Πέμπτη 20 Οκτωβρίου 2022

Risk factors for high‐dose methotrexate associated toxicities in patients with primary central nervous system lymphoma

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Risk factors for high-dose methotrexate associated toxicities in patients with primary central nervous system lymphoma

In this study, including 54 PCNSL patients with 175 HD-MTX-based chemotherapy courses, the rate of AKI and myelosuppression increased significantly in patients treated with HD-MTX co-administered with VDS. We also found a significant correlation between MTX pharmacokinetics, eGFR before MTX infusion, and toxicity.


Abstract

What is Known and Objective

Methotrexate (MTX) is an antimetabolic antitumor drug with high individual differences and may lead to severe toxicities in a considerable number of patients. This study aimed to explore the factors influencing major adverse events in patients with primary central nervous system lymphoma treated with high-dose MTX (HD-MTX), which could be useful in clinical practice.

Methods

Fifty-four patients who received 175 courses of MTX at 3–8 g/m2 between January 2015 and December 2016 were enrolled in this study. We assessed the association between clinical characteristics, MTX pharmacokinetics, MTX delayed elimination, and adverse events, including hepatotoxicity, acute kidney injury (AKI), and myelosuppression.

Results and Discussion

A total of 124 adverse events occurred after MTX infusion. Using independent sample t-tests, we found that patients with myelosuppression had higher MTX area under the concentration-time curve up to 48 h after infusion (AUC0-48h) (p = 0.001) and MTX peak concentration (Cmax) (p = 0.002). MTX concentrations at 48 and 72 h were higher in patients with AKI than in those without (p = 0.034 and p = 0.041, respectively). Using chi-square tests, we found that AKI was correlated with MTX elimination at either 48 h or 72 h (22.1% vs. 8.2%, p = 0.010). By multivariate logistic regression model, our results showed that baseline level of ALT and WBC had a significant effect on hepatotoxicity (OR = 1.079, 95% CI 1.044–1.116, p = 6.9 × 10−6; OR = 0.808, 95% CI 0.711–0.917, p = 0.001, respectiv ely). Patient's age, eGFR before MTX infusion, and co-administration of vindesine had a significant effect on AKI (OR = 0.960, 95% CI 0.935–0.986, p = 0.003; OR = 1.009, 95% CI 1.001–1.017, p = 0.034; OR = 5.463, 95% CI 1.793–16.646, p = 0.003, respectively). LDH and Co-administration of vindesine had a significant effect on myelosuppression (OR = 0.985, 95% CI 0.972–0.998, p = 0.025; OR = 3.070, 95% CI 1.032–9.133, p = 0.044).

What is New and Conclusion

Our study demonstrated that co-administration of VDS, eGFR before MTX infusion, and the baseline index of laboratory examinations including ALT, WBC, LDH may be useful biomarkers for predicting MTX-induced toxicities.
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Evidence for human infection with avian influenza A(H9N2) virus via environmental transmission inside live poultry market in Xiamen, China

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Abstract

H9N2 avian influenza virus (AIV) has become prevalent in the live poultry market (LPM) worldwide, and environmental transmission mode is an important way for AIVs to infect human beings in the LPM. In order to find evidence for human infection with influenza A(H9N2) virus via environmental contamination, we evaluated one human isolate and three environmental isolates inside LPMs in Xiamen, China. The phylogeny, transmissibility, and pathogenicity of the four isolates were sorted out systematically. As for the H9N2 virus, which evolved alongside the "Avian-Environment-Human" spreading chain in LPMs from the summer of 2019 to the summer of 2020, its overall efficiency of contact and aerosol transmissibility improved, which might contribute to the increasing probability of human infection. This study indicated that environmental exposure might act as an important source of human infection in LPMs.

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Serologic evaluation of vaccine preventable infections and vaccination rates in kidney transplant candidates

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Serologic evaluation of vaccine preventable infections and vaccination rates in kidney transplant candidates

 


Abstract

Introduction

Assessing vaccine serologic status presents opportunities to provide live vaccinations to kidney transplant candidates (KTC). This is especially important given the increased risk of infection while taking lifelong immunosuppression following transplant and the inability to routinely provide live vaccines to patients on immunosuppressive medications. In March 2019, the American Society of Transplantation Infectious Disease Community of Practice (AST-IDCOP) released updated guidelines for vaccination of KTC, which emphasize pretransplant viral serology screening and live vaccine administration prior to transplant.

Primary Endpoint

The primary endpoint of this study was to determine adherence to AST-IDCOP guidelines for live measles, mumps, and rubella (MMR) and VZV vaccination prior to transplant in KTC non-immune by serology.

Methods

This retrospective, descriptive study examined serologic status and rates of live vaccination in 672 patients listed for kidney transplant at our center between July 2014 and July 2019. Secondary endpoints included subgroup analysis of adherence to full AST-IDCOP vaccination recommendations and validation of CDC presumed immunity definitions for measles and VZV.

Results

Seventeen patients (2.7%) were nonimmune by serology for VZV, while 182 (27.1%) were nonimmune by serology to MMR. In a subgroup analysis of the seronegative KTC, none received VZV vaccination, and 6% received MMR vaccination prior to transplant or last follow-up.

Conclusions

Overall, a large portion of KTC had immunity gaps that were not resolved before transplantation. These findings are limited due to the retrospective, single-center nature of this study and should be confirmed with larger, prospective assessments of serologic status and vaccine administration.

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Long-term Traffic-related Air Pollutant Exposure and Amyotrophic Lateral Sclerosis Diagnosis

alexandrossfakianakis shared this article with you from Inoreader
imageBackground: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. Methods: In this population-based case–control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989–2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NOx), carbon monoxide (CO), and fine particles (PM2.5) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NOx, CO). Results: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m3) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = –1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NOx (SD = 20 µg/m3) (–4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m3) (–3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM2.5) (SD = 2.37 µg/m3) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. Conclusions: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis.
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Gestational Hypertensive Disorders and Maternal Breast Cancer Risk

alexandrossfakianakis shared this article with you from Inoreader
imageBackground: Preeclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35–74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported diagnoses of eclampsia, preeclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race–ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean = 10.9 years), 3,198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR = 1.0; 95% CI = 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer.
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Prolonged Dexamethasone Exposure Enhances Zebrafish Lateral-Line Regeneration But Disrupts Mitochondrial Homeostasis and Hair Cell Function

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AbstractThe synthetic glucocorticoid dexamethasone is commonly used to treat inner ear disorders. Previous work in larval zebrafish has shown that dexamethasone treatment enhances hair cell regeneration, yet dexamethasone has also been shown to inhibit regeneration of peripheral nerves after lesion. We therefore used the zebrafish model to determine the impact of dexamethasone treatment on lateral-line hair cells and primary afferents. To explore dexamethasone in the context of regeneration, we used copper sulfate (CuSO4) to induce hair cell loss and retraction of nerve terminals, and then allowed animals to recover in dexamethasone for 48  h. Consistent with previous work, we observed significantly more regenerated hair cells in dexamethasone-treated larvae. Importantly, we found that th...
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