Αρχειοθήκη ιστολογίου

Κυριακή 27 Νοεμβρίου 2022

Three‐dimensional evaluation of sleep bruxism‐related splint wear using a dental laboratory scanner: a preliminary clinical study

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Abstract

Background:

The wear depth on the occlusal splint (OS) is reportedly associated with the sleep bruxism (SB) level, as evaluated using portable polysomnography (PSG) recordings. However, the OS is deformed owing to SB forces, possibly preventing the accurate quantification of the wear facets.

Objectives:

To introduce a newly developed system to quantify the wear facets on the OS using a dental laboratory scanner (D810) and investigate the association between the wear facets, as evaluated with this system, and the SB level.

Methods:

Ten healthy individuals who were diagnosed with SB based on portable PSG recordings participated in this study. They were asked to wear the OS for 2 months. The first day after a 2-week adaptation period was defined as the reference day, and sequential scanning of the OS surface was performed on days 15, 30, and 45. Changes in the OS surface from the reference day allowed dimensional evaluation of the wear facets in terms of the maximum wear depth, wear area, and wear volume. Multiple regression analyses were conducted to test whether each of these variables could be predicted by any of the SB-related variables.

Results:

The total duration of SB episodes per hour of sleep and the maximum muscle activity were significantly associated with the wear area, as measured with our system (adjusted R-squared was 0.78, p < 0.01).

Conclusion:

Our system allows dimensional analysis of the wear facets on the OS surface in association with the SB level.

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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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Prognostic significance of circulating Epstein‐Barr virus DNA in pulmonary lymphoepithelioma‐like carcinoma: a meta‐analysis and validation study

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Abstract

Background

In small-scale studies, circulating Epstein-Barr virus (EBV) DNA levels have prognostic value in patients with pulmonary lymphoepithelioma-like carcinoma (LELC). Therefore, we performed a comprehensive meta-analysis to evaluate the prognostic significance of circulating EBV DNA levels in patients with pulmonary LELC.

Methods

Studies that discussed the prognostic significance of circulating EBV DNA detection in pulmonary LELC were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Pooled hazard ratio (HR), 95% confidence intervals (CIs), and P-value were calculated to estimate the prognostic significance of EBV DNA levels. Additionally, we conducted a further observation using an independent cohort.

Results

The pooled HR and 95% CI of pre-treatment EBV DNA levels for OS and PFS were 3.63 (95% CI: 2.90–4.55) and 2.88 (95% CI: 1.90–4.38), respectively. The pooled HR and 95% CI for post-treatment EBV DNA levels for OS and PFS were 3.77 (95% CI: 2.96–4.80) and 3.52 (95% CI: 1.91–6.51, P<0.001), respectively. The independent cohort showed similar results that patients with high pre-treatment EBV DNA or positive post-treatment EBV DNA had significantly inferior PFS.

Conclusion

Circulating EBV DNA levels provide prognostic values of survival and treatment response in pulmonary LELC patients.

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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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Rate of atypical nodal metastases in surgically treated HPV‐associated oropharyngeal squamous cell carcinoma

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Abstract

Background

Understanding of nodal metastasis in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC) is warranted.

Methods

Patients with HPV+ OPSCC who underwent neck dissection (ND) between 2016 and 2021 were reviewed. Pathology reports were reviewed for lymph node (LN) metastases. Noncontiguous metastases were defined as pathologic evidence of level II disease with another involved LN in a noncontiguous neck level. Skip metastases were defined as pathologic lymph node(s) in the neck without disease in level II.

Results

One hundred and thirty-one patients underwent levels II–IV ND with a mean (SD) LN yield of 33.3 (±13.5). The rate of atypical metastases in both the therapeutic and elective ND cohort was 5%. The noncontiguous and skip metastases were in level IV (n = 2) and level III (n = 4), respectively.

Conclusions

Skip and noncontiguous metastases were rare in patients with HPV+ OPSCC undergoing surgical treatment. Surgeons may consider a selective ND omitting Level IV in select patients with HPV+ OPSCC undergoing surgery.

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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

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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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