First-line immunotherapy in non-small cell lung cancer patients with poor performance status: A systematic review and meta-analysis

Background: Immune checkpoint inhibitors (ICIs) have become the standard of care for the first-line treatment of advanced non-small cell lung cancer patients (NSCLC), either as single agents or combined with chemotherapy. The evidence sustaining their role for poor performance status (ECOG PS ≥2) patients is limited. Methods: We search PubMed and the proceedings of international oncology meetings to perform a systematic review to assess the outcomes poor PS NSCLC patients who received ICIs as first-line treatment. A meta-analysis included retrospective studies focusing on pembrolizumab monotherapy in PD-L1 ≥50% NSCLC. We reported the global objective response rate (ORR), disease control rate (DCR) and landmark progression-free and overall survival (PFS and OS, respectively) in ECOG PS ≥2 and 0-1 patients, respectively. Results: Forty-one studies were included in the systematic review. Thirty-two retrospective studies focused on pembrolizumab monotherapy in PD-L1 ≥50% cases. In total, 1,030 out of 5,357 (19%) of patients across 30 studies presented with a PS ≥2 at pembrolizumab initiation. In 18 studies with detailed clinical information, worse outcomes in poor PS compared to good PS patients were documented. The meta-analysis revealed that ORR and DCR within the PS ≥2 patient population were 30.9% and 41.5% respectively (55.2% and 71.5% in PS 0-1 patients). The rates of PFS (at 3, 6, 12 and 18 months) and OS (at 6, 12, 18 and 24 months) were approximately double in the good PS compared to the poor PS group of patients. In the three prospective trials where of ICIs in PS 2 populations, the diverse strictness in PS definition likely contributed to the differential outcomes observed. Six retrospective studies dealt with chemo-immunotherapy combinations. Conclusions: Still with limited prospective evidence sustaining the role of immunotherapy in previously untreated NSCLC with poor PS, 19% of patients in retrospective series dealing with pembrolizumab in PDL1 ≥50% tumors had an ECOG PS ≥2. Clinical effort encompassing the definition of poor PS, of the factors conditioning it, and the development of dedicated treatment strategies is required to improve the outcomes in this patient population

The driver’s protection in case of self-propelled machinery roll-over

Despite a real risk of overturning, for the Self-Propelled agricultural Machinery (SPM) the ROPS approach to protect the driver is rather recent. Due to the several SPM categories available on the market, characterized by very different mass, dimension and working functions, the fitting of a ROPS and consequently the check of its strength is complicated. The SPM could be preliminarily divided into at least two categories: - large SPM: combine, forage, potato, sugar-beet and grape harvesters; sprayer; etc.; - small SPM: ride-on tractor, mower, comb side-delivery rake, etc. The most followed approach at present is to define preliminarily the overturning behaviour of the SPM, considering its longitudinal and lateral stability; if a real risk is detected, in order to minimize the likelihood of driver's injury the manufacturer often decides to install a ROPS. The consequent need is to provide some relevant test criteria. Sprayers among large SPM, and comb side-delivery rake among small SPM were the machine types on which the ROPS were tested, adopting in both cases the procedure provided by Code 4 issued by the Organization for Economic and Cooperation Development (OECD), dedicated to ROPS fitted on conventional agricultural and forestry tractors. On the sprayer having a mass of 4950 kg was fitted a closed cab, while on the comb side-delivery rake having a mass of 690 kg was applied a 3-pillars frame. The response was positive in both tests, so indicating a general suitability of OECD Code 4 to assure a ROPS good driver\u2019s protection level in case of overturning. On the other hand, to ascertain more in detail the roll-over behaviour of the SPM, some further questions need to be deeply examined, such as the driver\u2019s place location, the height of the centre of gravity from the ground in different machine configurations (i.e. with product tanks empty or full), the external silhouette, the axles mass distribution of the laden/unladen machine, etc

Comfort efficiency of the front axle suspension in off-road operations of a medium-powered agricultural tractor

The whole-body vibration transmitted through the seat of a 4WD modern tractor of 81 kW max power, equipped with seat, cab and front axle suspension systems were measured and analysed according to the official relevant Standards. The test conditions involved the travelling speed (from 1.11 to 4.44 m s-1), the surface feature (field and rough track), the type of task (tractor alone and coupled with a towed slurry tank) and the front axle suspension condition (working or locked). After their statistical validation, the results highlight a good efficiency of the front axle suspension in reducing the vibration levels of the tractor alone, while when coupled with the slurry tank the benefit is less evident, especially in the back-front direction. The lower limit provided by the 2002/44 EC Directive (\u201caction value\u201d, 0.5 m s-2) is generally exceeded in all the three axes, apart when travelling at the lowest speed. Vice versa, the vibration levels exceed the higher limit (\u201climit value\u201d, 1.0 m s-2) only if the overall RMS values are considered, in the field at 2.22 m s-1 and on the rough track at 4.44 m s-1

