD or adverse effects and thus has potential for use in allo-HSCT for R/R AML, high-risk AML and high-risk MDS.

The effects of bicarbonated versus acetated Ringer's solutions on acid-base status and kidney injury following orthotopic liver transplantation: Protocol for a single-centre, randomised controlled trial (The BETTER trial).

Background: The ideal crystalloid fluid of choice for fluid therapy during liver transplantation is unknown. Conventional balanced crystalloids are buffered with organic anions, which requires liver metabolism to prevent matabolic acidosis and protect renal function. Therefore they can not function properly during liver transplantation. On the contrary, the bicarbonated Ringer's solution (BRS) can maintain acid-base status regardless of liver function. In this study, we aimed to test the hypothesis that, in patients undergoing orthotopic liver transplantation, compared with acetated Ringer's solutions (ARS), perioperative fluid therapy with BRS could better maintain the acid-base status. Methods: This is a prospective, single-centre, randomised controlled trial. 72 eligible patients will be randomised to receive either BRS or ARS perioperatively. The primary endpoint is the difference in standard base excess (SBE) before and after operation. Secondary endpoints include the incidence of acute kidney injury (AKI) within 48 h post operation and free and alive days to day 14 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy (RRT). Discussion: Metabolic acidosis is common perioperatively, potentially leading to decreased renal blood flow and reduced glomerular filtration rate. The use of balanced solutions can prevent hyperchloremic metabolic acidosis, thereby avoiding AKI in some patients. However, during liver transplantation, when well-functioning liver metabolism is lacking, the organic anions in conventional balanced solutions may remain strong anions and thus fail to maintain the acid-base status, but no solid clinical evidence exists now. This study will, for the first time, provide evidence on the relative effects of BRS vs. ARS on acid-base status and renal injury in patients undergoing liver transplantation. Clinical Trial Registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100046889) on 29 May 2021.

Comparison of clinical characteristics between SARS-CoV-2 Omicron variant and Delta variant infections in China.

Background: The continued 'evolution' of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence of the Omicron variant after the Delta variant, resulting in a significant increase in the number of people with COVID-19. This increase in the number of cases continues to have a significant impact on lives. Therefore, a more detailed understanding of the clinical characteristics of Omicron infection is essential. Methods: Using medical charts, we extracted clinical information for 384 patients infected with the Omicron variant in Anyang City, Henan Province, China. Epidemiology and clinical characteristics were compared with a cohort of people infected with the Delta variant in Zhengzhou in 2021. Findings: Common initial symptoms at onset of illness were cough [240 (63%)], expectoration [112 (29%)], fever [96 (25%)], nasal congestion [96 (25%)] and myalgia or fatigue [30 (6%)]. In patients with the Omicron variant, levels of total cholesterol, low-density lipoprotein and creatinine increased in 52 (14%), 36 (9%) and 58 (15%) patients, respectively, compared with patients with the Delta variant [one (1%), one (1%) and two (2%)]. Levels of triglyceride and high-density lipoprotein also increased. In patients with the Omicron variant, the levels of specific gravity and the erythrocyte sedimentation rate were increased in 115 (30%) and 81 (21%) patients, and serum levels of complement 3 decreased in 93 (41%). Results: Compared with patients infected with Delta, no major differences in initial clinical symptoms were identified in patients infected with Omicron. However, dyslipidemia and kidney injury were much more severe in patients with the Omicron variant, and the erythrocyte sedimentation rate was increased. Due to decreased levels of complement 3, the immunity of patients with the Omicron variant was weak.

A real-word experience of eltrombopag plus rabbit antithymocyte immunoglobulin-based IST in Chinese patients with severe aplastic anemia.

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, the effects of real-life use of low doses of EPAG combined with rabbit antithymocyte globulin (ATG)-based IST in Asian patients with SAA are yet unknown. A total of 121 previously untreated Chinese patients with SAA were enrolled in a multicenter registry of the Chinese Eastern Collaboration Group of Anemia (2014-2020): 67 patients received IST alone and 54 patients received additional EPAG. Patients receiving IST plus EPAG had a higher overall response rate (ORR) at 1 month (P = 0.002), 3 months (P = 0.028), 6 months (P = 0.006), and 12 months (P = 0.031) compared to those receiving IST alone. EPAG was the favorable factor for response efficacy at 6 months. The complete response rate in the EPAG plus IST group was 17% at 3 months, 27% at 6 months, and 32% at 12 months, compared to 7% (P = 0.069), 14% (P = 0.11), and 33% (P = 0.92) for those treated with IST alone. The 2-year overall survival rate in EPAG plus IST and IST alone groups was 98% and 88%, respectively (P = 0.078). The rate of adverse events, including clonal evolution, infection, and transaminitis, was similar in the two cohorts. The addition of EPAG to IST was well-tolerated and associated with high rates of hematologic responses among the previously untreated Chinese patients with SAA.