IL-6 and IL-10 Are Associated With Gram-Negative and Gram-Positive Bacteria Infection in Lymphoma.

To investigate the Th1/Th2 cytokine profile in patients with lymphoma during the myelosuppression stage of infection. 52 patients with gram-negative bacterial infection (G- group), 49 patients with gram-positive bacterial infection (G+ group), 51 uninfected patients with lymphoma (uninfected group) and 20 healthy controls (healthy group) were enrolled in this study. We evaluated the quantification of Th1/Th2 cytokines with flow cytometry bead assay (CBA) in the sera to explore a rapid diagnostic method to determine the type of infection and anti-infective effect. The levels of procalcitonin (PCT) were also detected simultaneously. The four groups did not differ with regard to IL-2 and IL-4 (P>0.05). The IFN-γ and TNF-α levels of patients with lymphoma were higher than those of healthy controls (P<0.05). There was significantly upregulated IL-6 and IL-10 expression in the G- group (P<0.001). A similar trend was reflected in the IL-6 of the G+ group, which was significantly increased (P<0.001). However, no significant upregulation was observed for IL-10 in the G+ group. According to the different degrees of increased IL-6 and IL-10 levels, We proposed to use the G- Bacterial Infection Cytokine Profile (G- BICP) and the G+ Bacterial Infection Cytokine Profile (G+ BICP) for the first time to differentiate between Gram-negative and Gram-positive (G-/G+) bacterial infection in adults with lymphoma in the myelosuppression stage after chemotherapy. The IL-6, IL-10 and PCT in the G- group and the IL-6, PCT in the G+ group were significantly decreased at day 4 and day 8 compared with those at day 1. IL-6 and IL-10 are closely associated with the severity and treatment efficacy in adults with lymphomas who develop infections after chemotherapy and can help distinguish between G- and G+ bacterial infections at an early stage.

Value of Contrast-enhanced Ultrasound in Evaluating Synovitis and Predicting Recurrent Joint Bleeding of Hemophilia.

OBJECTIVE: Contrast-enhanced ultrasound (CEUS) is advantageous for evaluating microcirculation, and has been applied to assess arthritis in previous studies. However, CEUS examinations have not been studied for hemophilia arthritis. Hemophilia arthritis is different from other arthritis, because it is induced by spontaneous joint bleeding. Hence, CEUS may have special value in evaluating hemophilia arthritis. The present study assessed the value of CEUS in evaluating synovial hypertrophy and predicting recurrent joint bleeding in severe hemophilia A patients. METHODS: From August 2016 to January 2017, 81 severe hemophilia A patients, who were referred to our hospital for ultrasound joint assessment with conventional ultrasound, were enrolled. Among these 81 patients, 46 patients consented for CEUS examinations on the same day. RESULTS: Compared to color Doppler flow imaging (CDFI), four more joints presented with a blood flow signal under CEUS mode. In addition, the synovial hypertrophy measured by CEUS was thicker than that measured by conventional ultrasound. The ultrasound scores (including the total grey-scale ultrasound score, joint effusion/hemarthrosis, synovial hypertrophy, CDFI semi-quantitative score, and CEUS semi-quantitative score) were significantly higher in the joint bleeding group than in the no joint bleeding group (P<0.05). Furthermore, these ultrasound scores were positively correlated with the joint bleeding frequency, and had the highest correlation with the CEUS score (r=0.620, P<0.05). CONCLUSION: CEUS can more accurately assess the degree of synovial hypertrophy and vascularization, and diagnose synovitis, when compared to conventional ultrasound. In addition, CEUS appears to be essential for evaluating the possibility of recurrent joint bleeding, and providing more reliable evidence for individualized treatment.

Dietary Zinc, Copper, and Selenium Intake and High-Risk Human Papillomavirus Infection among American Women: Data from NHANES 2011-2016.

