Predicting central nervous system relapse in primary breast diffuse large B-cell lymphoma using the stage-modified IPI score: A retrospective cohort study.

Objective: The existing Central Nervous System-International Prognostic Index (CNS-IPI) provides insufficient guidance for predicting central nervous system (CNS) relapse in individuals with primary breast diffuse large B-cell lymphoma (DLBCL). This retrospective cohort study sought to examine the potential of the stage-modified IPI in predicting CNS relapse within this specific patient population. Patients and methods: We examined the baseline characteristics of 76 consecutive patients diagnosed with primary breast DLBCL, calculating the stage-modified IPI score for each individual. Utilizing a competing risk regression (CRR) model, we conducted both univariate and multivariate analyses to explore the relationship between potential prognostic factors and the occurrence of CNS relapse. Results: In our cohort, the rates of CNS disease at 2 and 5 years since the diagnosis of primary breast DLBCL are 3.9% and 7.8%, respectively. Among patients experiencing CNS relapse, 80% presented with a parenchymal brain mass. Individuals with a high stage-modified IPI score (1-3 points) had a significantly higher incidence of CNS relapse (p = 0.031), a shorter time from the initial diagnosis of primary breast DLBCL to the first CNS relapse (p = 0.010), as well as relapse at any site (p = 0.012), compared to those with a low score (0 points). Univariate analysis identified stage (Hazard Ratio (HR): 4.098, p = 0.024), stage-modified IPI score (HR: 11.582, p = 0.012), and radiation therapy (HR: 5.784, p = 0.026) as significant risk factors. In multivariate analysis, in addition to radiation therapy (HR: 7.258, p = 0.012), the stage-modified IPI score (1-3 points versus 0 points) emerged as an independent and reliable predictor for CNS relapse (HR: 12.945, p = 0.016). Conclusion: Our study underscores the significance of stage-modified IPI scores in predicting CNS relapse for patients with primary breast DLBCL. Validation of these findings through further research is essential, along with exploring potential prevention and intervention approaches.

Associations of prenatal exposure to per- and polyfluoroalkyl substances and fetal sex hormones in the Guangxi Zhuang Birth Cohort Study: Greater effect of long-chain PFAS.

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.

Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia.

Severe adenoviral pneumonia (SAP) can cause post-infectious bronchiolitis obliterans (PIBO) in children. We aimed to investigate the relevant risk factors for PIBO and develop a predictive nomogram for PIBO in children with SAP. This prospective study analysed the clinical data of hospitalised children with SAP and categorised them into the PIBO and non-PIBO groups. Least absolute shrinkage and selection operator (LASSO) regressions were applied to variables that exhibited significant intergroup differences. Logistic regression was adopted to analyse the risk factors for PIBO. Additionally, a nomogram was constructed, and its effectiveness was assessed using calibration curves, C-index, and decision curve analysis. A total of 148 hospitalised children with SAP were collected in this study. Among them, 112 achieved favourable recovery, whereas 36 developed PIBO. Multivariable regression after variable selection via LASSO revealed that aged < 1 year (OR, 2.38, 95% CI, 0.82-6.77), admission to PICU (OR, 24.40, 95% CI, 7.16-105.00), long duration of fever (OR, 1.16, 95% CI, 1.04-1.31), and bilateral lung infection (OR, 8.78, 95% CI, 1.32-195.00) were major risk factors for PIBO. The nomogram model included the four risk factors: The C-index of the model was 0.85 (95% CI, 0.71-0.99), and the area under the curve was 0.85 (95% CI, 0.78-0.92). The model showed good calibration with the Hosmer-Lemeshow test (χ2 = 8.52, P = 0.38) and was useful in clinical settings with decision curve analysis. CONCLUSION: Age < 1 year, PICU admission, long fever duration, and bilateral lung infection are independent risk factors for PIBO in children with SAP. The nomogram model may aid clinicians in the early diagnosis and intervention of PIBO. WHAT IS KNOWN: • Adenoviruses are the most common pathogens associated with PIBO. • Wheezing, tachypnoea, hypoxemia, and mechanical ventilation are the risk factors for PIBO. WHAT IS NEW: • Age < 1 year, admission to PICU, long duration of fever days, and bilateral lung infection are independent risk factors for PIBO in children with SAP. • A prediction model presented as a nomogram may help clinicians in the early diagnosis and intervention of PIBO.

