A phase II study of induction chemotherapy followed by concurrent chemoradiotherapy in elderly patients with locally advanced non-small-cell lung cancer.

The optimal management of unresectable locally advanced non-small-cell lung cancer in older patients has not been defined to date. The present phase II study was planned to evaluate the activity and safety of platinum-based induction chemotherapy followed by concurrent chemoradiotherapy in elderly patients with locally advanced non-small-cell lung cancer. Patients received two cycles of paclitaxel (175 mg/m) and carboplatin (area under the curve: 5) day 1, every 3 weeks. Chemoradiotherapy (thoracic radiation therapy) was initiated on day 42 and consisted of 1.8 Gy daily, five times per week over 5 weeks (45.0 Gy target dose) followed by 10 2.0 Gy daily fractions. Concomitant chemotherapy was weekly paclitaxel 50 mg/mq followed by weekly carboplatin at an area under the curve of 2. The eligibility for patients: age 70 or older and histologically documented untreated non-small-cell lung cancer, locally advanced, unresectable, stage III A N2 bulky or III B. Thirty consecutive patients were enrolled onto the study. The median age was 73 (range 70-76). According to the intention-to-treat analysis, 1 month after the end of combined chemoradiotherapy, we observed complete and partial responses in one and 19 of the 30 patients, respectively, for an overall response rate of 66% (95% confidence interval, 45-76%). Median progression-free survival was 8.7 months (95% confidence interval, 3.4-37.8) and median survival was 15 months (95% confidence interval, 4.2-52.1). During the treatment, 12 patients (40.0%) experienced grade 3-4 neutropenia, two patients neutropenic fever, and three patients grade 3 anaemia and grade 3 thrombocytopenia, respectively. Grade 3 oesophagitis, during concomitant radiotherapy, was observed in six patients (20.0%). No treatment-related mortality was reported. The investigated sequential approach including induction chemotherapy followed by concurrent chemoradiotherapy appears safe and seems a reasonable chance for the treatment of locally advanced non-small-cell lung cancer in the elderly population

Finitely generated free Heyting algebras via Birkhoff duality and coalgebra

Algebras axiomatized entirely by rank 1 axioms are algebras for a functor and thus the free algebras can be obtained by a direct limit process. Dually, the final coalgebras can be obtained by an inverse limit process. In order to explore the limits of this method we look at Heyting algebras which have mixed rank 0-1 axiomatizations. We will see that Heyting algebras are special in that they are almost rank 1 axiomatized and can be handled by a slight variant of the rank 1 coalgebraic methods

Molecular velocity auto-correlation of simple liquids observed by NMR MGSE method

The velocity auto-correlation spectra of simple liquids obtained by the NMR method of modulated gradient spin echo show features in the low frequency range up to a few kHz, which can be explained reasonably well by a $t^{-3/2}$ long time tail decay only for non-polar liquid toluene, while the spectra of polar liquids, such as ethanol, water and glycerol, are more congruent with the model of diffusion of particles temporarily trapped in potential wells created by their neighbors. As the method provides the spectrum averaged over ensemble of particle trajectories, the initial non-exponential decay of spin echoes is attributed to a spatial heterogeneity of molecular motion in a bulk of liquid, reflected in distribution of the echo decays for short trajectories. While at longer time intervals, and thus with longer trajectories, heterogeneity is averaged out, giving rise to a spectrum which is explained as a combination of molecular self-diffusion and eddy diffusion within the vortexes of hydrodynamic fluctuations.Comment: 8 pages, 6 figur

Test for CCR5 tropism and treatment with maraviroc in Sicily: an observational retrospective multicentre study

