An updated HACOR score for predicting the failure of noninvasive ventilation: a multicenter prospective observational study.

BACKGROUND: Heart rate, acidosis, consciousness, oxygenation, and respiratory rate (HACOR) have been used to predict noninvasive ventilation (NIV) failure. However, the HACOR score fails to consider baseline data. Here, we aimed to update the HACOR score to take into account baseline data and test its predictive power for NIV failure primarily after 1-2 h of NIV. METHODS: A multicenter prospective observational study was performed in 18 hospitals in China and Turkey. Patients who received NIV because of hypoxemic respiratory failure were enrolled. In Chongqing, China, 1451 patients were enrolled in the training cohort. Outside of Chongqing, another 728 patients were enrolled in the external validation cohort. RESULTS: Before NIV, the presence of pneumonia, cardiogenic pulmonary edema, pulmonary ARDS, immunosuppression, or septic shock and the SOFA score were strongly associated with NIV failure. These six variables as baseline data were added to the original HACOR score. The AUCs for predicting NIV failure were 0.85 (95% CI 0.84-0.87) and 0.78 (0.75-0.81) tested with the updated HACOR score assessed after 1-2 h of NIV in the training and validation cohorts, respectively. A higher AUC was observed when it was tested with the updated HACOR score compared to the original HACOR score in the training cohort (0.85 vs. 0.80, 0.86 vs. 0.81, and 0.85 vs. 0.82 after 1-2, 12, and 24 h of NIV, respectively; all p values < 0.01). Similar results were found in the validation cohort (0.78 vs. 0.71, 0.79 vs. 0.74, and 0.81 vs. 0.76, respectively; all p values < 0.01). When 7, 10.5, and 14 points of the updated HACOR score were used as cutoff values, the probability of NIV failure was 25%, 50%, and 75%, respectively. Among patients with updated HACOR scores of ≤ 7, 7.5-10.5, 11-14, and > 14 after 1-2 h of NIV, the rate of NIV failure was 12.4%, 38.2%, 67.1%, and 83.7%, respectively. CONCLUSIONS: The updated HACOR score has high predictive power for NIV failure in patients with hypoxemic respiratory failure. It can be used to help in decision-making when NIV is used.

Clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension secondary to congenital portosystemic shunts.

The aim of this retrospective study was to investigate the clinical characteristics and therapeutic outcomes of pulmonary arterial hypertension (PAH) secondary to congenital portosystemic shunts (CPSS). Thirty-three pediatric patients diagnosed in our institution with CPSS between 2012 and 2019 were enrolled in this study. The patients were divided into PAH and non-PAH groups. The PAH group included 15 patients who presented with unexplained PAH when CPSS was diagnosed. Two patients with microangiopathic hemolytic anemia died of right heart failure shortly after diagnosis. One patient received a liver transplant at the age of 4.3 years and showed a mild decrease in pulmonary artery pressure (PAP) 4 years after the operation. Seven patients underwent one-stage shunt closure at a median age of 2.8 years (1.4-13 years). Follow-up examinations, from 1.6 to 4.1 years after intervention, showed marked reduction of PAP in one patient and stabilization of PAH in six others. However, in one patient who underwent two-stage shunt closure, a marked increase in PAP was noted after partial ligation of the shunt. The remaining four patients received only pulmonary vasodilator therapy, and one of them died of right heart failure 12 years after the PAH diagnosis. The non-PAH group included 18 patients without evidence of PAH upon CPSS diagnosis. Shunt closure was carried out in eight of these patients, but one patient subsequently developed PAH after the resolution of hepatopulmonary syndrome.Conclusion: CPSS may be a more likely cause of unexplained PAH in pediatric patients than previously thought. Shunt closure or liver transplantation may prevent the progression of PAH, or even improve it for the majority of CPSS patients.

Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet-Fed Mice through Increased Thermogenesis.

BACKGROUND: Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. OBJECTIVES: In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)-fed obese mice. METHODS: The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. RESULTS: After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. CONCLUSIONS: Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

Diurnal change in psychological and physiological responses to consistent relative humidity.

