Abscopal effect in radioimmunotherapy

Abscopal effect is an interesting phenomenon in radiobiology that causes activation of immune system against cancer cells. Traditionally, this phenomenon was known as a suppressor of non-irradiated tumors or metastasis. However, it can be used as a stimulator of the immune system against primary tumor during radiotherapy. Immunotherapy, a novel tumor therapy modality, also triggers immune system against cancer. To date, some immunotherapy types have been developed. However, immune checkpoint blockade is a more common modality and some drugs have been approved by the FDA. Studies have shown that radiotherapy or immunotherapy administered alone have low efficiency for tumor control. However, their combination has a more potent anti-tumor immunity. For this aim, it is important to induce abscopal effect in primary tumors, and also use appropriate drugs to target the mechanisms involved in the exhaustion of cytotoxic CD8+T lymphocytes (CTLs) and natural killer (NK) cells. Among the different radiotherapy techniques, stereotactic body radiation therapy (SBRT) with some few fractionations is the best choice for inducing abscopal effect. On the other hand, programmed cell death 1 (PD-1) is known as one of the best targets for triggering anti-tumor immunity. This combination is known as the best choice among various strategies for radioimmunotherapy. However, there is the need for other strategies to improve the duration of immune system’s activity within tumor microenvironment (TME). In this review, we explain the cellular and molecular mechanisms behind abscopal effect by radiotherapy and evaluate the molecular targets which induce potent anti-tumor immunity.     

End-of-life practices in patients admitted to pediatric intensive care units in Brazil: A retrospective study

ObjectiveTo determine the prevalence of life support limitation (LSL) in patients who died after at least 24 h of a pediatric intensive care unit (PICU) stay, parent participation and to describe how this type of care is delivered.MethodsRetrospective cohort study in a tertiary PICU at a university hospital in Brazil. All patients aged 1 month to 18 years who died were eligible for inclusion. The exclusion criteria were those brain death and death within 24 h of admission.Results53 patients were included in the study. The prevalence of a LSL report was 45.3%. Out of 24 patients with a report of LSL on their medical records only 1 did not have a do-not-resuscitate order. Half of the patients with a report of LSL had life support withdrawn. The length of their PICU stay, age, presence of parents at the time of death, and severity on admission, calculated by the Pediatric Index of Mortality 2, were higher in patients with a report of LSL. Compared with other historical cohorts, there was a clear increase in the prevalence of LSL and, most importantly, a change in how limitations are carried out, with a high prevalence of parental participation and an increase in withdrawal of life support.ConclusionsLSLs were associated with older and more severely ill patients, with a high prevalence of family participation in this process. The historical comparison showed an increase in LSL and in the withdrawal of life support.     

Jouer avec la mort : prise de risque dans le sport et deuils impossibles

AimAlthough death seems to be increasingly dissimulated in our Western society, “death-dodger” behaviors, on the contrary, are constantly on the rise. The study of those who practice high-risk sports allows us to clearly see their game with/around/against death. Through the case of Kevin, who engages in tremendously risky behavior in his practice of sport, we propose to show how continued traumaphilia and flirting with death is an attempt to deal with multiple griefs, as well as an illusory attempt to restore a frail narcissism, weakened by losses and mournings that remain unresolved.MethodThe authors conducted a case study, with exemplary value, combining two unstructured-type research interviews as well as the administration of the Rorschach and TAT tests, with a retest one month later. These tests were analyzed according to the principles of the French school.ResultsIn addition to an identification with masculinity and virility, lethal risk-taking in sports can also be understood, in our case study, as a fight against the effects of multiple bereavements and the associated depression. This is the anti-depressive struggle that is at the forefront of psychological functioning and that becomes part of the masochism expressed in “traumaphilia,” constituting the last defense against the risk of an otherwise more disruptive collapse.DiscussionThe authors propose the notion of “sepulcher work” – borrowing R. Gori's and M.-J. Del Volgo's use of the expression, with reference to M. de M’Uzan's formula on the work of passing over – to define the stage of mourning in which it is recognized that the object has indeed been definitively lost. Sepulcher work, for us, consists in a psychological movement in which the subject who has lost her/his object admits that this loss is final: the first recognition of the principle of reality prior to the work of mourning.ConclusionsThe risk-taking in sports reported in the case studied here illustrates unique clinical situations in which the process of mourning could not begin, leading to depression. These psychopathological configurations do not constitute a homogeneous clinical picture, but illustrate, in their own way, psychological strategies to avoid facing the suffering of loss.     

