Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases.

Background: Long-term data with immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti-programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and nonsquamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC. Patients and methods: Patients were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or discontinuation. The primary end point of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses. Results: After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% [95% confidence interval (CI), 14% to 21%] versus 8% (95% CI, 6% to 11%) in the pooled population with squamous or nonsquamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50-0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61-0.81). Rates of treatment-related hepatic adverse events (primarily grade 1-2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%). Conclusions: After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated. Clinical trial registration: CheckMate 017: NCT01642004; CheckMate 057: NCT01673867.

High dose irradiation after pleurectomy/decortication or biopsy for pleural mesothelioma treatment.

PURPOSE: The role played by radiation therapy after pleurectomy/decortication or surgical biopsy in malignant pleural mesothelioma is uncertain. We treated patients with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy in an attempt to keep lung toxicity to a minimum. The present study reports the feasibility and toxicity of this approach. MATERIAL AND METHODS: Between 2008 and 2012, 36 patients with malignant pleural mesothelioma underwent accelerated hypofractionated radiotherapy to the hemithorax after pleurectomy/decortication (19 patients) or biopsy (17 patients). The prescription dose was 25Gy in five fractions over 5 consecutive days. RESULTS: We observed three patients with G3 pneumonitis, five cases of grade 2 dyspnea and six cases of grade 2 cough. The median follow-up was 37 months (range: 3-54 months). The median overall survival for patients who underwent pleurectomy/decortication followed by radiotherapy was 21.6 months [95% confidence interval (95% CI): 15.5-24.1] compared to 19.4 months for patients not submitted to surgery. CONCLUSION: Treatment of intact lung with pleural intensity-modulated arc irradiation in malignant pleural mesothelioma patients with malignant pleural mesothelioma proved safe and feasible, with an acceptable rate of pneumonitis. Survival rates were encouraging for both biopsy-only and pleurectomy/decortication groups. We are currently conducting a phase II dose escalation trial in a similar patient setting to prospectively evaluate the impact of radiotherapy on toxicity, disease-free survival and overall survival.

Management of the second phase of labour: perineum protection techniques.

The obstetric experience alongside scientific evidences in literature indicate several management techniques during the expulsive period of labour to minimize obstetric complications. Among the various methods that can be used for the protection of the perineum during the expulsive phase, some are performed prepartum (perineum massage), while most are used during childbirth. Among the second group, progressively increasing importance is assumed by the manual techniques to protect the perineum (using the "hands-on" and "hands-off") and by episiotomy. These techniques, when used in accordance to the guidelines, may favour the reduction of adverse outcomes for both the mother and the newborn, both immediately after birth and after a longer time. The midwife should be aware of the evidences in literature so that a critical analysis of the available techniques can be made and put in action during the expulsive phase in order to protect the mother and the foetus from any unfavourable outcomes. Currently, clinical evidence in literature is directing obstetric and medical staff towards a careful analysis of the maternal-foetal parameters, in order to achieve a precise assessment of the risks factors of intrapartum and postpartum outcomes. Increasingly, there is the need for close collaboration between the midwife and medical staff to ensure proper personalized assistance based on the peculiar characteristics of the woman and the fetus.

Evaluation of recovery and quality of sexual activity in women during postpartum in relation to the different mode of delivery: a retrospective analysis.

AIM: Aim of the study was to assess the recovery and quality of sexual activity of women during postpartum, in relation to delivery. METHODS: We recruited 200 women at 8 weeks after delivery. For each patient we recorded mode of delivery, age, body mass index (BMI), parity and test Female Sexual Function Index (FSFI) score. RESULTS: Sixty-four women (32%) had spontaneous deliveries without episiotomy, 48 (24%) had it with episiotomy, 88 (44%) had caesarean sections. The analysis of variance (ANOVA) test showed no significant differences among the 3 groups for age, BMI, parity. The test FSFI evidenced 68 cases (34%) of Regular Female Sexual Function (RFSF) and 132 (66%) of Female Sexual Dysfunction (FSD). The ANOVA test showed significant differences among the 3 groups in RFSF (F [2, 14]=8.075, P=0.005), but not in FSD (F [2, 30]=2.646, P=0.087). In RFSF, FSFI score was higher in women who had vaginal delivery with episiotomy compared with the other two groups. Conversely, in FSD (both with or without resumed sexual activity at 8 weeks postpartum) we evidenced that patients who had vaginal delivery with episiotomy showed lower FSFI score than the other two groups, with a decrease in lubrication, orgasm and satisfaction scores. Furthermore, we observed that most of the RFSF patients had a job and breastfed. CONCLUSION: Our results did not evidence a direct and significant correlation between mode of delivery and onset of female postpartum sexual dysfunction, even if FSD patients who underwent episiotomy during delivery markedly showed low FSFI scores.

Analysis of the Influence of Lunar Cycle on the Frequency of Spontaneous Deliveries: A Single-centre Retrospective Study.

BACKGROUND: Man, since ancient times, has been convinced of, and has researched scientific evidence that the barometric and gravitational forces play an important role in structural and biological variation of the planets, influencing the various forms of life. In particular, the synergistic relationships between variations in atmospheric pressure and gravitational forces on human gestation period have been the subject of rigorous observations and statistical calculations, which have not led to a universal conclusion in literature. OBJECTIVES: The aim of our work was to check whether there is a higher incidence of spontaneous deliveries, during the periods of full Moon than during the other phases of the Moon. METHODS: We performed a retrospective analysis of 327 non-induced vaginal deliveries in a year, divided by month. We subsequently analyzed the incidence of these deliveries during periods of full Moon Vs other lunar phases. RESULTS: We evidenced a statistically significant difference between the annual total spontaneous deliveries happened in full Moon periods Vs all other Moon phases (T= 2,3948; p=0,0256). However, we reported a discordant trend of deliveries in full Moon period, depending on each considered month. CONCLUSION: Since these differences were found both in increase and decrease, it is unacceptable the assumption of a linear correlation between periods of full Moon and increased frequency of spontaneous deliveries. For this reason, our data allow us to conclude that there is no need to increase the number of doctors and midwives in obstetric units during these periods.