Diurnal changes in physiological and psychological responses to consistent relative humidity (RH) conditions were investigated in the present study. Lightly clothed six male and six female subjects participated in the first experiment at 40% and 50% RH, and seven male and seven female subjects participated in the second experiment at 60%, 70%, and 80% RH. Both experiments were conducted at 28 °C air temperature (Ta) from 9:00-18:30. Skin temperatures, local heat flux rates and tympanic temperature (Tty) were monitored at 2-min intervals throughout the experimental period. Body weight loss and oxygen consumption rate were measured during the 9:30-10:30, 13:30-14:30, and 17:30-18:30 periods. Thermal sensation and thermal comfort responses were recorded at the same periods. The amount of heat loss was greater than metabolic heat production (M) in the male subjects but was well balanced with M in the female subjects. A morning increase in Tty at 50%-80% RH was observed, and mean skin temperature (T‾sk) at 70% and 80% RH was significantly higher (p < 0.05) than Tsk at 40% and 50% RH in both subject groups. Although difference in the relationship between thermal sensation and T‾sk based on sex was confirmed, diurnal changes in thermal sensation were observed in both subject groups based on the responses of "warm" in the morning but "neutral" or "slightly warm" in the evening at 70% and 80% RH. This result demonstrates that high RH may be acceptable in the late afternoon and evening at 28 °C and indicates that dynamic control of RH during the daytime (e.g., low RH in the morning and high RH in late afternoon) may be beneficial to save energy when using air-conditioning.

Selenium decreases methylmercury and increases nutritional elements in rice growing in mercury-contaminated farmland.

Methylmercury (MeHg) in rice grains grown in Hg-contaminated areas has raised environmental health concerns. Pot experiments found that selenium (Se) could reduce MeHg levels in rice grains. However, relatively high levels of Se (up to 6 mg/kg) were applied in these pot experiments, which may have adverse effects on the soil ecology due to the toxicity of Se. The aims of this work were thus to study 1) the effect of low levels of Se on the accumulation and distribution of Hg, especially MeHg, in rice plants grown in a real Hg-contaminated paddy field and 2) the effect of Se treatment on Se and other nutritional elements (e.g., Cu, Fe, Zn) in grains. A field study amended with different levels of Se was carried out in Hg-contaminated paddy soil in Qingzhen, Guizhou, China. The levels of MeHg and total Hg were studied using cold vapor atomic fluorescence spectrometry (CVAFS) and inductively coupled plasma mass spectrometry (ICP-MS). The distribution and relative quantification of elements in grains were examined by synchrotron radiation X-ray fluorescence analysis (SR-XRF). This field study showed that low levels of Se (0.5 µg/mL, corresponding to 0.15 mg Se/kg soils) could significantly reduce total Hg and MeHg in rice tissues. Se treatment also reduced Hg distribution in the embryo and endosperm and increased the levels of Fe, Cu, Zn and Se in grains and especially embryos. This field study implied that treatment with an appropriate level of Se is an effective approach to not only decrease the level of MeHg but to also increase the levels of nutritional elements such as Fe, Cu, Zn and Se in rice grains, which could bring beneficial effects for rice-dependent residents living in Hg-contaminated areas.

Hypoxia-inducible factor-2α promotes hepatocyte apoptosis during cholestasis.

AIM: Hypoxia-inducible factor-2α (HIF-2α) has been reported to play an important role in a host of pathophysiological processes, including cellular survival. This study explores the role of HIF-2α in cholestasis-mediated hepatocyte apoptosis. METHODS: Hypoxia-inducible factor-2α expression was measured by immunohistochemistry and confocal microscopy. Hepatic apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling. The cholestatic mouse model was treated with bile duct ligation. The c-myc, p53, and Bax protein levels were measured with Western blot analysis. RESULTS: In pediatric and murine cholestatic liver tissues, HIF-2α protein was widely expressed in the nucleus of parenchymal cells as well as in stromal cells. Hepatocyte HIF-2α expression was significantly elevated at the early stage of pediatric cholestasis and decreased at the late stage. In both in vivo and in vitro murine studies, HIF-2α deletion could alleviate cholestasis-mediated hepatocyte apoptosis and regulate the expression of c-myc, p53, and Bax proteins. CONCLUSION: These findings implied the contribution of HIF-2α to cholestasis-mediated hepatocyte apoptosis.

Expression of fibroblast growth factor 21 in patients with biliary atresia.

