Πέμπτη 24 Νοεμβρίου 2022

Clinical and laboratory features and factors predicting disease severity in pediatric patients with hemorrhagic fever with renal syndrome caused by Hantaan virus

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Abstract

The clinical features and factors associated with disease severity in children with hemorrhagic fever with renal syndrome (HFRS) have not been well characterized. This study analyzed the clinical and laboratory factors associated with disease severity in children with HFRS caused by Hantaan virus. Data in pediatric patients with HFRS were retrospectively collected from Xi'an Children's Hospital over a 9-year period. Independent factors associated with disease severity were identified. Nomogram predicting disease severity was constructed based on variables filtered by feature selection. In total, 206 children with HFRS were studied. Fever, digestive tract symptoms, headache, backache, bleeding and renal injury signs were the common symptoms. Elevated white blood cell, reduced platelet, hematuria, proteinuria, coagulation abnormalities, increased blood urea nitrogen (BUN) and procalcitonin (PCT), decreased estimated glomerular filtration rate and low serum Na< sup>+, Cl- and Ca2+ were the common laboratory findings. In the 206 patients, 21 patients had critical type disease and 4 patients (1.9%) died. Hydrothorax, hypotension and cerebral edema/cerebral herniation at hospital admission were independent clinical characteristics, and neutrophil %, prothrombin activity, PCT, BUN and Ca2+ at hospital admission were independent laboratory factors associated with critical disease. Feature selection identified BUN, PCT and prothrombin time as independent factors related to critical disease. A nomogram integrating BUN and PCT at admission was constructed and calibration showed high accuracy for the probability prediction of critical disease. In conclusion, this study characterized the clinical and laboratory features and constructed a nomogram predicting disease severity in pediatric HFRS, providing references for disease severity evaluation in managing children HFRS.

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Optimal exposure to docetaxel in adjuvant chemotherapy for early‐stage breast cancer

alexandrossfakianakis shared this article with you from Inoreader
Optimal exposure to docetaxel in adjuvant chemotherapy for early-stage breast cancer

Among the 70 participants, 47 (67.1%) developed severe neutropenia. The PopPK analysis showed that the typical drug clearance (CL) rate was 37.4 L/h. Age was a significant covariate of CL rate, and aspartate aminotransferase and albumin levels were covariables of the volume of distribution. The AUC estimated using the maximum a posteriori Bayesian method can predict the toxicity of docetaxel in patients with breast cancer. Docetaxel AUC >3.0 mg h/L, platinum and baseline haemoglobin level are risk factors for docetaxel-induced grade 3/4 neutropenia. The AUC of first cycle may not predict the occurrence rates of grade 3/4 neutropenia in later cycles.


Abstract

What Is Known and Objective

Drug-induced neutropenia is the main reason for the dose limitation of docetaxel in patients with breast cancer. The area under the drug concentration-time curve (AUC) of docetaxel is associated with neutropenia. However, the optimal exposure to docetaxel for receiving postoperative adjuvant chemotherapy remains unclear. Therefore, we aimed to evaluate the relationship between the docetaxel AUC and neutropenia, identify potential influencing factors, and explore the best monitoring target for docetaxel when treating patients with early-stage breast cancer using a population pharmacokinetic (PopPK) model.

Methods

Docetaxel plasma concentration, demographics, clinical data, and related laboratory data were collected. PopPK analyses were performed using a nonlinear mixed-effect modelling program. The docetaxel AUC was determined using the maximum a posteriori Bayesian (MAPB) method. The docetaxel exposure-toxicity threshold measured from the AUC for neutropenia was determined using the receiver operating characteristic (ROC) curve. The correlation between docetaxel exposure and neutropenia was analysed using multivariable logistic regression.