Studies have shown that the micronutrients, zinc (Zn), copper (Cu), and selenium (Se) are associated with the HPV-associated cervical cancer, yet between dietary Zn/Cu/Se intake and high-risk HPV (hrHPV) infection remain unclear. We obtained publicly available data in the present cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) performed between 2011 and 2016. Dietary Zn, Cu, and Se intakes were assessed from two 24-h diet recalls. A total of 4628 female with the age of 18-59 years were included in this secondary analysis. Comparing the highest with the lowest quartiles of Zn intake, the adjusted odds ratio (aOR) for hrHPV infection was 0.72 (95% CI, 0.54-0.98). The aOR upon comparison of the quartile three with the lowest quartile of Cu intake was 0.67 (95% CI, 0.50-0.90). Whereas no significant association was found between intakes of Se and hrHPV infection in multivariate analysis. Moreover, compared with those below the Recommended Dietary Allowance (RDA), hrHPV infection risk was significantly decreased among women who met the RDA for Cu (aOR: 0.74; 95% CI = 0.60-0.92), but not for Zn and Se. In conclusion, high dietary Zn and moderate copper intakes were independently and negatively associated with hrHPV infection in addition to Se.

The successful treatment of Enterocytozoon bieneusi Microsporidiosis with nitazoxanide in a patient with B-ALL: A Case Report.

Introduction: Enterocytozoon bieneusi (E. bieneusi) Microsporidia can cause opportunistic infections in immunocompromised patients and is also an emerging disease in these individuals. Its clinical manifestations are chronic diarrhea and severe wasting syndrome, these can be extremely debilitating and carry a significant risk of death for immunocompromised patients. Often, microsporidia cannot be confirmed immediately by routine examination and culture. Effective and available treatment options are limited for infections caused by E. bieneusi in humans. Such cases are very rare in Chinese Mainland. Case presentation: A 47-year-old male had recurrent, profuse watery diarrhea and abdominal discomfort for more than 7 months, with a fever for 5 days. Two years earlier, he received treatment with a modified BFM-90 protocol for acute B cell lymphoblastic leukemia and is currently in the final stages of maintenance therapy with oral methotrexate and mercaptopurine. The leukemia was assessed as still in remission two months ago. PET/CT showed massive peritoneal fluid accumulation and a high uptake area in the diffused peritoneum (SUVmax 12.57), suggesting tumor invasion or microbial infections. However, broad-spectrum antibacterial therapies were ineffective. Metagenomic sequencing of plasma and peritoneal fluid showed no suggestion of the existence of a tumor but instead showed a high sequence number of DNA and RNA of the Microsporidia. His albendazole treatment failed and subsequent treatment with nitazoxanide successfully resolved the infection. Conclusion: This case shows that we should consider the possibility of atypical pathogen infection in patients with hematologic malignancy who repeatedly develop unexplained diarrhea with wasting. mNGS can help rule out malignant neoplasms and diagnose infections. Our results suggest that nitazoxanide effectively treats E. bieneusi microsporidia infections.

A Real-World Observation of Eltrombopag and Recombinant Human Thrombopoietin (rhTPO) in Lymphoma Patients With Chemotherapy Induced Thrombocytopenia.

This real-world, observational study aimed to assess and compare the clinical efficacy and safety of eltrombopag with recombinant human thrombopoietin (rhTPO) in the treatment of chemotherapy induced thrombocytopenia (CIT) in patients with lymphoma. One hundred and fifty-three patients who experienced grade 3 or 4 thrombocytopenia after chemotherapy for lymphoma were enrolled, 51 of which were treated with eltrombopag, 50 with rhTPO, and 52 patients with no drug treatment were served as the control group. The lowest platelet level and mean platelet counts at Day 5, Day 7, and Day 10 were significantly higher in both the eltrombopag group (P=.041,.003,.000,.000) and rhTPO group (P=.005,.005,.000,.000) than the control, but there was no difference between treatment with eltrombopag and rhTPO. Similarly, days required for the recovery of platelet counts to ≥50×109/L and ≥75×109/L were not different between the two treatment groups but significantly higher than the control group (P <.05). Rates of bleeding and platelet transfusion were all significantly reduced in patients treated with eltrombopag (P=.031,.032) or rhTPO (P=.017,.009) when compared to the control. Treatment-related adverse events (AEs) were reported in 7 (13.7%) and 6 (12.0%) patients in the eltrombopag and rhTPO groups, respectively, all being mild and transient in nature. In conclusion, both eltrombopag and rhTPO were effective and safe in the treatment of thrombocytopenia after chemotherapy for lymphoma.