Effects of prenatal single and mixed bisphenol exposure on bone mineral density in preschool children: A population-based prospective cohort study.

Exposure to bisphenols can affect bone mineral density (BMD) in animals and humans. However, the effects of maternal exposure to bisphenols during pregnancy on bone health in preschool children remain unknown. We aimed to assess the effects of prenatal exposure to single and multiple bisphenols on bone health in preschool children. A total of 230 mother-child pairs were included in this study. Generalized linear regression, restricted cubic spline (RCS), principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) were utilized to assess the relationship between bisphenol levels and bone health in preschool children. Each natural log (Ln) unit increase in tetrabromobisphenol A was related to a 0.007 m/s (95 % CI: -0.015, 0.000) decrease in Ln-transformed speed of sound (SOS) among girls. Decreased BMD Z scores in preschool children were found only in the high bisphenol S exposure group (ß = -0.568; 95 % CI: -1.087, -0.050) in boys. The risk of low BMD (BMDL) was significantly higher in the middle-exposure group (OR = 4.695; 95 % CI: 1.143, 24.381) and high-exposure group of BPS (OR = 6.165, 95 % CI: 1.445, 33.789) compared with the low-exposure group in boys. In girls, the risk of BMDL decreased with increasing bisphenol A concentration (OR = 0.413, 95 % CI: 0.215, 0.721). RCS analysis revealed a U-shaped nonlinear correlation between BPB concentration and BMDL in girls (P-overall = 0.011, P-nonlinear = 0.009). In PCA, a U-shaped dose-response relationship was found between PC2 and the risk of BMDL (P-overall = 0.048, P-nonlinear = 0.032), and a significant association was only noted in girls when stratified by sex. The BKMR model revealed a horizontal S-shaped curve relationship between bisphenol mixtures and BMDL in girls. The results indicated that prenatal exposure to single and mixed bisphenols can affect BMD in preschool children, exerting nonmonotonic and child sex-specific effects.

Association of ultraprocessed foods consumption and cognitive function among children aged 4-7 years: a cross-sectional data analysis.

Background: Sugar-sweetened beverage (SSB) consumption has shown associations with cognitive function in preschool children, but effects of other ultraprocessed foods consumption are rarely discussed in China. This study aimed to investigate the relationship between ultraprocessed food consumption and cognitive function among preschool children in China. Methods: A total of 325 children aged 4-7 years were included from Guangxi Zhuang Birth Cohort in Guangxi Zhuang Autonomous Region, China. Face-to-face interviews with parents using the Food Frequency Questionnaire (FFQ) was conducted to investigate the status of seven ultraprocessed foods consumption (i.e., chocolate, biscuits, candy, fast-food, ice cream, SSBs, and sweet bakery products). The mandarin-language version of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI, Fourth Edition) was applied to assess the cognitive function of children. Multiple linear and logistic regression models were used to assess the associations between ultraprocessed food consumption and the full-scale intelligence quotient (FSIQ) and different domains and risk of cognitive deficit, respectively. Results: We found that frequent consumption of candy (ß = -3.34, 95% CI: -5.62∼-1.06; p = 0.004) and sweet bakery products (ß = -2.77, 95% CI: -5.58∼0.04; p = 0.054) were significant associated with decreased FSIQ scores in the linear regression models. However, only frequent consumption of candy was statistically significantly associated with an increased risk of cognitive deficit (OR = 2.05, 95% CI: 1.11∼3.79; p = 0.023) in the logistic regression models. For the different domains, we found frequent consumption of candy (ß = -3.85, 95% CI: -6.28∼-1.43; p = 0.002) and sweet bakery products (ß = -3.48, 95% CI: -6.47∼-0.49; p = 0.023) was also significantly associated with lower Verbal Comprehension Index (VCI). When combining the seven ultraprocessed foods, we found children who frequently consumed more than two kinds of ultraprocessed foods had a significant decrease of VCI scores (ß = -2.66; 95% CI: -5.12∼-0.19; p = 0.035) too. Conclusion: Our results suggested that frequent consumption of individual (candy and sweet bakery products) and multiple ultraprocessed foods may decrease VCI scores and thereby impact cognitive function in children aged 4-7 years.