Analysis of Hazardous Emissions of Hand-Operated Forestry Machines Fuelled with Standard Mix or Alkylate Gasoline

In addition to safety, small hand-operated forestry machines can be criticised for affecting the operators\u2019 health, especially because of high levels of exhaust gas emissions, noise and vibrations. In this study, gas emissions, noise and hand-arm vibrations (HAV) levels have been measured on chainsaws, hedge cutters and blowers fuelled with two different types of fuel: a commercial RON 95 gasoline with the addition of 2% of synthetic oil suitable for two-stroke engines and, as an alternative, a specific advanced mixture available on the market, based on alkylate gasoline. For two different running conditions, i.e. with the engine at idle speed and when executing a typical working routine (maximum speed with load), tests were carried out for: \u21d2 ggas emissions, using a gas analyser, for measuring the volatile organic compounds (VOC) values \u21d2 gnoise, using a sound level meter, to record the levels at both of the operator\u2019s ears \u21d2 gHAV, using a tri-axial accelerometer fixed on the handgrip(s) of the machines. The results demonstrated that, when using the alkylate fuel, the VOC emissions were reduced, in the considered machines, from 23 to over 77%, while for noise and HAV, the differences in level were not statistically significant. The present study confirms that the reduction in the amount of emissions can be remarkably improved by adopting advanced fuels that lead to a more efficient combustion process

Aqueye optical observations of the Crab Nebula pulsar

We observed the Crab pulsar in October 2008 at the Copernico Telescope in Asiago - Cima Ekar with the optical photon counter Aqueye (the Asiago Quantum Eye) which has the best temporal resolution and accuracy ever achieved in the optical domain (hundreds of picoseconds). Our goal was to perform a detailed analysis of the optical period and phase drift of the main peak of the Crab pulsar and compare it with the Jodrell Bank ephemerides. We determined the position of the main peak using the steepest zero of the cross-correlation function between the pulsar signal and an accurate optical template. The pulsar rotational period and period derivative have been measured with great accuracy using observations covering only a 2 day time interval. The error on the period is 1.7 ps, limited only by the statistical uncertainty. Both the rotational frequency and its first derivative are in agreement with those from the Jodrell Bank radio ephemerides archive. We also found evidence of the optical peak leading the radio one by ~230 microseconds. The distribution of phase-residuals of the whole dataset is slightly wider than that of a synthetic signal generated as a sequence of pulses distributed in time with the probability proportional to the pulse shape, such as the average count rate and background level are those of the Crab pulsar observed with Aqueye. The counting statistics and quality of the data allowed us to determine the pulsar period and period derivative with great accuracy in 2 days only. The time of arrival of the optical peak of the Crab pulsar leads the radio one in agreement with what recently reported in the literature. The distribution of the phase residuals can be approximated with a Gaussian and is consistent with being completely caused by photon noise (for the best data sets).Comment: 7 pages, 7 figures. Accepted for publication in Astronomy and Astrophysic

Stillbirth occurrence during COVID-19 pandemic: A population-based prospective study

Objectives: Data collected worldwide on stillbirth (SB) rates during the Covid-19 pandemic are contradictory. Variations may be due to methodological differences or population characteristics. The aim of the study is to assess the changes in SB rate, risk factors, causes of death and quality of antenatal care during the pandemic compared to the control periods. Methods: This prospective study is based on the information collected by the Emilia-Romagna Surveillance system database. We conducted a descriptive analysis of SB rate, risk factors, causes of death and quality of cares, comparing data of the pandemic (March 2020-June 2021) with the 16 months before. Results: During the pandemic, the SB rate was 3.45/1,000 births, a value in line with the rates of previous control periods. Neonatal weight >90th centile was the only risk factor for SB that significantly changed during the pandemic (2.2% vs. 8.0%; p-value: 0.024). No significant differences were found in the distribution of the causes of death groups. Concerning quality of antenatal cares, cases evaluated with suboptimal care (5.2%) did not change significantly compared to the control period (12.0%), as well as the cases with less than recommended obstetric (12.6% vs. 14%) and ultrasound evaluations (0% vs. 2.7%). Conclusions: During the COVID-19 pandemic, no significant differences in SB rates were found in an area that maintained an adequate level of antenatal care. Thus, eventual associations between SB rate and the COVID-19 infection are explained by an indirect impact of the virus, rather than its direct effect

