Τρίτη 28 Ιουνίου 2022

An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer

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imageObjectives: This study explored the feasibility of cetuximab with chemoradiation in women with cervical carcinoma and evaluated fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to assess early response to cetuximab (NCT00292955). Patients and Methods: Eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVB invasive carcinoma of the uterine cervix were treated on 1 of 3 dose levels (DL). DL1 consisted of neoadjuvant cetuximab, then concurrent radiotherapy with cetuximab 250 mg/m2/cisplatin 40 mg/m2, followed by weekly cetuximab. DL2 consisted of radiotherapy with cetuximab 200 mg/m2 and cisplatin 30 mg/m2. DL3 consisted of radiotherapy with cetuximab 250 mg/m2 and cisplatin 30 mg/m2. Patients underwent 18F-FDG-PET/CT before treatment, after neoadjuvant cetuximab, and at the end of treatment. Results: Of the 21 patients enrolled, 9, 3, and 9 were treated in DL1, DL2, and DL3, respectively. DL1 required dose reductions due to gastrointestinal toxicities. DL2 and 3 were tolerated with 1 dose-limiting toxicity (grade 4 renal failure) at DL3. Following 3 weekly treatments of neoadjuvant cetuximab in DL1, 7 patients had maximum standardized uptake value changes on 18F-FDG-PET/CT consistent with response to cetuximab. Of the 12 patients with locally advanced disease, eleven evaluable patients had no evidence of disease on 18F-FDG-PET/CT at treatment end. Five-year progression-free survival and overall survival rates for all patients were 57.5% and 58.5%, respectively. Conclusions: Cetuximab with cisplatin 30 mg/m2 and radiotherapy was tolerated. 18F-FDG-PET/CT demonstrated early evidence of response to neoadjuvant cetuximab. With advances in precision oncology and the recent approval of pembrolizumab in metastatic cervical cancer, dual-target inhibition with an epidermal growth factor receptor inhibitor may be a promising treatment in the future.
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Irrigant flow in the root canal during ultrasonic activation: a numerical fluid‐structure interaction model and its validation

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Abstract

Aim

a. To develop a three-dimensional numerical model combining the oscillation of a tapered ultrasonic file and the induced irrigant flow along with their two-way interaction in the confinement of a root canal. b. To validate this model through comparison with experiments and theoretical (analytical) solutions of the flow.

Methodology

Two partial numerical models, one for the oscillation of the ultrasonic file and another one for the irrigant flow inside the root canal around the file, were created and coupled in order to take into account the two-way coupled fluid-structure interaction. Simulations were carried out for ultrasonic K-files and for smooth wires driven at four different amplitudes in air or inside an irrigant-filled straight root canal. The oscillation pattern of the K-files was determined experimentally by Scanning Laser Vibrometry and the flow pattern inside an artificial root canal was analyzed using high-speed imaging together with Particle Image Velocimetry. Analytical solutions were obtained from an earlier study. Numerical, experimental and analytical results were compared to assess the validity of the model.

Results

Comparison of the oscillation amplitude and node location of the ultrasonic files and of the irrigant flow field showed a close agreement between the simulations, the experiments, and the theoretical solutions.

Conclusions

The model is able to predict reliably the file oscillation and irrigant flow inside root canals during ultrasonic activation under similar conditions.

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Children's food choices are highly dependent on patterns of parenting practices and food availability at home in families at high risk for type 2 diabetes in Europe. Cross‐sectional results from the Feel4Diabetes‐study.

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ABSTRACT

Introduction

Food parenting practices, behaviours, and food availability at home are associated with children's food choices; however, these associations have been mainly studied for each parenting practice separately and focused mostly on healthy populations.

Aim

To identify patterns of parenting practices (including data regarding food availability at home, food and physical activity related behaviours and rewards) and to investigate their cross-sectional associations with children's food choices in families at high risk for type 2 diabetes (T2D).

Materials-Methods

Data of parents and children, (N=2278), from the Feel4Diabetes-study conducted in 6 European countries, were collected using validated questionnaires. The data analysed included children's food choices, food availability at home and food and physical activity related parenting practices. Four patterns of parenting practices were identified using principal component analysis and asso ciations between those components and children's food choices were assessed using adjusted, individual linear regressions.

Results

Parenting patterns focusing on unhealthy habits, such as allowing unhealthy snacks and unlimited screen time, providing higher availability of unhealthy foods at home, rewarding with snacks and screen time) were positively associated with children's unhealthy food choices (consumption of savoury/sweet snacks, fizzy drinks etc.). The parenting pattern providing fruit/vegetables availability at home, consuming fruit and being physically active with the child was positively associated with healthier children's food choices (consumption of fruit, vegetables, whole grain cereals etc.).

Conclusion

Public health initiatives should focus on families at high-risk for T2D, assisting them adopt appropriate parenting practices and behaviours to promote healthier food choices for children.

This article is protected by copyright. All rights reserved.

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Κυριακή 26 Ιουνίου 2022

Asphericity of tumor [123I]mIBG uptake as a prognostic factor in high‐risk neuroblastoma

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Abstract

Background

In recent years, many research groups have attempted to identify a subgroup of "ultra-high risk" patients within the high-risk neuroblastoma (NB) category. The aim of our study was to evaluate the prognostic significance of parameters derived from pretherapeutic 123I-meta-iodobenzylguanidine ([123I]mIBG) integrated single photon emission computed tomography and computed tomography in high-risk patients with NB.