Purpose of the study: Maraviroc (MVC) is the first CCR5 inhibitor licensed for clinical use. A pre-treatment test is mandatory to identify R5 tropic patients. Aim of this study is to detect indications and results of tropism test and to evaluate efficacy and tolerability of MVC-based regimen. Methods: An observational retrospective multicentre study was performed in Sicily in 15 Infectious Diseases Units. Clinical records of 213 screened for tropism HIV+ subjects were reviewed for age, sex, risk, clinical stage (CDC, CD4 cell count, HIV RNA viral load), therapeutic line, indication and result of test for tropism; within subjects treated with MVC, HIV RNA, CD4 cell count and metabolic parameters trend and adverse events were analysed. Summary of results: Median age 44 (IQR 30–50) years, 67.1% males; 46.3% heterosexuals, 28.6% MSMs, 21.4% IVDUs; 23.7% CDC A, 32.1% CDC B, 44.2% CDC C; median CD4 was 217 (IQR 121–374) cells/µl and mean of HIV RNA was 4.72 (Cl 95% 4.07–4.67) log10 copies/ml; median therapeutic line was 4 (IQR 2–7). 80.8% were submitted to Trofile™ test, 19.2% to genotypic test, 75.5% after a therapeutic failure. 56.8% of subjects screened were R5, 7.5% X4, 21.6% DM, 14% undefined. All X4 patients were tested after a therapeutic failure; patients screened for toxicity were more frequently R5 (75%) (p<0.01). 76 (35.7%) multi-experienced (at baseline 8% HIV RNA<50 copies/ml, median CD4 cell count 219 (IQR 124–345) cells/µl) subjects were treated with MVC plus an optimized background treatment: MVC was associated in 74% of cases with a protease inhibitors (56% darunavir/ritonavir), in 42% with raltegravir, in 56% with a NUC-sparing regimen. After 12 months of treatment 56.8% (ITT analysis) and 61.7% (AT) of patients had HIV RNA<50 copies/ml; median CD4 cell count was 387 (IQR 222–455) cells/µl. After 24 months 64.8% (ITT) 80% (AT) had HIV-RNA<50 copies/ml. Median CD4 cell count was 381 (IQR 218.515) cells/µl with a median increase of 168 (IQR 54–274) cells/µl. At 24 months median value of total and HDL cholesterol and triglycerides were within the normal range. 7 patients stopped the treatment: 2 died, 1 adverse event, 4 virological failure. Conclusions: Although the test has been proposed to patients with long treatment history and failure, only 3/5 of R5 tropic patients were treated with MVC. An high number of multi-experienced subjects treated with a MVC-based regimen obtained HIV RNA<50 copies/ml and a satisfactory increase of CD4 cell count

The PROVENT-C19 registry: A study protocol for international multicenter SIAARTI registry on the use of prone positioning in mechanically ventilated patients with COVID-19 ARDS

Background The worldwide use of prone position (PP) for invasively ventilated patients with COVID-19 is progressively increasing from the first pandemic wave in everyday clinical practice. Among the suggested treatments for the management of ARDS patients, PP was recommended in the Surviving Sepsis Campaign COVID-19 guidelines as an adjuvant therapy for improving ventilation. In patients with severe classical ARDS, some authors reported that early application of prolonged PP sessions significantly decreases 28-day and 90-day mortality. Methods and analysis Since January 2021, the COVID19 Veneto ICU Network research group has developed and implemented nationally and internationally the "PROVENT-C19 Registry", endorsed by the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care. . .'(SIAARTI). The PROVENT-C19 Registry wishes to describe 1. The real clinical practice on the use of PP in COVID-19 patients during the pandemic at a National and International level; and 2. Potential baseline and clinical characteristics that identify subpopulations of invasively ventilated patients with COVID-19 that may improve daily from PP therapy. This web-based registry will provide relevant information on how the database research tools may improve our daily clinical practice. Conclusions This multicenter, prospective registry is the first to identify and characterize the role of PP on clinical outcome in COVID-19 patients. In recent years, data emerging from large registries have been increasingly used to provide real-world evidence on the effectiveness, quality, and safety of a clinical intervention. Indeed observation-based registries could be effective tools aimed at identifying specific clusters of patients within a large study population with widely heterogeneous clinical characteristics. Copyright

Utilization of mechanical power and associations with clinical outcomes in brain injured patients. a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

BackgroundThere is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes.MethodsIn this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale <= 12 before intubation) who required mechanical ventilation (MV) >= 24 h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS).ResultsWe included 1217 patients (mean age 51.2 years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9 J/min [IQR 9.2-15.1], 13 J/min [IQR 10-17], and 14 J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9 J/min, aRR at 17 J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22).ConclusionsExposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation

The instrument suite of the European Spallation Source

An overview is provided of the 15 neutron beam instruments making up the initial instrument suite of the European Spallation Source (ESS), and being made available to the neutron user community. The ESS neutron source consists of a high-power accelerator and target station, providing a unique long-pulse time structure of slow neutrons. The design considerations behind the time structure, moderator geometry and instrument layout are presented. The 15-instrument suite consists of two small-angle instruments, two reflectometers, an imaging beamline, two single-crystal diffractometers; one for macromolecular crystallography and one for magnetism, two powder diffractometers, and an engineering diffractometer, as well as an array of five inelastic instruments comprising two chopper spectrometers, an inverse-geometry single-crystal excitations spectrometer, an instrument for vibrational spectroscopy and a high-resolution backscattering spectrometer. The conceptual design, performance and scientific drivers of each of these instruments are described. All of the instruments are designed to provide breakthrough new scientific capability, not currently available at existing facilities, building on the inherent strengths of the ESS long-pulse neutron source of high flux, flexible resolution and large bandwidth. Each of them is predicted to provide world-leading performance at an accelerator power of 2 MW. This technical capability translates into a very broad range of scientific capabilities. The composition of the instrument suite has been chosen to maximise the breadth and depth of the scientific impact o