Fibroblast growth factor 21 is a critical circulating adipokine involving in metabolic disorders and various liver diseases. This study was performed to investigate whether FGF21 is also associated with the pathophysiology of biliary atresia. Serum FGF21 levels were measured in 57 BA patients and 20 age matched healthy controls. We also examined hepatic FGF21 mRNA expression and FGF21 protein levels in liver tissues obtained from 15 BA patients undergoing liver transplantation and 5 cases of pediatric donation after cardiac death donor without liver diseases by RT-PCR and Western blotting. Patients with BA showed significantly higher serum FGF21 levels than those without BA (554.7pg/mL [83-2300] vs. 124.5pg/mL [66-270], P<0.05). Patients with BA also had significantly higher FGF21 mRNA and protein levels in hepatic tissues than control subjects. Serum FGF21 expression increased corresponding to the severity of liver fibrosis. Furthermore, serum FGF21 levels dropped significantly in BA patients within 6months after liver transplantation and approached baseline in healthy controls (P>0.05). In vivo, FXR knockout could significantly abrogate cholestasis induced FGF21 expression. FGF21 levels in serum and liver tissue increased significantly in BA patients. In vivo, cholestasis could induce FGF21 expression in FXR dependent manner.

Congenital extrahepatic portosystemic shunt: an underdiagnosed but treatable cause of hepatopulmonary syndrome.

Congenital extrahepatic portosystemic shunt (CEPS) is a rare malformation of the mesenteric vasculature, which may lead to severe complications. In this report, we describe a case series of three children with type II CEPS (presenting as hypoxemia) and hepatopulmonary syndrome (HPS). The first patient was a 4-year-old male who did not receive any specific treatment and subsequently died of brain abscess 5 years after the diagnosis. The second patient was a 10-year-old female with a 5-year history of cyanosis and dyspnea on exertion. She had partial regression of hypoxemia and improved exercise tolerance at 8 months after a surgical shunt closure. The third patient was a 4-year-old male with a 3-year history of cyanosis and decreased exercise tolerance. He had full regression of hypoxemia at 3 months after a transcatheter shunt closure. CONCLUSION: These results indicate that CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences. Closure of portosystemic shunts may result in resolution of HPS in type II CEPS and the length of period for resolution varies depending on the severity of HPS. WHAT IS KNOWN: Congenital extrahepatic portosystemic shunt (CEPS) is a rare cause of hepatopulmonary syndrome (HPS). There have been few reports in the literature about the management and outcome of HPS in children with CEPS. WHAT IS NEW: CEPS may present in children with unexplained hypoxemia, which may lead to devastating clinical consequences. Closure of portosystemic shunts may result in resolution of HPS in type II CEPS.

Influence of graft size matching on outcomes of infantile living donor liver transplantation.

We aimed to assess the impact of size mismatching between grafts and recipients on outcomes of infants or small children after LDLT. Between October 2006 and December 2014, 129 LDLT recipients weighing no more than 8 kg were retrospectively analyzed. The entire cohort was categorized into three groups by GRWR: GRWR < 3.0% (group A, n = 38), 3.0% ≤ GRWR < 4.0% (group B, n = 61), and GRWR ≥ 4.0% (group C, n = 30). Baseline characteristics were similar among groups A, B, and C. Compared with groups A and B, post-transplant alanine aminotransferase and aspartate aminotransferase within seven days were significantly higher in group C; however, differences between total bilirubin and albumin after transplantation were not prominent. Moreover, incidences of surgical complications, perioperative deaths, infections, and acute rejections were all comparable among the three groups. Five-yr patient survival rates for groups A, B, and C were 89.5%, 88.9%, and 81.6%, respectively (p = 0.872), and the graft survival rates were 89.5%, 86.6%, and 81.6%, respectively (p = 0.846). In conclusion, GRWR between 1.9% and 5.8% would not cause noticeable adverse events for infantile LDLT recipients ≤ 8 kg. However, there is still a role for considering reduction in the graft mass as an applicable strategy in selected cases.

[Effect of different durations of prone ventilation on the efficacy of patients with acute respiratory distress syndrome: a small Meta-analysis].