Methods

The established parameters metabolic tumor volume (MTV), maximal standardized uptake value (SUVmax) and the novel parameter tumor asphericity as well as clinical (age, stage) and genetic factors (1p/11q deletions and MYCN amplification) were analyzed in this single-center retrospective study of high-risk patients with newly diagnosed NB. Univariate/multivariable Cox regression and propensity score matching were performed for clinical and radiological parameters.

Results

Twenty-eight high-risk patients with NB were included (14 males, median age 28.8 (11.3–41.0), range 3–74 months). Multivariable analysis of "full" cohort identified high asphericity (≥65%, adjusted hazard ratio [HR] 5.32, 95% confidence interval [CI]: 1.18–24.07, = .03) and MTV (≥50 ml, adjusted HR 4.31, 95% CI: 1.18–15.80, p = .027) as the only factors associated with worse event-free survival. In matched cohort, tumor asphericity was a significant predictor of relapse/progression (HR 3.83, 95% CI: 1.03–14.26, p = .046).

Conclusion

In this exploratory study, imaging parameters related to tumor metabolic activity, tumor asphericity and MTV, provided prognostic value for event-free survival in high-risk NB patients. Asphericity ≥65% and MTV ≥50 ml may serve as additional prognostic factors to those already used.

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Can the Remote Use of a Peak Flow Meter Predict Severity of Subglottic Stenosis and Surgical Timing?

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Objective

We aimed to assess the relationship between patient-performed and patient-reported peak flow meter (PFM) measurements with pulmonary function testing (PFT) and Dyspnea Index (DI) scores as a tool for monitoring Subglottic stenosis (SGS) disease progression remotely.

Methods

Thirty-five SGS patients were prospectively enrolled. Patients were given PFMs to report serial measurements from home. DI scores and PFT were recorded at serial clinic visits. Data were analyzed to determine the correlation between PFM measurements and PFT data. Pre-operative and post-operative PFM measurements, PFT, and DI scores were analyzed for patients who underwent operative intervention. Receiver operating characteristic (ROC) curves were created for PFM measurements, PFT data, and DI scores to predict the likelihood of surgery.

Results

PFM measurements had a "strong" correlation with the peak expiratory flow rate (PEFR), r = 0.78. Means of PEFR, PIFR, EDI, PFM measurements, and DI scores all significantly improved after the operative intervention (p ≤ 0.05). The area under the curve for ROC curves for DI scores, PFM measurements, and EDI were highest in our cohort with values of 0.896, 0.823, and 0.806, respectively.

Conclusion

In our SGS cohort, PFM measurements correlate strongly with PEFR measurements. PFM measurements can adequately demonstrate disease progression and predict the need for surgery in this patient population. Together, DI scores and PFM measurements may be a useful tool to remotely follow patients with SGS and inform timing of in-person assessments.

Level of Evidence

2 Laryngoscope, 2022

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When Effects Cannot be Estimated: Redefining Estimands to Understand the Effects of Naloxone Access Laws

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Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world thr eats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effects of Naloxone Access Laws on opioid overdose rates. Violations of the positivity assumption (also called the common support condition) challenge health policy research and can result in significant bias, large variance, and invalid inference. We define positivity in the single- and multiple-timepoint (i.e., longitudinal) health policy evaluation setting, and discuss real-world threats to positivity. We show empirical evidence of the practical positivity violations that can result when attempting to estimate the effects of health policies (in this case, Naloxone Access Laws). In such scenarios, an alternative is to estimate the effect of a shift in law enactment (e.g., the effect if enactment had been delayed by some number of years). Such an effect corresponds to what is called a modified treatment policy, and dramatically weakens the required positivity assumption, thereby offering a means to estimate policy effects even in scenarios with serious positivity problems. We apply the approach to define and estimate the longitudinal effec ts of Naloxone Access Laws on opioid overdose rates. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Effect of body weight on bleeding events of aspirin in ischemic stroke or transient ischemic attack patients

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Effect of body weight on bleeding events of aspirin in ischemic stroke or transient ischemic attack patients

Bodyweight and combination with SSRIs are related to bleeding adverse reaction of aspirin. Patients weighted less than 60 kg will be at a higher risk of adverse bleeding events.


Abstract

What is Known and Objectives

Bleeding is the most common adverse reaction to aspirin and can lead to drug discontinuation or even be life-threatening in the secondary prevention of stroke or transient ischemic attack. The aim of this study was to evaluate risk factors for bleeding adverse reaction of aspirin in ischemic stroke or transient ischemic attack.

Methods

This retrospective analysis included patients treated with aspirin (100 mg) as a secondary prevention for ischemic stroke or transient ischemic attack. The bleeding events that occurred during the first year were collected, including gastrointestinal, skin, nasal cavity, gum, and urinary tract bleeding events. Then, univariate and multivariate logistic regression analyses were used to identify independent factors associated with bleeding events of aspirin.

Results and Discussion

A total of 578 patients were enrolled in this study, and 58 patients developed bleeding during the first year of secondary prevention. Body weight and combination with selective serotonin reuptake inhibitors were found to be significant risk factors for overall bleeding (p = 0.025 and 0.012). Body weight below 60 kg was a risk factor for overall bleeding and gastrointestinal bleeding events.

What is new and conclusion

Patients weighing less than 60 kg were at increased risk of bleeding with 100 mg aspirin for secondary prevention of cerebral infarction transient ischemic attack.

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