Il presente articolo propone il confronto delle tre versioni del fabliau La housse partie, partendo da alcune considerazioni riguardanti i motivi letterari che permeano i componimenti e ...l’appartenenza degli stessi al genere fabliolostico. Il confronto dei tre testi ha messo in luce elementi interessanti di questo fabliau da un punto di vista narratologico e letterario, ma anche peculiarità che hanno diviso la critica, come il suo carattere moraleggiante, i personaggi messi in scena e il tipo di pubblico al quale si rivolge. Infine, lo studio approfondito de La housse partie ha permesso di formulare ipotesi circa la circolazione di questa storia in epoca medievale, la sua destinazione e il suo scopo.
•Immunotherapy changed treatment paradigm for NSCLC patients.•Real-world patients often differ from selected patients enrolled in clinical trials.•Some patient subsets are underrepresented in ...randomized clinical trials (RCTs)•Real-world studies may close this gap and overcome the intrinsic limits of RCTs.
Immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) quickly subverted the standard of treatment in Non-Small Cell Lung Cancer (NSCLC), where they were first introduced in all comers previously treated advanced/metastatic NSCLC patients and subsequently in the first line of PD-L1 selected cases of metastatic and locally advanced disease.
Treatment algorithm is an evolving landscape, where the introduction of front-line ICIs, with or without chemotherapy, unavoidably influences the following treatment lines. In this context, medical oncologists are currently facing many unclear issues, which have been not clarified so far by available data.
Effectiveness and safety in special populations underrepresented in clinical trials - such as elderly, poor PS, hepatitis or human immunodeficiency virus-affected patients - are only a part of the unexplored side of ICIs in the real world. Indeed, pivotal randomized clinical trials (RCTs) often lack of external validity because eligibility criteria exclude some patient subgroups commonly treated in real-world clinical practice. Similarly, cost-effectiveness and sustainability of these innovative agents are important issues to be considered in the real-world. Though affected by several limitations, real-world evidence (RWE) studies allow to collect data regarding overall treated patients in clinical practice according to local authority regulations, overcoming the intrinsic limits of RCTs.
The present review focuses on RWE about ICIs in lung cancer treatment, with particular reference to special patient populations, and discusses potential application of real-world data in a potential innovative drug development model.
Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was ...found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA.
Patients with resected stages IB to IIIA EGFRm NSCLC were randomized 1:1 to receive osimertinib or placebo for 3 years. Adjuvant chemotherapy before randomization was not mandatory, per physician and patient choice. DFS in the overall population (IB–IIIA), with and without adjuvant chemotherapy, was a prespecified analysis. Exploratory analyses included the following: adjuvant chemotherapy use by patient age, disease stage, and geographic location; DFS by adjuvant chemotherapy use and disease stage.
Overall, 410 of 682 patients (60%) received adjuvant chemotherapy (osimertinib, n = 203; placebo, n = 207) for a median duration of 4.0 cycles. Adjuvant chemotherapy use was more frequent in patients: aged less than 70 years (338 of 509; 66%) versus more than or equal to 70 years (72 of 173; 42%); with stages II to IIIA (352 of 466; 76%) versus stage IB (57 of 216; 26%); and enrolled in Asia (268 of 414; 65%) versus outside of Asia (142 of 268; 53%). A DFS benefit favoring osimertinib versus placebo was observed in patients with (DFS hazard ratio = 0.16, 95% confidence interval: 0.10–0.26) and without adjuvant chemotherapy (hazard ratio = 0.23, 95% confidence interval: 0.13–0.40), regardless of disease stage.
These findings support adjuvant osimertinib as an effective treatment for patients with stages IB to IIIA EGFRm NSCLC after resection, with or without previous adjuvant chemotherapy.
Liver kinase B1 (
) is a tumor suppressor gene whose inactivation is frequent in different tumor types, especially in lung adenocarcinoma (about 30% of cases). LKB1 has an essential role in the ...control of cellular redox homeostasis by regulating ROS production and detoxification. Loss of LKB1 makes the tumor cell more sensitive to oxidative stress and consequently to stress-inducing treatments, such as chemotherapy and radiotherapy. LKB1 loss triggers complex changes in tumor microenvironment, supporting a role in the regulation of angiogenesis and suggesting a potential role in the response to anti-angiogenic treatment. On the other hand, LKB1 deficiency can promote an immunosuppressive microenvironment and may be involved in primary resistance to anti-PD-1/anti-PD-L1, as it has been reported in lung cancer. The aim of this review is to discuss interactions of LKB1 with the tumor microenvironment and the potential applications of this knowledge in predicting response to treatment in lung cancer.
Fluid resuscitation in the management of patients with sepsis and severe sepsis has been considered the standard of care for almost 2 decades. The rationale for fluid resuscitation is related to ...improvement in cardiac output and organ perfusion. Recent research evidence challenges the use of fluid resuscitation in patients diagnosed with sepsis. Research is needed to determine the timing of fluid administration, as well as the volume and type of fluid to achieve positive patient outcomes. This article discusses the pros and cons of early fluid administration in the management of patients with sepsis.
