Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC). Methods. From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0. Results. Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules. Conclusions. This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients

Isolated Meningitis and Lacrimal Gland Abscess due to Odontogenic Sinusitis: Case Report

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Heart rate detection by Fitbit ChargeHR™: A validation study versus portable polysomnography

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66(0.04)beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r=0.85±0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r=0.9662; N1, r=0.9918; N2, r=0.9793; N3, r=0.9849) than in wakefulness (r=0.8432). Moreover, the correlation coefficient was lower for HRs of &gt;100bpm (r=0.374) than for HRs of &lt;100bpm (r=0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions

Age is not the only risk factor in COVID-19: the role of comorbidities and of long staying in residential care homes

Background: The actual SARS-CoV-2 outbreak caused a highly transmissible disease with a tremendous impact on elderly people. So far, few studies focused on very elderly patients (over 80 years old). In this study we examined the clinical presentation and the outcome of the disease in this group of patients, admitted to our Hospital in Rome. Methods: This is a single-center, retrospective study performed in the Sant’Andrea University Hospital of Rome. We included patients older than 65 years of age with a diagnosis of COVID-19, from March 2020 to May 2020, divided in two groups according to their age (Elderly: 65–80 years old; Very Elderly &gt; 80 years old). Data extracted from the each patient record included age, sex, comorbidities, symptoms at onset, the Pneumonia Severity Index (PSI), the ratio of the partial pressure of oxygen in arterial blood (PaO2) to the inspired oxygen fraction (FiO2) (P/F) on admission, laboratory tests, radiological findings on computer tomography (CT), length of hospital stay (LOS), mortality rate and the viral shedding. The differences between the two groups were analyzed by the Fisher’s exact test or the Wilcoxon signed-rank test for categorical variables and the Mann-Whitney U test for continuous variables. To assess significance among multiple groups of factors, we used the Bonferroni correction. The survival time was estimated by Kaplan-Meier method and Log Rank Test. Univariate and Multivariate logistic regression were performed to estimate associations between age, comorbidities, provenance from long-stay residential care homes (LSRCH) s and clinical outcomes. Results: We found that Very Elderly patients had an increased mortality rate, also due to the frequent occurrence of multiple comorbidities. Moreover, we found that patients coming from LSRCHs appeared to be highly susceptible and vulnerable to develop severe manifestations of the disease. Conclusion: We demonstrate that there were considerable differences between Elderly and Very Elderly patients in terms of inflammatory activity, severity of disease, adverse clinical outcomes. To establish a correct risk stratification, comorbidities and information about provenience from LSRCHs should be considered

The path from trigeminal asymmetry to cognitive impairment: a behavioral and molecular study

Trigeminal input exerts acute and chronic effects on the brain, modulating cognitive functions. Here, new data from humans and animals suggest that these effects are caused by trigeminal influences on the Locus Coeruleus (LC). In humans subjects clenching with masseter asymmetric activity, occlusal correction improved cognition, alongside with reductions in pupil size and anisocoria, proxies of LC activity and asymmetry, respectively. Notably, reductions in pupil size at rest on the hypertonic side predicted cognitive improvements. In adult rats, a distal unilateral section of the trigeminal mandibular branch reduced, on the contralateral side, the expression of c-Fos (brainstem) and BDNF (brainstem, hippocampus, frontal cortex). This counterintuitive finding can be explained by the following model: teeth contact perception loss on the lesioned side results in an increased occlusal effort, which enhances afferent inputs from muscle spindles and posterior periodontal receptors, spared by the distal lesion. Such effort leads to a reduced engagement of the intact side, with a corresponding reduction in the afferent inputs to the LC and in c-Fos and BDNF gene expression. In conclusion, acute effects of malocclusion on performance seem mediated by the LC, which could also contribute to the chronic trophic dysfunction induced by loss of trigeminal input

Long-term cyclic intravenous iloprost in systemic sclerosis: clinical experience from a single center

The aim of the present study was to retrospectively evaluate response to therapy in 73 patients affected by systemic sclerosis (SSc) who underwent long-term cyclic treatment with intravenous iloprost for peripheral vascular involvement (average duration of treatment 54.12±41.04 months). Seventy-three SSc patients were enrolled. Data were collected by reviewing clinical records and by phone or direct interview. Patients underwent a thorough physical examination at the end of follow up. The incidence of severe vascular manifestations was also assessed. Statistical analysis was performed by Wilcoxon's signed rank test and descriptive statistics using Statview software. In this study cohort, 55 of 73 (75.2%) patients had a history of ischemic digital ulcers (DUs); 28 patients (38.4%) had active DUs at the beginning of treatment. Skin ulcers healed completely in 25 of 28 patients (89.3%) at the end of the first treatment. However, 40 of 55 patients (72.6%) relapsed after an average of 24 months. There was a significant correlation between relapse rate and/or number of ulcers and clinical factors (diffuse subset, changes in results of Allen's test, NT-pro BNP levels). The annual incidence of pulmonary arterial hypertension (PAH) was 2.34 (95%CI: 0.94-4.83) per 100 person years, the rate of gangrene was 2.7%, and no cases of scleroderma renal crisis were recorded. The incidence of PAH and of digital gangrene was higher than that observed in unselected SSc case series. These data suggest that our patients treated with iloprost have a higher vascular involvement than large case series of unselected SSc patients. A number of clinical factors are correlated to the severity of vascular involvement and could have an impact on the response to therapy. The clinical significance of these findings requires clarification and further investigation is needed