Rivaroxaban for the treatment of heparin-induced thrombocytopenia with thrombosis in a patient undergoing artificial hip arthroplasty: A case report.

BACKGROUND: Anticoagulation treatment after lower limb surgery is one of the key methods to avoid thrombosis, and low-molecular-weight heparin is the treatment that is most frequently used in clinical practice. But one uncommon side effect of low-molecular-weight heparin is heparin-induced thrombocytopenia (HIT), which can develop into thrombosis if not caught early or managed incorrectly. CASE SUMMARY: We present a case of a patient who underwent hip arthroplasty and experienced thrombocytopenia due to HIT on the 9th d following the application of low-molecular-weight heparin anticoagulation. We did not diagnose HIT in time and applied 1 unit of platelets to the patient, which led to thrombosis. Luckily, the patient recovered following effective and timely surgery and treatment with rivaroxaban. CONCLUSION: Patients using low-molecular-weight heparin after lower limb surgery need to have their platelet counts regularly checked. If HIT develops, platelet treatment should be given with caution.

Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis.

BACKGROUND: We previously reported results of a pooled analysis of two zanubrutinib studies in relapsed or refractory (R/R) MCL showing better survival outcomes when zanubrutinib is used in second-line versus later-line. Here, we present an updated pooled analysis with a longer follow-up of 35.2 months. METHODS: Data were pooled from two studies-BGB-3111-AU-003 (NCT02343120) and BGB-3111-206 (NCT03206970) of zanubrutinib in R/R MCL. The patients were divided into two groups based on the treatment line of zanubrutinib: the second-line and the later-line group. The inverse propensity score weighting method was used to balance the baseline covariates between the groups. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), PFS, and OS rates, objective response rate (ORR), duration of response (DOR), and safety. RESULTS: Among 112 pooled patients, 41 (36.6%) patients received zanubrutinib as second-line and 71 (63.4%) patients as later-line therapy. After weighting, OS was significantly improved in the second-line versus later-line group (HR, 0.459 [95% CI: 0.215, 0.98]; p = 0.044) with median OS not estimable in both groups. The PFS was similar between the two groups (HR, 0.78 [95% CI: 0.443, 1.373]; p = 0.389) but with numerically longer median PFS in the second-line versus later-line group (27.8 vs. 22.1 months). ORR was numerically higher in the second-line versus later-line (88.6% vs. 85.7%), and DOR was similar between the two groups (25.2 vs. 25.1 months). Zanubrutinib showed a similar safety profile in both groups. CONCLUSION: Zanubrutinib in second-line treatment was associated with significantly improved OS compared with later-line treatment of R/R MCL.

Indirect comparisons of efficacy of zanubrutinib versus orelabrutinib in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed or refractory mantle cell lymphoma.