Background Effective teamwork in the operating room (OR) is often undermined by the “silo mentality” of the differing professions. Such thinking is formed early in one's professional experience and ...is fostered by undergraduate medical and nursing curricula lacking interprofessional education. We investigated the immediate impact of conducting interprofessional student OR team training using high-fidelity simulation (HFS) on students' team-related attitudes and behaviors. Study Design Ten HFS OR interprofessional student team training sessions were conducted involving 2 standardized HFS scenarios, each of which was followed by a structured debriefing that targeted team-based competencies. Pre- and post-session mean scores were calculated and analyzed for 15 Likert-type items measuring self-efficacy in teamwork competencies using the t -test. Additionally, mean scores of observer ratings of team performance after each scenario and participant ratings after the second scenario for an 11-item Likert-type teamwork scale were calculated and analyzed using one-way ANOVA and t -test. Results Eighteen nursing students, 20 nurse anesthetist students, and 28 medical students participated in the training. Statistically significant gains from mean pre- to post-training scores occurred on 11 of the 15 self-efficacy items. Statistically significant gains in mean observer performance scores were present on all 3 subscales of the teamwork scale from the first scenario to the second. A statistically significant difference was found in comparisons of mean observer scores with mean participant scores for the team-based behaviors subscale. Conclusions High-fidelity simulation OR interprofessional student team training improves students' team-based attitudes and behaviors. Students tend to overestimate their team-based behaviors.
Team debriefing is an important teamwork development intervention for improving team outputs in healthcare. Debriefing is a key component of experiential team training teamwork development ...interventions such as simulation-based training. Improving the quality of debriefing of healthcare teams, therefore, has multiple benefits. We investigated whether the quality of student-led debriefing improved using a shortened guide.
Senior medical students, nurse anesthesia students, and senior undergraduate nursing students participated in student operating room team training at a health sciences center in the southeastern United States. Student teams participated in a dual-scenario simulation-based training session with immediate after-action debriefings after each scenario. In 2018, student teams conducted the second debriefing using as a guide the teamwork assessment scale, an 11-item, 3-subscale, 6-point Likert-type instrument. In 2019, they used a shortened, revised, 5-item version of the teamwork assessment scale, the quick teamwork assessment scale. Trained observers rated the quality of the student-led debriefings using the Objective Structured Assessment of Debriefing, an 8-item, 5-point instrument. The Wilcoxon-Mann-Whitney test was used to compare the teamwork assessment scale-guided and the quick teamwork assessment scale-guided mean item debriefing scores.
Two observers rated 3 student-led team debriefings using the teamwork assessment scales as a guide in 2018, and 6 such debriefings happened using the quick teamwork assessment scale as a guide in 2019. For each debriefing, observer scores were averaged for each Objective Structured Assessment of Debriefing item; these mean scores were then averaged with other mean scores for each year. The use of the quick teamwork assessment scale resulted in a statistically significant higher mean score for the Analysis Objective Structured Assessment of Debriefing item compared with the use of the teamwork assessment scale (4.92 standard deviation 0.20 versus 3.83 standard deviation 0.76, P = .023).
The use of a shortened teamwork assessment instrument as a debriefing guide for student teams in student operating room team training was more effective in analysis of actions than the original, longer tool. Next steps include determining the efficacy of the quick teamwork assessment scale in an actual clinical setting.
The prevalence of pulmonary hypertension (PH) has risen in adults of all races, genders, and ethnicities. PH is a fatal disease that presents many challenges to the perioperative health care team. ...Through increased knowledge of PH pathophysiological changes and anesthesia medications' effect on PH, perioperative health care teams can conduct a detailed preoperative evaluation to determine appropriate therapies to administer. This will assist the perioperative health care team in reducing the pulmonary vascular resistance, optimizing the matching of right ventricle and pulmonary circulations, and reduce the incidence of intraoperative and postoperative complications.
Extensive stage-Small-Cell Lung Cancer (ES-SCLC) is an aggressive cancer with dismal prognosis. The addition of immune-checkpoint inhibitors (ICIs) to platinum-based chemotherapy have been ...consistently demonstrated to improve outcomes and survival, becoming the new standard in first - line treatment of ES-SCLC patients. However, despite positive results reported in the pivotal trials, longer benefit appears evident only for a selected group of patients. Several predictive biomarkers have been studied so far but the prospective identification of patients more likely to experience better outcome seems to be challenging in SCLC. Indeed, classical immune predictive biomarkers as PD-L1 and tumor mutational burden (TMB) seem not to correlate with outcomes. Recently, a new molecular classification of SCLC based on differential expression of genes associated with specific clinical behaviors and therapeutic vulnerability have been presented suggesting a new field to be investigated. Despite the achievements, these studies focused mainly on inter-tumoral heterogeneity, limiting the exploration of intra-tumoral heterogeneity and cell to cell interactions. New analysis methods are ongoing in order to explore subtypes plasticity. Analysis on single biopsies cannot catch the whole genomic profile and dynamic change of disease over time and during treatment. Moreover, the availability of tissue for translational research is limited due to the low proportion of patients undergoing surgery. In this context, liquid biopsy is a promising tool to detect reliable predictive biomarkers. Here, we reviewed the current available data on predictive role of tissue and liquid biomarkers in ES-SCLC patients receiving ICIs. We assessed latest results in terms of predictive and prognostic value of gene expression profiling in SCLC. Finally, we explored the role of liquid biopsy as a tool to monitor SCLC patients over time.
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