Ruxolitinib combined with doxorubicin, etoposide, and dexamethasone for the treatment of the lymphoma-associated hemophagocytic syndrome.

PURPOSE: Case reports suggest that ruxolitinib-containing treatment could increase the clinical response rate of patients with hemophagocytic syndrome (HPS). This study aimed to explore the effect of ruxolitinib-containing treatment for patients with lymphoma-associated hemophagocytic syndrome (LAHS). METHODS: This was a retrospective study of patients with LAHS hospitalized at the First Affiliated Hospital of Guangdong Pharmaceutical University between October 2017 and September 2019. Patients were treated with HLH-94 (etoposide and dexamethasone) or R-DED regimen (ruxolitinib, doxorubicin, etoposide, and dexamethasone). The clinical characteristics, treatment responses, and overall survival (OS) were compared. The patients were divided into the HLH-94 group (n = 34) and the R-DED group (n = 36). RESULTS: Compared with HLH-94, R-DED might effectively improve the clinical manifestations, including fever and splenomegaly in patients with LAHS, and control the systemic cytokine storm. The response rate at 2 weeks was 54.8% in the HLH-94 group, which was lower than in the R-DED group (83.3%) (p = 0.011). The OS was significantly prolonged in the R-DED group compared with the HLH-94 group (median, 5 vs. 1.5 months, p = 0.003). The multivariable analysis showed that lower IL-10 levels [hazard ratio (HR)] = 1.000, [95% confidence interval (CI)] 1.000-1.000, p = 0.012), R-DED regimen (HR = 0.196, 95% CI 0.084-0.457, p < 0.001), and non-NK/T-cell lymphoma (HR = 0.254, 95% CI 0.102-0.628, p = 0.003) were associated with better OS. The prognosis of patients with LAHS was generally poor. CONCLUSION: Ruxolitinib can be combined with chemotherapy in HPS. It is feasible, with no early signals of increased toxicity.

[Breakthrough bleeding in adult patients with severe hemophilia A receiving low- and intermediate-dose FVIII for tertiary prophylaxis: characteristics and influencing factors].

OBJECTIVE: To investigate the characteristics of breakthrough bleeding in adult patients with severe hemophilia A (SHA) receiving low- and intermediate-dose FVIII for tertiary prophylaxis and explore the factors affecting the outcomes of the treatment. METHODS: Forty-nine patients (mean age 31.53∓7.33 years) with SHA receiving tertiary prophylaxis FVIII treatment were divided into low-dose group (n=15) and intermediate-dose group (n=34). The data including clinical bleeding phenotype (Pre?AJBR), 72 h FVIII trough activity, and Functional Independence Score in Hemophilia (FISH) were recorded in all the patients, and Hemophilia Steward APP was used to record the bleeding episode and the treatment data. All the patients were followed up for at least 6 months. RESULTS: In the low-dose and intermediate-dose groups, the number of joint bleeding (AJBR) episodes were 18.79∓13.03 and 9.28∓7.02 per year (P=0.016), and the proportions of spontaneous bleeding were 75.0% and 47.7%, respectively. The proportions of patients with target joint were 80% and 44%, target joint bleeding occurred in 59% and 41%, and cataract bleeding after 0-12 h of prophylactic injection occurred in 4.86% and 5.18% of the patients with a median breakthrough bleeding time of 40.08 h and 46.08 h (P=0.008), respectively. The proportions of patients with 72 h FVIII trough activity <1% were 44.4% and 34.8% in the two groups, respectively. AJBR was negatively correlated with the preventive dose consumed (r=-0.57, P=0.000, n=49) and FISH, but positively correlated with Pre-AJBR in the two groups (P<0.05). CONCLUSION: Tertiary prophylaxis with low- and intermediate-dose FVIII is not sufficient to achieve the goal of preventing progression of joint disease in Chinese adult patients with SHA. Although the prophylactic dose is the most important factor to affect the treatment efficacy, other non-factor approaches may also help to improve the efficacy of the treatment.