We conducted two indirect comparisons to estimate the efficacy of zanubrutinib versus orelabrutinib in Chinese patients with relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or R/R mantle cell lymphoma (MCL). An unanchored matching-adjusted indirect comparison (MAIC) was performed in R/R CLL/SLL patients. Individual patient data from zanubrutinib trial (BGB-3111-205) were adjusted to match the aggregated data from the orelabrutinib trial (ICP-CL-00103). A naïve comparison was performed in R/R MCL for the different response assessment methodology and efficacy analysis set between the zanubrutinib (BGB-3111-206) and orelabrutinib (ICP-CL-00102) trials. Efficacy outcomes included ORR and PFS. In R/R CLL/SLL patients, after matching, IRC-assessed ORR was comparable (86.6% vs. 92.5%; risk difference, -5.9% [95% CI: -15.8%-3.8%]); IRC-assessed PFS was similar with a favorable trend in zanubrutinib over orelabrutinib (HR, 0.74 [95% CI: 0.37-1.47]) and the 18-month PFS rate was numerically higher in zanubrutinib (82.9% vs. 78.7%). In R/R MCL patients, naïve comparison showed investigator-assessed ORR was similar (83.7% vs. 87.9%; risk difference, -4.2% [95% CI: -14.8%-6.0%]), and CR rate was significantly higher in zanubrutinib over orelabrutinib (77.9% vs. 42.9%; risk difference, 35.0% [95% CI: 14.5%, 53.7%]). Investigator-assessed PFS was similar with a favorable trend (HR, 0.77 [95% CI: 0.45-1.32]) in zanubrutinib over orelabrutinib and the 12-month PFS rate was numerically higher in zanubrutinib (77.5% vs. 70.8%). MAIC result showed zanubrutinib demonstrated favorable PFS over orelabrutinib for R/R CLL/SLL patients. The naïve comparison showed zanubrutinib had favorable PFS and higher CR rate than orelabrutinib for R/R MCL patients.

Bendamustine in the treatment of patients with indolent non-Hodgkin lymphoma refractory or relapse to rituximab treatment: An open-label, single-agent, multicenter study in China.

BACKGROUND: The optimal treatment strategy for refractory or relapse (R/R) indolent non-Hodgkin lymphoma (iNHL) has not been fully identified. This study aims to investigate the efficacy and tolerance of bendamustine hydrochloride developed in native Chinese corporation in the treatment of patients with R/R iNHL. METHODS: A total of 101 patients from 19 centers were enrolled in this study from July 2016 to February 2019. Bendamustine hydrochloride (120 mg/m2 ) was given on days 1 and 2 of each 21-day treatment cycle for six planned cycles or up to eight cycles if tolerated. Parameters of efficacy and safety were analyzed. RESULTS: The median age of the patients was 53.44 (range, 24.4-74.6) years old. A total of 56 (55.44%) patients completed at least six treatment cycles, and the relative dose intensity was 93.78%. The overall response rate was 72.28%, and the median duration of response was 15.84 months (95% confidence interval [CI], 13.77-27.48 months). Median progression-free survival was 16.52 months (95% CI, 14.72-23.41 months), and the median overall survival was not reached. Grade 3 or 4 hematologic toxicities included neutropenia (77.22%), thrombocytopenia (29.70%), and anemia (15.84%). The most frequent nonhematologic adverse events (any grade) included nausea, vomiting, fatigue, fever, decreased appetite, and weight loss. Seven patients died during the trial, and four cases may be related to the investigational drug. CONCLUSIONS: This study reveals that bendamustine hydrochloride is a feasible treatment option for the indolent B-cell non-Hodgkin lymphoma patient who has not remitted or relapsed after treatment with rituximab. All adverse events were predictable and manageable.

Structuring and validating a prognostic model for low-grade gliomas based on the genes for plasma membrane tension.