OBJECTIVE: To systematically evaluate the effect of different durations of prone ventilation on the efficacy of patients with acute respiratory distress syndrome (ARDS). METHODS: A computer search was conducted in databases including PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database, and China Biomedical Literature Database for studies on prone ventilation for the treatment of adult patients with ARDS published from the establishment of the database to September 2023. Studies were categorized into ≤ 24 hours group and > 24 hours group based on the duration of prone ventilation. Outcome indicators included mortality, the length of intensive care unit (ICU) stay, incidence of pressure ulcers, and operation of tracheotomy. Two researchers independently screened the literature, extracted information, and evaluated the risk of bias of the included literature. The quality of the included literature was assessed using the NOS scale, and the effect of different durations of prone ventilation on the efficacy of ARDS was analyzed by Meta-analysis. RESULTS: A total of 517 patients from 4 papers were finally included, including 249 patients with prone ventilation duration ≤ 24 hours and 268 patients with prone ventilation duration > 24 hours. All 4 studies were cohort studies, and the overall inclusion of literature assessed for methodological quality indicated high study quality and low risk of bias. Meta-analysis showed that there were no significantly differences in mortality [relative risk (RR) = 1.02, 95% confidence interval (95%CI) was 0.79 to 1.31, P = 0.88], the length of ICU stay [mean difference (MD) = -2.68, 95%CI was -5.30 to - 0.05, P = 0.05] between the prone ventilation duration ≤ 24 hours group and prone ventilation duration > 24 hours group. Compared with the prone ventilation duration ≤24 hours group, the incidence of pressure ulcers (RR = 0.76, 95%CI was 0.59 to 0.98, P = 0.04) and the operation of tracheotomy (RR = 0.71, 95%CI was 0.53 to 0.94, P = 0.02) were significantly increased in the prone ventilation duration > 24 hours group. CONCLUSIONS: The duration of prone ventilation had no significant effect on the mortality and the length of ICU stay in ARDS patients, but prone ventilation for > 24 hours increased the incidence of pressure ulcers and the operation of tracheotomy, which still needs to be further verified by a large number of studies due to the small number of included studies.

Association between serum sodium and 28-day mortality in sepsis patients: A secondary data analysis from three large critical illness cohorts.

OBJECTIVE: The present study was designed to explore the association between serum sodium and mortality in patients with sepsis by using a large sample, multicenter MIMIC-IV database. METHODS: We extracted the data of 34 925 sepsis patients from the retrospective cohort mimicIV database. After adjusting the confounders, we explored the independent effects of serum sodium on 28-day mortality. RESULTS: A nonlinear relationship existed between serum sodium and 28-day mortality, of which a negative association was found between serum sodium and 28-day mortality (odds ratio: 0.95, 95% CI: 0.94, 0.96, p = 0.0001) when serum sodium was in 102 mmol/L to 138 mmol/L, but a positive correlation appeared when sodium climbed to the range of 140-179 mmol/L (odds ratio: 1.04, 95% CI: 1.03-1.06, p = 0.0001). CONCLUSIONS: Both lower and higher serum sodium levels are associated with an increased risk of death in sepsis patients.

Association between remote resistance exercises programs delivered by a smartphone application and skeletal muscle mass among elderly patients with type 2 diabetes- a retrospective real-world study.

Objective: We aimed to explore the relationship between remote resistance exercise programs delivered via a smartphone application and skeletal muscle mass among elderly patients with type 2 diabetes, utilizing real-world data. Methods: The resistance exercises were provided through Joymotion®, a web-based telerehabilitation smartphone application (Shanghai Medmotion Medical Management Co., Ltd). The primary outcome was the changes in skeletal muscle index (SMI) before and after the remote resistance exercises programs. The secondary outcomes were changes in skeletal muscle cross-sectional area (SMA), skeletal muscle radiodensity (SMD) and intermuscular adipose tissue (IMAT). Results: A total of 101 elderly patients with type 2 diabetes were analyzed. The participants had an average age of 72.9 ± 6.11 years for males and 74.4 ± 4.39 years for females. The pre- and post-intervention SMI mean (± SE) was 31.64 ± 4.14 vs. 33.25 ± 4.22 cm2/m2 in male, and 22.72 ± 3.24 vs. 24.28 ± 3.60 cm2/m2 in female respectively (all P < 0.001). Similarly, a statistically significant improvement in SMA, IMAT, and SMD for both male and female groups were also observed respectively (P < 0.001). Multiple linear regression models showed potential confounding factors of baseline hemoglobin A1c and duration of diabetes with changes in SMI in male, while hemoglobin A1c and high density lipoprotein cholesterol with changes in SMI in female. Conclusion: Remote resistance exercises programs delivered by a smartphone application were feasible and effective in helping elderly patients with type 2 diabetes to improve their skeletal muscle mass.