S.13.1 Safety and efficacy of rituximab in SSc: an analysis from the European Scleroderma Trial and Research Group

Objectives. Objective of this multicentre, observational study was to assess effects and safety of rituximab (RTX) using the European Scleroderma Trial and Research Group (EUSTAR) cohort. Methods. EUSTAR centres were asked to provide specific data about SSc patients treated with RTX. Primary endpoints were predefined for different disease manifestations and compared between baseline and follow-up. Normally distributed data, analysed by paired t-test, are shown as mean (s.d.), and non-parametric data, analysed by Wilcoxon matched paired signed-rank test, are shown as median and interquartile range. Results. Data on 72 SSc patients treated with RTX were captured from 27 EUSTAR centres (51 females/21 males, 52 diffuse/19 limited, age 51 (44-60) years, disease duration 6 (3-10) years, 47 anti-Scl-70 positive). The most frequent RTX application scheme was 1000 mg × 2 within 2 weeks (57/72 patients). Co-treatment with other immunosuppressive drugs was reported in 28 patients. The modified Rodnan skin score (mRSS) significantly decreased vs baseline at 7 (5-9) months follow-up (n = 47, 18.2 + 10.9 vs 14.5 + 9.9, P = 0.0002). This was true for both patients with later disease stages and also for patients with earlier, extended skin fibrosis (dSSc with mRSS >16 at baseline, n = 26; 26.5 + 6.8 vs 20.4 + 8.9, P < 0.0001, reduction by 29.9%). S-HAQ was unchanged, but the European SSc activity score improved after rituximab treatment [n = 10; 3.7 (2.6-6.4) vs 1.7 (0.9-2.5), P = 0.01]. RTX had no effects on lung fibrosis (FVC, DLCO, TLC, HRCT score) in n = 11 patients with evidence for SSc-ILD. In SSc-polyarthritis patients, the DAS-28 declined at 6 months follow-up without reaching statistical significance [n = 8; 4.8 (2.5-7.5) vs 3.7 (2.6-6.6); p = 0.3]. Of 8, 5patients were RF and/or anti-CCP antibody positive. Similar results were obtained for secondary outcome measures (tender and swollen joint count, VAS, CRP, ESR). Additional positive effects of RTX were seen on SSc-related myopathy (CK levels, 273 + 177 vs 184 + 139; n = 12, P = 0.03) and on digital ulcers [total number per patient 1 (1-3) vs 0 (0-1); n = 23; P = 0.0086]. During RTX treatment 14 patients had infections, 3 serum sickness, 2 allergic reactions and 1 lung fibrosis aggravation, 29 fatigue and 9 nausea. Four patients died, one possibly related to RTX treatment (pneumonia and cardiac failure 1.5 months after RTX infusion). Conclusion. This large EUSTAR cohort study points at positive effects of RTX in particular on skin fibrosis, and suggests randomized controlled trial in SSc patient

Thermal architecture of the ESA ARIEL payload

The Atmospheric Remote-sensing Infrared Exoplanets Large-survey (ARIEL) is a space project selected by the European Space Agency for the Phase A study in the context of the M4 mission within the Cosmic Vision 2015-2025 programme. ARIEL will probe the chemical and physical properties of a large number of known exoplanets by observing spectroscopically their atmosphere, to extend our knowledge of how planetary systems form and evolve. To achieve its scientific objectives, the mission is designed as a dedicated 3.5-years survey for transit and eclipse spectroscopy, with an instrumental layout based on a 1-m class telescope feeding two spectrometer channels that cover the band 1.95 to 7.8 μm and four photometric channels in the visible to near-IR range. The high sensitivity requirements of the mission need an extremely stable thermo-mechanical platform. In this paper we describe the thermal architecture of the payload and discuss the main requirements that drive the design. The ARIEL thermal configuration is based on a passive and active cooling approach. Passive cooling is achieved by a V-Groove based design that exploits the L2 orbit favorable thermal conditions. The telescope and the optical bench are passively cooled to a temperature close to 50K to achieve the required sensitivity and stability. The photometric detectors are maintained at the operating temperature of 50K by a dedicated radiator coupled to cold space. The IR spectroscopic channel detectors require a lower temperature reference. This colder stage is provided by an active cooling system based on a Neon Joule-Thomson cold end, fed by a mechanical compressor, able to reach temperatures lower than 30K. Thermal stability of the telescope and detector units is one of the main drivers of the design. The periodical perturbations due to orbital changes, to the active cooling or to other internal instabilities make the temperature control one of the most critical issues of the whole architecture. The thermal control system design, based on a combination of passive and active solutions aimed at maintaining the required stability at the telescope and detector stages level, is described. We report here about the baseline thermal architecture at the end of the Phase A, together with the main trade-offs needed to enable the ARIEL exciting science in a technically feasible payload design. Thermal modeling results and preliminary performance predictions in terms of steady state and transient behavior are also discussed