Background: Recent studies indicate that cell mechanics are associated with malignancy through its impact on cell migration and adhesion. Gliomas are the most common primary malignant brain tumors. Low-grade gliomas (LGGs) include diffuse LGGs (WHO grade II) and intermediate-grade gliomas (WHO grade III). Few studies have focused on membrane tension in LGGs. Herein, we assessed the prognostic value of plasma membrane tension-related genes (MTRGs) in LGGs. Methods: We selected plasma MTRGs identified in previous studies for analysis. Based on LGG RNA sequencing (RNA-seq) data in The Cancer Genome Atlas, a prognostic signature containing four genes was constructed via log-rank testing, LASSO regression and stepwise multivariate Cox regression and was validated with other datasets. Additionally, functional annotation, pathway enrichment and immune and molecular characteristics of the prognostic model defined subgroups were analyzed. Thereafter, a predictive nomogram that integrated baseline characteristics was constructed to determine the 3, 5, and 10-year overall survival (OS) of patients with LGG. Differentially expressed genes were confirmed via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results: Our MTRG prognostic signature was based on ARFIP2, PICK1, SH3GL2, and SRGAP3 expression levels. The high-risk group was more positively associated with apoptosis and cell adhesion pathways and exhibited a low IDH1 mutation rate, high TP53 mutation rate and a low 1p19q co-deletion rate. The high-risk group also exhibited incremental infiltration of immune cells, more forceful immune activities and high expression of immune checkpoints as well as benefited less from immune therapy compared with the low-risk group. Our prognostic model had better forecasting ability than other scoring systems. We found that the nomogram was a better tool for predicting outcomes for patients with LGG. Finally, qRT-PCR confirmed that SH3GL2 and SRGAP3 expression levels in glioma tissues were significantly lower than those in normal brain tissues. The results of IHC analysis confirmed that SH3GL2 protein expression was higher in patients with longer survival. Conclusion: Our plasma membrane tension-related gene prognostic signature is a prospective tool that can differentiate between prognosis, gene mutation landscape, immune microenvironment, immune infiltration and immunotherapeutic efficacy in LGG.

Clinical Characteristics and Prognostic Factors in Primary Breast Diffuse Large B-Cell Lymphoma.

Background: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of non-Hodgkin lymphoma (NHL) with limited data on the clinical features and prognostic factors. Patients and Methods: A consecutive cohort of patients with PB-DLBCL was retrospectively analyzed in our hospital from February 1997 through July 2018. The primary endpoint is overall survival (OS) contributing to any cause. Results: A total of 76 patients were diagnosed with PB-DLBCL. The median age at diagnosis was 51 years (range: 25-80 years), with female prevalence (98.7%). Forty (52.6%) patients had right-sided breast involvement but no bilateral breast involvement at diagnosis. Overall, disease stages IE and IIE were seen in 55 (72.4%) and 21 (27.6%) patients, respectively. According to the stage-modified International Prognostic Index (IPI), 37 (48.7%) patients were classified in the very good risk group (IPI 0). Of the 72 patients available, the non-germinal center B-cell (non-GCB) subtype of DLBCL was observed in 66 (91.6%) patients. All patients received anthracycline-based chemotherapy, 56 (73.7%) with rituximab, 31 (40.8%) also with additional radiation therapy, and 14 (18.4%) patients received a prophylactic intrathecal injection. Seven (9.2%) patients had refractory disease. With a median follow-up of 6.8 years (range 0.4-25.0 years), 10 (13.2%) patients had a relapse in the central nervous system (CNS) site. The 5-year and 10-year OS of all the patients was 97.2% (95% CI: 99.3-89.5) and 84.8% (95% CI: 70.0-93.5), respectively. The median OS was not reached. The median progression-free survival (PFS) was 10.3 years for patients with PB-DLBCL. The 5-year PFS of all the patients was 76.3% (95% CI: 64.6-84.6). Univariate analysis revealed several prognostic factors, including stage-modified IPI, breast surgery, refractory disease, and CNS relapse. Multivariate analyses produced two independent prognostic factors for patients with PB-DLBCL, including stage-modified IPI score (2-3 versus 0) (hazard ratio: 19.114, 95% CI 1.841 to 198.451, p=0.013) and CNS relapse (hazard ratio: 5.522, 95% CI 1.059 to 28.788, p=0.043). Conclusion: In our cohort, PB-DLBCL clinical features are similar to prior literature reports. Stage-modified IPI score and CNS relapse were associated with overall survival.

Construction and validation of a glioblastoma prognostic model based on immune-related genes.

Background: Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued. Purpose: Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM. Methods: Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandem mass spectrometry and western blotting (WB). Results: Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by protein mass spectrometry and WB. Conclusion: Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research.