Bovine HEXIM1 inhibits bovine immunodeficiency virus replication through regulating BTat-mediated transactivation.

The bovine immunodeficiency virus (BIV) transactivator (BTat) recruits the bovine cyclin T1 (B-cyclin T1) to the LTR to facilitate the transcription of BIV. Here, we demonstrate that bovine hexamethylene bisacetamide (HMBA)-induced protein 1 (BHEXIM1) inhibits BTat-mediated BIV LTR transcription. The results of in vivo and in vitro assays show direct binding of BHEXIM1 to the B-cyclin T1. These results suggest that the repression arises from BHEXIM1-BTat competition for B-cyclin T1, which allows BHEXIM1 to displace BTat from B-cyclin T1. Furthermore, we found that the C-terminal region and the centrally located region of BHEXIM1 are required for BHEXIM1 to associate with B-cyclin T1. Knockdown of BHEXIM1 enhances BIV replication. Taken together, our study provides the first clear evidence that BHEXIM1 is involved in BIV replication through regulating BTat-mediated transactivation.

Alveolar-arterial oxygen gradient nonlinearly impacts the 28-day mortality of patients with sepsis: Secondary data mining based on the MIMIC-IV database.

OBJECTIVE: Lung is often implicated in sepsis, resulting in acute respiratory distress syndrome (ARDS). The alveolar-arterial oxygen gradient [D(A-a)O2 ] reflects lung diffusing capacity, which is usually compromised in ARDS. But whether D(A-a)O2 impacts the prognosis of patients with sepsis remains to be explored. Our study aims to investigate the association between D(A-a)O2 and 28-day mortality in patients with sepsis using a large sample, multicenter Medical Information Mart for Intensive Care (MIMIC)-IV database. METHODS: We extracted a data of 35 010 patients with sepsis from the retrospective cohort MIMIC-IV database, by which the independent effects of D(A-a)O2 on 28-day death risk was investigated, with D(A-a)O2 as being the exposure variable and 28-day fatality being the outcome variable. Binary logistic regression and a two-piecewise linear model were employed to explore the relationship between D(A-a)O2 and the 28-day death risk after confounding factors were optimized including demographic indicators, Charlson comorbidity index (CCI), Sequential Organ Failure Assessment (SOFA) score, drug administration, and vital signs. RESULTS: A total of 18 933 patients were finally included in our analysis. The patients' average age was 66.67 ± 16.01 years, and the mortality at 28 days was 19.23% (3640/18933). Multivariate analysis demonstrated that each 10-mmHg rise of D(A-a)O2 was linked with a 3% increase in the probability of death at 28 days either in the unadjusted model or in adjustment for demographic variables (Odds ratio [OR]: 1.03, 95% CI: 1.02 to 1.03). But, each 10 mmHg increase in D(A-a)O2 was associated with a 3% increase of death (OR: 1.03, 95% CI: 1.023 to 1.033) in the case of adjustment for all covariants. Through smoothed curve fitting and generalized summation models, we found that non-linear relationship existed between D(A-a)O2 and the death at 28-day, which demonstrated that D(A-a)O2 had no any impacts on the prognosis of patients with sepsis when D(A-a)O2 was less than or equal to 300 mmHg, but once D(A-a)O2 exceeded 300 mmHg, however, every 10 mmHg elevation of D(A-a)O2 is accompanied by a 5% increase of the 28-day death (OR: 1.05; 95% CI:1.04 to 1.05, p < 0.0001). CONCLUSION: Our findings suggests that D(A-a)O2 is a valuable indicator for the management of sepsis patient, and it is recommended that D(A-a)O2 be maintained less than 300 mmHg as far as possible during sepsis process.

Morusin and mulberrin extend the lifespans of yeast and C. elegans via suppressing nutrient-sensing pathways.

