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Sirolimus has been used to treat paediatric kaposiform haemangioendothelioma patients. However, there is considerable pharmacokinetic variability among individuals, and it is difficult to develop an initial dosing regimen. The goal of the present study is to recommend an initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients based on population pharmacokinetics and pharmacogenomics.
This was a retrospective clinical study. A population pharmacokinetics model was established and population characteristics, laboratory test results, drug combinations, and pharmacogenomics were considered as potential covariates. The Monte Carlo method was used to simulate the optimal initial dosage.
The final covariates that affect sirolimus clearance include weight and the
genotype. The initial dosage of sirolimus for individuals with
was 0.20 mg/kg split into two doses for 5 to 60 kg body weight. For individuals with
, the initial dose was 0.23 mg/kg split into two doses for 5 to 30 kg body weight and 0.20 mg/kg split into two doses for 30 to 60 kg body weight.
The recommendation for the initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients was based on population pharmacokinetics and pharmacogenomics. This study may provide practical value for sirolimus clinical use in paediatric kaposiform haemangioendothelioma patients.
The recommendation for the initial sirolimus dose in paediatric kaposiform haemangioendothelioma patients was based on population pharmacokinetics and pharmacogenomics. This study may provide practical value for sirolimus clinical use in paediatric kaposiform haemangioendothelioma patients.At present, autologous stem cell transplantation (ASCT) is considered as an optional consolidation therapy for natural killer/T-cell lymphoma (NKTCL). However, the high-risk patients undergoing ASCT are not clear enough. In this study, 56 patients with advanced staged or relapsed/refractory (R/R) NKTCL undergoing ASCT were reviewed. All patients achieved clinical complete response (CR) before ASCT. The median follow-up time was 36 months (range, 3-192 months). The three-year overall survival (OS) and three-year progression-free survival (PFS) were 70.2% and 56.5%, respectively. The independent prognostic factors for OS included prior testis involvement and pre-ASCT EBV-DNA. Patients without prior testis involvement and negative pre-ASCT EBV-DNA (group A) had better three-year OS (86.3% vs. 47.6%, p less then .001) than the rest patients (group B). In conclusion, our study suggests that testis involvement and elevated EBV-DNA might be strong adverse prognostic factors for NKTCL. Patients without the above risk factors are more likely to benefit from ASCT.Strain improvement of Streptomyces dengpaensis XZHG99T was performed by combined UV mutagenesis and ribosome engineering, as well as fermentation optimization for enhanced angucycline production (rabelomycin and saquayamycin B1). First, four streptomycin-resistant mutants were obtained after screening of UV mutagenesis and ribosome engineering. Then a rpsL mutant (HTT7) with higher productivity of rabelomycin and saquayamycin B1 was selected according to genetic screening and HPLC/LC-MS analyses, whose maximum titers of rabelomycin and saquayamycin B1 were 3.6 ± 0.02 mg/L and 7.5 ± 0.04 mg/L, respectively, about fourfold higher than those produced by XZHG99T. Next, fermentation optimization of HTT7 was successively carried out by single-factor experiments in shake flasks. The titers of rabelomycin and saquayamycin B1 were increased to 11.2 ± 0.04 mg/L and 20.5 ± 0.02 mg/L after optimization of shake flask fermentation conditions, respectively, which was increased about sixfold compared with those produced by XZHG99T. Finally, the titers of rabelomycin and saquayamycin B1 reached 15.7 ± 0.05 mg/L and 39.9 ± 0.05 mg/L after the scaled-up fermentation, which was 7.8-fold and 11.4-fold higher than those produced by XZHG99T, respectively. These data demonstrate that the combined empirical strain-breeding approaches are still an effective and convenient pathway to improve strain production ability.A purposeful sample of 15 mothers of children with severe and profound intellectual disabilities participated in this hermeneutic phenomenological study through interviews and completion of a diary. The aim of the study was to explore mothers' lived experience of 'giving medicines' to children with severe and profound intellectual disabilities. Findings yielded multiple themes, one of which gave insight into the importance of supportive relationships with health professionals. The general practitioner (GP), hospital and pharmacist are key in providing supportive elements to mothers' daily role. Having the support of a helpful GP was key in helping mothers cope on a daily basis for child related queries on illness, getting prescriptions or seeking advice. Accessibility to the hospital and avoiding the emergency department with their child was recommended. The pharmacist was central to the daily activities relating to 'giving medicines' and a good relationship resulted in a happier mother.Possible phenotypic impairments associated with maternal stress during gestation in beef cattle may be explained by epigenetic effects. This study examined the impact of prenatal transportation stress on DNA methylation of lymphocytes of Brahman cows over the first 5 years of life. Methylation analysis through reduced representation bisulphite sequencing was conducted on DNA from lymphocytes from 28 paired samples from 6 prenatally stressed (PNS) and 8 control (Control) females obtained initially when they were 28 days of age and 5 years of age. There were 14,386 CpG (C = cytosine; p = phosphate; G = guanine) sites differentially methylated (P less then 0.01) in 5-yr-old Control cows compared to their lymphocyte DNA at 28 days of age, this number was slightly decreased in 5-yr-old PNS with 13,378 CpG sites. Only 2,749 age-related differentially methylated CpG sites were seen within PNS females. There were 2,637 CpG sites differentially methylated (P less then 0.01) in PNS cows relative to Controls at 5 years of age. There were differentially methylated genes in 5-yr-old cows that contributed similarly to altered gene pathways in both treatment groups. Canonical pathways altered in PNS compared to Control cows at 5 years of age were mostly related to development and growth, nervous system development and function, and immune response. Prenatal stress appeared to alter the epigenome in Brahman cows compared to Control at 5 years of age, which implies a persistent intervention in DNA methylation in lymphocytes, and may confer long-lasting effects on gene expression, and consequently relevant phenotypic changes.