Influence of Metabolic Risk Factors on the Risk of Bacterial Infections in Hepatitis B-Related Cirrhosis: A 10-Year Cohort Study.

Aim: The effect of metabolic factors on the risk of bacterial infections (BIs) in patients with hepatitis B virus (HBV)-related cirrhosis has not been demonstrated. This study aimed to explore specific metabolic factors associated with the BIs in these patients. Methods: A population-based cohort of 471 patients with HBV-related cirrhosis was retrospectively enrolled between 2009 and 2019. The primary end point was the incidence of BIs during hospitalization, which were compared according to the metabolism-related indicators, namely, presence of diabetes, level of high-density lipoprotein cholesterol (HDLC) and triglyceride, and body mass index (BMI). The propensity score matching (PSM) was adopted to eliminate baseline discrepancies. Results: Compared with the non-diabetic group, the incidences of BIs were higher in the diabetic group before and after PSM (p = 0.029 and p = 0.027). Similar results were found in the low HDLC group as compared with the normal HDLC group before and after PSM (p < 0.001 and p = 0.025). Further analysis showed that the incidences of BIs in patients with low HDLC alone were lower than patients with both low HDLC and diabetes before and after PSM (p = 0.003 and p = 0.022). Similarly, the incidence of BIs in patients with diabetes alone was lower than those in patients with both low HDLC and diabetes both before and after PSM (p = 0.002 and p = 0.018). However, neither triglyceride nor BMI level was related to BIs in our cohort. Conclusion: In patients with HBV-related cirrhosis, the presence of diabetes and low level of HDLC were risk factors of BIs, showing a synergistic effect.

Epidemiological Characteristics of Parainfluenza Virus Type 3 and the Effects of Meteorological Factors in Hospitalized Children With Lower Respiratory Tract Infection.

Objective: To investigate the relationship between meteorological factors and Human parainfluenza virus type 3 (HPIV-3) infection among hospitalized children. Methods: All hospitalized children with acute lower respiratory tract infections were tested for viral pathogens and enrolled, at the second affiliated hospital of Wenzhou medical university, between 2008 and 2017. Meteorological data were directly obtained from Wenzhou Meteorology Bureau's nine weather stations and expressed as the mean exposure for each 10-day segment (average daily temperatures, average daily relative humidity, rainfall, rainfall days, and wind speed). The correlation between meteorological factors and the incidence of HPIV-3 was analyzed, with an autoregressive integrated moving average model (ARIMA), generalized additive model (GAM), and least absolute shrinkage and selection operator (LASSO). Results: A total of 89,898 respiratory specimens were tested with rapid antigen tests, and HPIV-3 was detected in 3,619 children. HPIV-3 was detected year-round, but peak activities occurred most frequently from March to August. The GAM and LASSO-based model had revealed that HPIV-3 activity correlated positively with temperature and rainfall day, but negatively with wind speed. The ARIMA (1,0,0)(0,1,1) model well-matched the observed data, with a steady R2 reaching 0.708 (Ljung-Box Q = 21.178, P = 0.172). Conclusion: Our study suggests that temperature, rainfall days, and wind speed have significant impacts on the activity of HPIV-3. GAM, ARIMA, and LASSO-based models can well predict the seasonality of HPIV-3 infection among hospitalized children. Further understanding of its mechanism would help facilitate the monitoring and early warning of HPIV-3 infection.

Hexokinase II expression as a prognostic marker in diffuse large B-cell lymphoma: pre- and post-rituximab era.