Patient's Perspectives on the Notion of a Good Death: A Systematic Review of the Literature

ContextThere is no clear definition of what constitutes a good death or its features. Patients, caregivers, physicians, and relatives have different notions of a good death. Discussions have been driven by academic perspectives, with little research available on the patients' perspectives.ObjectivesTo explore the notions of a good death from the patients' perspective.MethodsA systematic literature search was conducted up to November 2017 using CINAHL®, MEDLINE®, EMBASE®, and PsycINFO® databases. Search terms used were “quality of death,” “good death,” “quality of dying,” or “good dying.” Scientific empirical studies that included the exploration of the notion of a good death in adult patients with advanced and life-threatening diseases were selected separately by two researchers. Hawker's et al. criteria were used to assess the quality of articles. The analysis was conducted using a thematic analysis.ResultsTwo thousand six hundred and fifty two titles were identified; after elimination of duplicates, screening, and final selection, 29 relevant publications remained for analysis. Sample populations included patients with terminal diseases (AIDS, cardiovascular disease, and cancer). Core elements for a “good death” included control of pain and symptoms, clear decision-making, feeling of closure, being seen and perceived as a person, preparation for death, and being still able to give something to others; whereas other factors such as culture, financial issues, religion, disease, age, and life circumstances were found to shape the concept across groups. Studies agree on the individuality of death and dying while revealing a diverse set of preferences, regarding not only particular attributes but also specific ways in which they contribute to a good death.ConclusionsAlthough sharing common core elements, patients' notions of good death are individual, unique, and different. They are dynamic in nature, fluctuating within particular groups and during the actual process of dying. Formal and informal caregivers should carefully follow-up and respect the patient's individual concepts and preferences regarding death and dying, while attending to shared core elements, to better adjust clinical decisions.     

一起尿源性脓毒血症死亡案例的解析与改进*

对一起尿源性脓毒血症患者死亡案例进行解析，从明确诊断标准、制定规范举措、畅通绿色通道、促进患方参与等方面进行改进。改进后，尿源性脓毒血症患者诊断率提高，就诊至处理时间（DTN）从88.9min缩短至55.6min（P＜0.001），患者住院时间由7.9天缩短至4.9天，人均住院总费用减少8 105元，差异均有统计学意义（P＜0.05）。运用精益管理方法，优化专科急危重症诊治流程，能够缩短治疗时间，促进患者康复，节约住院费用，改善患者愈后     

The burden of herpes zoster disease in Norway

BackgroundNo national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program.MethodsWe linked data from several health registries to identify medically attended HZ cases during 2008–2014 and HZ-associated deaths during1996–2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality.ResultsThe study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%.ConclusionsMedically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years – the group eligible for zoster vaccination – and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities.     

死亡结构域相关蛋白及其在宫颈病变中的研究进展

宫颈癌对妇女健康构成严重威胁,人乳头瘤病毒感染与宫颈病变及宫颈癌的发生密切相关。关于宫颈癌发生发展的机制仍在研究中。近年研究发现一种多功能核蛋白,即死亡结构域相关蛋白(death domain associated protein,Daxx),其与细胞内蛋白或病毒蛋白相互作用,参与调节细胞凋亡、转录调控、抗病毒等细胞活动,在不同途径中发挥不同的生理或病理作用。通过对Daxx功能及其作用机制的研究有助于进一步阐明宫颈癌发生发展的机制,有助于发现新的预防和治疗方法。综述Daxx的一般特性和研究现况及其在宫颈病变的研究进展。