Induction of Labor According to Medical Indications: A Critical Evaluation through a Prospective Study

Background: The induction of labor (IOL) is a common obstetric intervention, steadily increasing (one out four pregnancies) in the last years. This procedure should be considered only when there is a medical indication, and when the benefits outweigh the maternal and/or fetal risks of waiting for spontaneous onset of labor. Therefore, this study aims to compare the efficacy of the IOL in terms of induction to delivery time, mode of delivery, and neonatal well-being among different evidence-based and non-evidence-based indications. Methods: This prospective study was conducted at the University Hospital of Modena, between January and December 2020. We included singleton pregnant women undergoing IOL, at the term. Intrauterine deaths, small for gestational age fetuses <5th centile as well women with hypertensive disorders were excluded. Women have been subdivided into 3 groups based on the indication to IOL: premature rupture of membranes (PROM), post-date pregnancy (>41 weeks + 3 days), and non-evidence-based indications (NEBI). The primary outcome is the time occurring between IOL and delivery (TIME), analyzing separately by parity. Moreover, mode of delivery and neonatal wellbeing were evaluated. Results: A total of 585 women underwent IOL in the study period. Overall, the median TIME between IOL and delivery was 19 hours, and the mean cesarean section CS rate was 15.5% (91/585). Pregnancies induced for postdate and non-evidencebased indications registered respectively a significantly higher mean time (p < 0.001), compared with women induced for PROM. This occurred both in nulliparous and multiparous women. Moreover, at multivariate analysis, the IOL TIME ≥24 hours was significantly influenced by Bishop score (p = 0.000) and NEBI (p = 0.02) in nulliparous and by gestational age (p = 0.000) and NEBI (p = 0.02) in multiparous. Moreover, CS rate was significantly influenced by Bishop score (p = 0.003) in nulliparous and by gestational age (p = 0.01) in multiparous. Finally, neonatal intensive care unit (NICU) admission resulted significantly influenced only by gestational age (p = 0.002) in multiparous. Conclusions: Our study confirms that IOL in non-evidence-based indications, leads to an increase in induction to delivery time comparing with women induced for PROM, both in nulliparous and multiparous women, thus it should be justified and carefully evaluated. Further randomized controlled trials (RCT) conducted in European/Italian settings are needed to determine the perinatal outcomes of IOL in non-evidence-based indications

Mode of Delivery in Women with Stillbirth: Results of an Area-Based Italian Prospective Cohort Study

Introduction: The choice of the mode of delivery, in case of stillbirth (SB) (fetus non-viable >22 weeks' gestation), should consider maternal preference, gestational age, bishop score, the clinical condition of the woman, and her previous obstetric history. However, despite these clear indications, data on the effective implementation of the latter are lacking. The aim of our study is to evaluate the different modes of delivery in an Italian population of SBs, according to gestational age, parity, causes of death, obstetric history, and maternal characteristics. Material and Methods: This is an area-based, prospective cohort study conducted in Emilia Romagna, Italy between January 2014 to December 2020. Data included all cases of SB (>22 weeks). Results: From 2014 to 2020, 783 SB occurred out of a total of 232.506 births, with a SB rate of 3.3 per 1000. Labor was spontaneous in 85 (11%). Of remnant, 567 (73.6%) were induced and 118 (15.3%) had no labor. The mode of delivery was vaginal in most of the cases (649/770, 84.3%) and by cesarean section in 121/770 (15.7%) of cases. Emergency CS was most frequent and performed in 89/121 (73.5%) of total CS, representing 11.5% of SB deliveries. Mode of induction did not differ in relation to gestational age at stillbirth, while vaginal delivery was significantly higher in women induced with prostaglandins (p = 0.000) respect to other methods. Nulliparous women had a significantly higher need for multiple methods of induction (p = 0.000) respect multiparous and obese women used more frequently prostaglandins (p = 0.03) than other methods. Women with a history of previous CS presented a significantly higher rate of repeated elective CS (p = 0.000). Moreover, emergency CS was performed more frequent in obese (p = 0.02), diabetic (p = 0.04) and hypertensive (p = 0.04) women and in SB caused by placenta disorders, namely in abruptio placentae (p = 0.000). In the case of chorioamnionitis and funisitis women significantly were induced with prostaglandin (p = 0.000) and delivered vaginally (p = 0.000). Conclusions: The method of induction of labor and the mode of delivery in case of SB did not depend on gestational age at the diagnosis of death, while they are related to placenta disorders representing a relevant condition leading to emergency CS also after diagnosis of fetal death. These data could help obstetric providers in managing the deliveries of stillborn infants