We aimed to assess HKII expression and its prognostic significance in diffuse large B-cell lymphoma (DLBCL) patients. The HKII protein level was determined by immunohistochemistry in 159 newly diagnosed DLBCL patients, and its relationship with overall response rate, progression-free survival (PFS), and overall survival (OS) was analyzed. HKII was expressed in 95 DLBCL patients (59.7%). HKII-positive patients had poorer outcomes than negative patients for 5-y PFS (68% vs. 84%, p = 0.029) and 5-y OS (78% vs. 94%, p = 0.05). When only patients without no bulky disease, B symptoms, or extranodal involvement who had low IPI scores were considered, those with positive HKII had worse 5y-PFS and 5y-OS (p < 0.05). Multivariate analysis indicated that HKII status was an independent prognostic factor of OS. In subgroup analysis, HKII expression was associated with inferior OS in the CHOP group (p = 0.017). In CHOP group patients without bulky disease or extranodal involvement who had low LDH and low IPI scores (p < 0.05), positive HKII was associated with worse PFS and OS. No differences in PFS and OS, or any independent prognostic factors, were found in the RCHOP group. In DLBCL, HKII is valuable as a prognostic biomarker and may be useful as a tool for assessing disease risk.

Four cycles of R-CHOP followed by two applications of rituximab based on negative interim PET/CT: an analysis of a prospective trial.

BACKGROUND: R-CHOP with or without radiotherapy is the standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). To prevent overtreatment, we assessed whether four cycles of CHOP plus six applications of rituximab was adequate with negative interim PET/CT and the role of consolidation radiotherapy specifically for patients with Waldeyer's ring DLBCL. One hundred and twenty-nine patients with limited-stage DLBCL were enrolled in this open-label, nonrandomized, single-arm, phase 2 clinical trial (NCT01804127). METHODS: All patients were initially treated with 4 cycles of R-CHOP and underwent interim PET/CT. Patients with negative PET/CT (Deauville scores 1-2) received 2 additional cycles of rituximab monotherapy, unless they had any risk factors (primary mediastinal large B-cell lymphoma, extranodal primary or bulky disease). Otherwise, patients received another 2 cycles of R-CHOP. Patients with partial response on interim PET/CT received another 4 cycles of R-CHOP. No radiotherapy was conducted in Waldeyer's ring DLBCL patients with negative PET/CT. The primary endpoint was 3-year progression-free survival (PFS). Overall survival (OS) in this study was compared with those from a historical study (NCT 00854568159). RESULTS: One hundred fifteen interim PET/CT scans (89.1%) were negative after 4 cycles of R-CHOP. An elevated lactate dehydrogenase level was significantly associated with positive interim PET/CT (P < 0.05). A trend of inferior outcome was observed in patients with positive interim PET/CT in terms of 3-year PFS (78.6% vs. 91.9%, P = 0.24) and 3-year OS (85.7% vs. 95.6%, P = 0.16). There were no PFS or OS differences found between patients treated with 4R-CHOP+2R and those treated with 6R-CHOP from a historical control study. Patients with Waldeyer's ring DLBCL and negative interim PET/CT achieved a 3-year PFS of 87.2% and a 3-year OS of 89.7%. CONCLUSIONS: Our results suggested that for interim PET/CT-negative patients without risk factors, the extra 2 cycles of CHOP might be omitted, and radiotherapy might also be omitted in patients with Waldeyer's ring DLBCL without compromising the efficacy. These results need to be confirmed in a randomized study. TRIAL REGISTRATION: clinicaltrials.gov , NCT01804127 . Date of first registration: 05/03/2013.

A Potential Nine-lncRNAs Signature Identification and Nomogram Diagnostic Model Establishment for Papillary Thyroid Cancer.