We explored the long-term immunogenicity induced by 60μg and 20μg hepatitis B vaccines among patients receiving methadone maintenance treatment (MMT).
In initial study, a randomized controlled trial was conducted, in which patients receiving MMT were administered 20µg (IM20 group) or 60µg (IM60 group) hepatitis B vaccines at months 0, 1, and 6. this website In this study, the responders at month 7 were followed-up at months 18, 30, and 42 to estimate long-term immunogenicity.
The response rate decreased from 78.0% (39/50) to 31.1% (14/45) in the IM20 group, and from 86.0% (43/50) to 50.0% (20/40) in the IM60 group from month 7 to 42. Vaccine-induced responses in 75% of patients were observed for 14.2months in the IM20 group and for 20.0months in the IM60 group, and differences between these two groups were non-significant (
>0.05).
The three-dose 20µg and 60µg hepatitis B vaccines showed similar rapid hepatitis B surface antibody decreases.
HBV, hepatitis B virus; MMT, methadone maintenance treatment; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; anti-HBs, hepatitis B surface antibody; HR, hazard ratio; CI, confidence interval; IQR, interquartile range; GEE, generalized estimated equation.
The three-dose 20 µg and 60 µg hepatitis B vaccines showed similar rapid hepatitis B surface antibody decreases. Abbreviations HBV, hepatitis B virus; MMT, methadone maintenance treatment; HCC, hepatocellular carcinoma; HBsAg, hepatitis B surface antigen; anti-HBs, hepatitis B surface antibody; HR, hazard ratio; CI, confidence interval; IQR, interquartile range; GEE, generalized estimated equation.
Radioactive iodine (
I) is one of the treatments of hyperthyroidism and differentiated thyroid carcinoma (DTC). Swelling of salivary glands are one of the possible side effects of this treatment, known as radioactive iodine-induced sialadenitis (RAIS). The prevalence of RAIS varies widely and no specific risk ratio has been established.
To determine the incidence of RAIS, analysing the epidemiological data and tumour- and treatment-related factors that may influence the development of the disease.
197 patients who received radioiodine treatment between 2015 and 2017 were studied (76.6% women). The variables studied were age, gender, weight, height, and body mass index; presence of high blood pressure, dyslipidemia, diabetes, and thyroid diseases; cumulative radioiodine dose, presence of sialadenitis, affected salivary gland, and the time of onset.
14 patients developed sialadenitis (78.6% women), all with DTC. The incidence of sialadenitis was 3.4% overall and 6.3% among DTC patients. Furthermore, we found that higher cumulative radioiodine doses confer a greater risk of developing sialadenitis, with a hazard ratio of 1.009 (
= .001). No association was found between the epidemiologic data studied and sialadenitis.
In this series, a dose-dependent relationship was found between radioiodine treatment and sialadenitis.
In this series, a dose-dependent relationship was found between radioiodine treatment and sialadenitis.
Immune checkpoint inhibitors (ICPIs), novel immunotherapy agents employed in the treatment of metastatic melanoma and other solid tumors, are associated with immune-related adverse events, including ocular inflammation. We review the current literature on immune checkpoint inhibitor-associated uveitis (ICIPU).
A comprehensive literature review utilizing MEDLINE/PubMed, Cochrane, and Web of Science databases was conducted. One hundred and twenty-six cases of ICPIU reported in the literature prior to January 31, 2020 were identified and reviewed.
ICPIs were associated with 126 cases of anterior uveitis, intermediate uveitis, posterior uveitis, and panuveitis from 67 reports in the literature. Patients typically developed intraocular inflammation a median of 9 weeks after initiation of ICPI and 83.6% of the patients developed uveitis within 6 months. The vast majority of patients recovered to within one line of baseline vision in response to topical, local, and/or systemic steroid treatment as well as the cessation of medication.
Prompt recognition and steroid treatment of ICPIU are critical to the care of patients receiving ICPIs.
Prompt recognition and steroid treatment of ICPIU are critical to the care of patients receiving ICPIs.
To validate the Russian matrix sentence test (RUMatrix) for the assessment of speech recognition in quiet and in noise in clinical praxis. The effect of hearing impairment, age, and masking-noise level on speech recognition was examined.
All participants underwent pure tone audiometry, a monosyllabic speech test in quiet, and speech recognition measurements with RUMatrix in quiet (SRT
) and in noise (SRT
).
One hundred and forty-two listeners divided into four groups 1. Young normal-hearing listeners, 2. Older normal-hearing listeners, 3. Young hearing-impaired listeners, and 4. Older hearing-impaired listeners.
Significant differences between groups of listeners were found in the SRT
and SRT
. A strong correlation between hearing threshold and SRT
(R
=0.88,
< 0.001) indicates a strong link between speech recognition in quiet and audibility. The pure-tone average explained less variance in SRT
(R
=0.67,
< 0.001), pointing out an additional influence of suprathreshold distortion.