Compounds with lifespan extension activity are rare, although increasing research efforts have been invested in this field to find ways to extend healthy lifespan. By applying a yeast-based high-throughput assay to identify the chronological lifespan extension activity of mulberry extracts rapidly, we demonstrated that a group of prenylated flavones, particularly morusin and mulberrin, could extend the chronological lifespan of budding yeast via a nutrient-dependent regime by at least partially targeting SCH9. Their antiaging activity could be extended to C. elegans by promoting its longevity, dependent on the full functions of genes akt-1 or akt-2. Moreover, additional benefits were observed from morusin- and mulberrin-treated worms, including increased reproduction without the influence of worm health (pumping rate, pumping decline, and reproduction span). In the human HeLa cell model, morusin and mulberrin inhibited the phosphorylation of p70S6K1, promoted autophagy, and slowed cell senescence. The molecular docking study showed that mulberrin and morusin bind to the same pocket of p70S6K1. Collectively, our findings open up a potential class of prenylated flavones performing their antiaging activity via nutrient-sensing pathways.

Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial.

PURPOSE: We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS: This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS: Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19-/CD22+, one CD19-/CD22-, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients (P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION: CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.[Media: see text].

Comparative analysis of the fusion efficiency elicited by the envelope glycoprotein V1-V5 regions derived from human immunodeficiency virus type 1 transmitted perinatally.

Understanding the properties of viruses preferentially establishing infection during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is critical for the development of effective measures to prevent transmission. A previous study demonstrated that the newly transmitted viruses (in infants) of chronically infected mother-infant pairs (MIPs) were fitter in terms of growth, which was imparted by their envelope (Env) glycoprotein V1-V5 regions, than those in the corresponding chronically infected mothers. In order to investigate whether the higher fitness of transmitted viruses was conferred by their higher entry efficiency directed by the V1-V5 regions during perinatal transmission, the fusogenicity of Env containing V1-V5 regions derived from transmitted and non-tranmsmitted viruses of five chronically infected MIPs and two acutely infected MIPs was analysed using two different cell-cell fusion assays. The results showed that, in one chronically infected MIP, a higher fusion efficiency was induced by the infant Env V1-V5 compared with that of the corresponding mother. Moreover, the V4-V5 regions played an important role in discriminating the transmitted and non-transmitted viruses in this pair. However, neither a consistent pattern nor significant differences in fusogenicity mediated by the V1-V5 regions between maternal and infant variants was observed in the other MIPs. This study suggests that there is no consistent and significant correlation between viral fitness selection and entry efficiency directed by the V1-V5 regions during perinatal transmission. Other factors such as the route and timing of transmission may also be involved.

Clinical Characteristics and the Effect of Timing for Metagenomic Next-Generation Sequencing in Critically Ill Patients with Sepsis.

Background: Metagenomic next-generation sequencing (mNGS) has a good performance for the identification of pathogens in infectious diseases, but few studies on the clinical characteristics of mNGS and the effect of timing for mNGS in critically ill patients with sepsis. Methods: We retrospectively included all patients diagnosed with sepsis after admission to the intensive care unit (ICU) of a university-affiliated hospital between Aug 1, 2019 and Apr 1, 2021. During the study period, pathogens for all enrolled subjects were obtained by mNGS. We analyzed the composition and positive rate of different samples type for mNGS. And then we used the univariable and multivariable logistic regression to explore the risk factors associated with all-cause mortality at 28 days. Results: A total of 87 patients were included and 87 samples were analyzed among these patients. The most common sample for mNGS was bronchoalveolar lavage fluid (BALF), about 84% (73/87). The positive rate of pathogens identification by mNGS was higher than conventional culture (92% vs 36%, p < 0.001). In addition to the pathogens detected by conventional culture, mNGS can detect more viruses and fungi. Based on the mNGS report, clinicians made adjustments to the antibiotic regimen for 72% patients. The multivariate binary logistic regression analysis suggested that age (OR, 1.036; 95% CI, 1.005-1.067; p = 0.021) and the sequential organ failure assessment (SOFA) score on the day of mNGS sampling were independent risk factors of death at 28 days (OR, 1.204; 95% CI, 1.038-1.397; p = 0.014). Conclusion: In critically ill patients with sepsis, the most common sample type for mNGS was BALF, and the positive rate of mNGS is higher than conventional cultures, especially in viruses and fungi. Meanwhile, mNGS can guide clinicians in adjusting antibiotic regimens. Age and the SOFA score on the day of mNGS sampling were independent risk factors for death.