The purpose of our current study was to establish a long non-coding RNA(lncRNA) signature and assess its prognostic and diagnostic power in papillary thyroid cancer (PTC). LncRNA expression profiles were obtained from the Cancer Genome Atlas (TCGA). The key module and hub lncRNAs related to PTC were determined by weighted gene co-expression network analysis (WGCNA) and LASSO Cox regression analyses, respectively. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis were implemented to analyze the possible biological processes and signaling pathways of hub lncRNAs. Associations between key lncRNA expressions and tumor-infiltrating immune cells were identified using the TIMER website, and proportions of immune cells in high/low risk score groups were compared. Kaplan-Meier Plotter was used to evaluate the prognostic significance of hub genes in PTC. A diagnostic model was conducted with logistic regression analysis, and its diagnostic performance was assessed by calibration/receiver operating characteristic curves and principal component analysis. A nine-lncRNAs signature (SLC12A5-AS1, LINC02028, KIZ-AS1, LINC02019, LINC01877, LINC01444, LINC01176, LINC01290, and LINC00581) was established in PTC, which has significant diagnostic and prognostic power. Functional enrichment analyses elucidated the regulatory mechanism of the nine-lncRNAs signature in the development of PTC. This signature and expressions of nine hub lncRNAs were correlated with the distributions of tumor infiltrating immune cells. A diagnostic nomogram was also established for PTC. By comparing with the published models with less than or equal to nine lncRNAs, our signature showed a preferable performace for prognosis prediction. In conclusion, our present research established an innovative nine-lncRNAs signature and a six-lncRNAs nomogram that might act as a potential indicator for PTC prognosis and diagnosis, which could be conducive to the PTC treatment.

Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study.

Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received ≥1 prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (n = 86) received oral zanubrutinib 160 mg twice daily. The primary endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival (OS) rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970.

Disseminated cryptococcosis with varicella-zoster virus coinfection of idiopathic CD4 + T lymphocytopenia: a case report and literature review.

BACKGROUND: Idiopathic CD4 + T lymphocytopenia (ICL) is a rare immunodeficiency syndrome, unaccompanied by various opportunistic infections. Cryptococcus and varicella-zoster viruse are the most common opportunistic infections. METHOD: We described a case of disseminated cryptococcosis with varicella-zoster virus coinfection in a patient with ICL and reviewed all published reports. A total of 26 cases with cryptococcal meningitis in ICL were enrolled. DISCUSSION: ICL remains poorly understood to clinicians. Patients with cryptococcal meningitis in ICL mostly suffered with headache and fever in a subacute or chronic period, while some patients might have atypical manifestations which makes a difficulty for early diagnosis. Some characteristics of cerebrospinal fluid can help to predict the prognosis of the disease. Cryptococcosis with varicella-zoster virus coinfection is rare but serious. CONCLUSION: We recommed CD4 + T cells should be assessed in patients with unusual or recurrent infections. As the underlying pathophysiology is poorly understood, there is no standard therapy for ICL. Increased awareness of the disease and early prevention for CD4 reduction are needed.

Attitudes of Chinese Patients with Non-alcoholic Fatty Liver Disease Toward Participation in Clinical Trials from a National Multicenter Survey.

BACKGROUND: Many new therapies of non-alcoholic fatty liver disease are being evaluated in clinical trials (CTs), but few of these trials involved sites in China. We evaluated influencing factors of Chinese patients' perspectives in participation in CTs of non-alcoholic fatty liver disease. METHODS: A questionnaire was designed to be completed by patients with non-alcoholic fatty liver disease at eight affiliated hospitals across China. RESULTS: 428 patients were included in this analysis, 63% were male and median age was 37.9 years (30.0-44.0). 54% patients rated "to help others" and 30% "to improve my health status" as the greatest benefit from CTs. The most important concerns were safety (43%) and patients' benefit (26%). Improving liver fibrosis or cirrhosis (53%) and reducing fat in liver (21%) were desired efficacy of new drugs. Possibility of being treated with a placebo for up to 2-6 years played an influential (21%) or very influential (73%) role on participation. Lower education level, lower body mass index, and cirrhosis were positively associated with acceptance of liver biopsies. Anxiety of adverse effects of the new drug and requirement of 2-3 liver biopsies were negatively associated with patients' attitudes toward participating in the trial. CONCLUSION: More than one-third of Chinese patients with NAFLD in this survey are willing to participate in CTs of NASH. For CTs of NASH treatment, potential effects on reversing fibrosis or cirrhosis would positively influence, while adverse effects of the new drug and requirement of multiple liver biopsies would negatively influence participation in our study.