Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Statistical Mechanics-Based Schrödinger Treatment of Gravity.

The entropic gravity conception proposes that what has been traditionally interpreted as unobserved dark matter might be merely the product of quantum effects. These effects would produce a novel sort of positive energy that translates into dark matter via E = m c 2 . In the case of axions, this perspective has been shown to yield quite sensible, encouraging results [DOI:10.13140/RG.2.2.17894.88641]. Therein, a simple Schrödinger mechanism was utilized, in which his celebrated equation is solved with a potential function based on the microscopic Verlinde's entropic force advanced in [Physica A 511 (2018) 139]. In this paper, we revisit this technique with regards to fermions' behavior (specifically, baryons).

Strong correlations between the exponent α and the particle number for a Renyi monoatomic gas in Gibbs' statistical mechanics.

Appealing to the 1902 Gibbs formalism for classical statistical mechanics (SM)-the first SM axiomatic theory ever that successfully explained equilibrium thermodynamics-we show that already at the classical level there is a strong correlation between Renyi's exponent α and the number of particles for very simple systems. No reference to heat baths is needed for such a purpose.

Reply to "Comment on 'Troublesome aspects of the Renyi-MaxEnt treatment' ".

This Reply is intended as a refutation of the preceding Comment [Oikonomou and Bagci, Phys. Rev. E 96, 056101 (2017)10.1103/PhysRevE.96.056101] on our paper [Plastino et al., Phys. Rev. E 94, 012145 (2016).1539-375510.1103/PhysRevE.94.012145]. We show that the Tsallis probability distribution of our paper does not coincide with the Tsallis distribution studied by Oikonomou and Bagci. Consequently, their findings do not apply to our paper.

Troublesome aspects of the Renyi-MaxEnt treatment.

We study in great detail the possible existence of a Renyi-associated thermodynamics, with negative results. In particular, we uncover a hidden relation in Renyi's variational problem (MaxEnt). This relation connects the two associated Lagrange multipliers (canonical ensemble) with the mean energy 〈U〉 and the Renyi parameter α. As a consequence of such relation, we obtain anomalous Renyi-MaxEnt thermodynamic results.

Structure of the Tortricid-Parasitoid Community in a Recently Introduced Crop.

The introduction of exotic commercial plants represents a change in the food resources for the communities of herbivores. The blueberry is native to the northern hemisphere and was recently introduced in Argentina, so we expect to find polyphagous tortricids and a low complexity in the tortricid-parasitoid community. Tortricids are exophytic leaf-rollers and flower and fruit feeders, they can feed on different plant structures, and they may be present in every blueberry phenological stage. The aims of this study were (a) to estimate the relative abundance of tortricids in different plant structures and phenological stages of blueberry, (b) to evaluate the relative importance of the different parasitoid guilds, and (c) to describe the tortricid-parasitoid community in blueberry fields of Argentina. The abundance of tortricids in blueberries was low and mainly localized to flowers and fruits. Five parasitoid guilds were identified: early larval endoparasitoids (Apanteles sp. and Dolichogenidea m1 and m2), larval-prepupal endoparasitoids (Austroearinus sp.), larval-pupal endoparasitoids (Ichneumonidae), larval ectoparasitoids (Eulophidae), and pupal endoparasitoids (Brachymeria sp. and Conura sp.). Most parasitoids were koinobiont larval endoparasitoids. The tortricid-parasitoid food web was very simple in comparison to those of other systems, with high values of vulnerability and connectance. The results of this study suggest that the abundance of tortricids in blueberry crop in Argentina is low. From the point of view of production, the risk of economic losses and the likelihood of direct damage to the fruit would be very low.

Ultrasound-guided internal jugular vein catheterization: a randomized controlled trial.

INTRODUCTION: Even though advantages of ultrasound line placement seem obvious, many countries do not have easy access to such technology. This study aims to compare the degree of difficulty in central venous line placement with or without ultrasound and the incidence of complications, and to establish the effect of the operator's degree of training. METHODS: The study included 257 patients that required central venous catheterization during the study period. Patients were divided into groups according to the operator's experience: expert group (over 70 central accesses performed before the study) (n=152) and in-training or non-expert group. Procedures were randomized to "without ultrasound" (n=80 expert and 54 non-expert) and "with ultrasound" (n=72 expert and 51 non-expert). RESULTS: Catheter placements were more successful in the "expert" and in the "with ultrasound" than in the "non-expert" (88% vs 79%; p=0.04) or in the "without ultrasound" groups (91% vs 78%; p=0.005). Incidence of complications was 11.7%, with no significant difference among "with ultrasound" (8.1%) and "without ultrasound" (14.9%) groups. However, the "non-expert" group had fewer complications with the use of ultrasound (7.8% vs 24%). CONCLUSIONS: Ultrasound reduces the incidence of complications when placement is performed by inexperienced operators. Centers with residents should emphasize the necessity of ultrasound for central line catheterization. Training in ultrasound might be of paramount importance in the effectiveness of the technique.

Sistema de liberação prolongada a partir de comprimidos matriciais bioadesivos vaginais contendo metronidazol / Sustained release system from vaginal bioadhesive matrix tablets containing metronidazole

A vaginose bacteriana é a mais comum das infecções do trato genital feminino.O metronidazol, droga de escolha no tratamento, possui boa resposta terapêutica, mas, devido à sua toxicidade após doses contínuas, tem sua capacidade de combate e reversão da doença limitada pela efemeridade do tratamento.Desenvolveu-se a forma farmacêutica comprimido matricial bioadesivo vaginal contendo metronidazol que levou em conta, tanto a redução das quantidades administradas da droga, quanto o uso de atributos que desfavoreçam a permanência da flora patógena no meio vaginal, como a liberação prolongada e a acentuada adesão da forma à mucosa.Foram obtidos durante o estudo três formulações chamadas de lotes de bancada (LB I, LB II e LB III) com variações quali-quantitativas dos excipientes utilizados.Nos LB I e LB II utilizou-se o hidropropilmetilcelulose e carbopol como constituintes da matriz, porém no LB III foi utilizado uma composição de hidropropilmetilcelulose, etilcelulose e carbopol.As formulações apresentaram resultados dentro das especificações frente aos testes físico-químicos habituais de acordo com a Farmacopéia brasileira.Os comprimidos LB I e LB II liberaram todo seu conteúdo após seis e 12 horas, respectivamente, a partir de matrizes de caráter notadamente adesivo e ao fim dos ensaios mantiveram-se na forma de pequena estrutura gelificada.Mesmo sob essas condições, e após 48 horas de ensaio, a formulação LB III não liberou todo seu conteúdo, pode-se levar em conta a mudança da natureza dos componentes da matriz assim como a necessidade de um desenvolvimento e validação de método mais específico para dissolução