Κυριακή 27 Νοεμβρίου 2022

Splith mouth randomized control trial comparison of T‐PRF and subepithelial connective tissue graft in the treatment of maxillar multiple gingival recessions

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Abstract

Aim

The aim of this study is to compare the treatment efficacy of the bilateral multiple gingival recession areas with a titanium-platelet-rich-fibrin (T-PRF) and subepithelial connective tissue graft (SCTG) combined with a modified coronal advanced flap (MCAF) and the clinical results.

Method

In the study, 118 maxillary bilateral multiple Miller I recessions were treated. Gingival index, plaque index, probing pocket depth, gingival thickness, recession height, recession width, keratinized gingival width and open root surface area were measured at baseline and at 6 months. Postoperative pain levels Visual Analog Scale, healing status, wound healing index evaluated with. The results of both groups pre and postoperative were compared.

Results

The initial recession height was 2.15 ± 1.0 mm in the T-PRF group; 2.04 ± 0.80 mm in the SCTG group. After 6 months, the mean root closure rate was 61.77%, 75.31% in T-PRF and SCTG group, respectively. Clinical attachment gain was achieved in both groups compared to baseline. When the results were compared, the gains achieved in the SCTG group were statistically significantly higher. İt was determined that patient satisfaction was higher in T-PRF group and wound healing was faster.

Conclusion

Considering the advantages of T-PRF such as providing effective results in the treatment of defects, patient satisfaction and rapid recovery; It can be applied as an alternative to SCTG.

Clinical Significance

T-PRF can be an alternative to SCTG in the treatment of gingival recessions.

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Human Endogenous Retroviruses in Cancer: Oncogenesis mechanisms and Clinical Implications

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Abstract

Human Endogenous Retroviruses (HERVs) are viral sequences integrated into the human genome, resulting from the infection of human germ-line cells by ancient exogenous retroviruses. Despite losing their replication and retrotransposition abilities, HERVs appear to have been co-opted in human physiological functions while their aberrant expression is linked to human disease. The role of HERVs in multiple malignancies has been demonstrated, however, the extent to which HERV activation and expression participate in the development of cancer is not yet fully comprehended. In this review article, we discuss the presumed role of HERVs in carcinogenesis and their promising diagnostic and prognostic implications. Additionally, we explore recent data on the HERVs in cancer therapeutics, either through the manipulation of their expression, to induce anti-tumor innate immunity responses or as cancer immunotherapy targets. Finally, more precise and higher resolution high -throughput sequencing approaches will further elucidate HERV participation in human physiological and pathological processes.

This article is protected by copyright. All rights reserved.

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Survival outcomes for patients with T3N0M0 squamous cell carcinoma of the glottis treated with definitive radiation alone versus chemoradiation

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Abstract

Background

Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis.

Methods

We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation.

Results

A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25–0.37] and 0.48 [0.31–0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%–37.2%] vs. 58.0% [55.8%–60.0%]). In patients <70 with no comorbidities this difference persisted (51.0% [44.5%–57.0%] versus 66.7% [64.0%–69.3%]).

Conclusion

Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.

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Pre‐treatment or post‐treatment with hydroxychloroquine demonstrate neuroprotective effects in cerebral ischemia/reperfusion

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Abstract

Background and Objectives

Stroke is a serious life-threatening medical condition and is one of the principal reasons for death and disabilities worldwide. The aim of the present study was to determine the neuroprotective effects of hydroxychloroquine (HCQ) and the timing of its administration in cerebral ischemia/reperfusion (I/R) in rats.

Methods

A global I/R model was used and HCQ was administered in either pre- or post-treatment doses of 25 and 50 mg/kg. Effects of HCQ on infarct size, histological changes, oxidative stress, as well as learning and memory were evaluated. Phospho-AMPK and SQSTM1/p62 protein levels were also measured to elucidate the possible mechanisms involved.

Results

HCQ in both pre-(at doses of 25 and 50 mg/kg) or post-treatment (at a dose of 50 mg/kg) protocols reduces brain infarct size and histopathological changes and improves learning and memory after cerebral I/R. Pre-treatment with HCQ reduced AMPK activity with no significant effect on SQSTM1/p62 increment. Post-treatment with HCQ increased AMPK activity and SQSTM1/p62 protein levels.

Conclusion

Our results show the neuroprotective effects of HCQ on cerebral I/R through the reduction in infarct size, histopathological changes, as well as improvement in memory and learning functions. Moreover, AMPK and autophagy may play a role in this protective effect.

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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.

This article is protected by copyr ight. All rights reserved.

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

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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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