Results

Among the 70 participants, 47 (67.1%) developed severe neutropenia. The PopPK analysis showed that the typical drug clearance (CL) rate was 37.4 L/h. Age was a significant covariate of CL rate, and aspartate aminotransferase and albumin levels were covariables of the volume of distribution. The multivariable regression analysis showed that AUC >3.0 mg.h/L (odds ratio [OR], 5.940; 95% confidence interval [CI], 1.693–20.843; P = 0.005), platinum use (OR, 0.156; 95% CI, 0.043–0.562; P = 0.005) and baseline haemoglobin level (OR, 0.938; 95% CI, 0.887–0.993; P = 0.027) were significant factors influencing the occurrence of grade 3/4 neutropenia. The AUC of first cycle may not predict the occurrence rates of grade 3/4 neutropenia in later cycles.

What Is New and Conclusion

We developed a docetaxel PopPK model for patients with early-stage breast cancer. Age and AST and ALB levels were significant covariates. AUC estimated using the MAPB method can predict the toxicity of docetaxel in patients with breast cancer. Docetaxel AUC >3.0 mg.h/L, absence of platinum use and low baseline haemoglobin level were risk factors for docetaxel-induced grade 3/4 neutropenia.

Study Registration

Chinese Clinical Trial Center Registry (ChiCTR2200056460).

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Impact of maximal extent of resection on postoperative deficits, patient functioning and survival within clinically important glioblastoma subgroups

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Abstract
Background
The impact of extent of resection (EOR), residual tumor volume (RTV), and gross-total resection (GTR) in glioblastoma subgroups is currently unknown. This study aimed to analyze their impact in patient subgroups in relation to neurological and functional outcomes.
Methods
Patients with tumor resection for eloquent glioblastoma between 2010 and 2020 at four tertiary centers were recruited from a cohort of 3919 patients.
Results
One thousand and forty-seven (1047) patients were included. Higher EOR and lower RTV were significantly associated with improved OS and PFS across all subgroups, but RTV was a stronger prognostic factor. GTR based on RTV improved median OS in the overall cohort (19.0 months, p<0.0001), and in the subgroups with IDH wildtype tumors (18.5 months, p=0.00055), MGMT methylated tumors (35.0 months, p<0.0001), aged <70 (20.0 months, p<0.0001 ), NIHSS 0-1 (19.0 months, p=0.0038), KPS 90-100 (19.5 months, p=0.0012), and KPS ≤ 80 (17.0 months, p=0.036). GTR was significantly associated with improved OS in the overall cohort (HR 0.58, p=0.0070) and improved PFS in the NIHSS 0-1 subgroup (HR 0.47, p=0.012). GTR combined with preservation of neurological function (OFO 1 grade) yielded the longest survival times (median OS 22.0 months, p <0.0001), which was significantly more frequently achieved in the awake mapping group (50.0%) than in the asleep group (21.8%) (p<0.0001).
Conclusions
Maximum resection was especially beneficial in the subgroups aged <70, NIHSS 0-1, and KPS 90-100 without increasing the risk of postoperative NIHSS or KPS worsening. These findings may assist surgical decision making in individual glioblastoma patients.
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Predictive effect of pretreatment nutritional risk and GLIM‐defined malnutrition on the nutrition impact symptom clusters in patients with head and neck cancer undergoing radiotherapy

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Background

Evidence supporting predictive effects of pretreatment nutritional risk and nutritional status on nutrition impact symptom (NIS) clusters during radiotherapy in patients with head and neck cancer (HNC) is insufficient.

Methods

At baseline (T1), we collected severity and interference of NIS (Head and Neck Patient Symptom Checklist), nutritional risk, and nutritional status. During (T2) and at the end of radiotherapy (T3), we re-evaluated NIS. Symptom clusters were identified by exploratory factor analysis using mean scores of NIS severity at T2 and T3. Predictive effects were explored by generalized estimating equations.

Results

Five hundred thirty-seven patients were recruited and 334 of them completed. Four clusters were identified; the oropharyngeal symptom cluster was the most severe and had the greatest interference with diet. Patients with pretreatment nutritional risk or malnutrition experienced more severe oropharyngeal symptom cluster.

Conclusions

Pretreatment nutritional risk or malnutrition could predict the oropharyngeal symptom cluster in patients with HNC undergoing radiotherapy.

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