High-pressure intrapleural chemotherapy: feasibility in the pig model.

International audienceABSTRACT: BACKGROUND: The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. METHODS: Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. RESULTS: The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. CONCLUSIONS: High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Is there variation between hospitals within each region in postoperative mortality for lung cancer surgery in France? A nationwide study from 2013 to 2020

IntroductionThe practice of thoracic surgery for lung cancer is subject to authorization in France. We evaluated the performance of hospitals using 30-day post-operative mortality as a quality indicator, estimating its distribution within each region and measuring its variability between regions.Material and methodsAll data for patients who underwent pulmonary resection for lung cancer in France (2013–2020) were collected from the national hospital administrative database. Thirty-day mortality was defined as any patient who died in hospital (including transferred patients) within the first 30 days after the operation and those who died later during the initial hospitalization. The Standardized Mortality ratio (SMR) was the smoothed, adjusted, hospital-specific mortality rate divided by the expected mortality. To describe the variation in hospital mortality between hospitals in each region, we used different commonly used indicators of variation such as coefficients of variation (CV), interquartile interval or range (IQR), extreme ratio, and systematic component of variance (SCV).ResultsIn 2013–2020, 87,232 patients underwent lung resection for cancer in France. The number of deaths was 2,537, a rate of 2.91%. The median SMR of 199 hospitals was 0.99 with an IQR of 0.86 to 1.18 and a CV of 0.25. Among the regions that had the most hospitals performing lung resections for cancer, the extreme ratio was &amp;gt;2, which means that the maximum value is twice as high as the minimum value. The SCV between hospitals was &amp;gt;10 for two of these regions, which is considered indicative of very high variation. For the other regions (with few hospitals performing lung resections for cancer), the variation between hospitals was lower. Globally, the variability between regions concerning the SMR was moderate, 6% of the variance was due to differences across regions. On the contrary, the hospital volume was significantly related to the SMR (p = 0.003) with a negative linear trend, whatever the region.ConclusionThis work shows significant differences in the practices of the various hospitals within regions. However, overall, the variability in the 30-day mortality rate between regions was moderate. Our findings raises questions regarding the regionalization of major surgical procedures in France.</jats:sec

Diffusion of Minimally Invasive Approach for Lung Cancer Surgery in France: A Nationwide, Population-Based Retrospective Cohort Study

International audienceBackground. The minimally invasive approach (MIA) has gained popularity thanks to its efficacy and safety. Our work consisted of evaluating the diffusion of the MIA in hospitals and the variability of this approach (within and between regions). Methods. All patients who underwent limited resection or lobectomy for lung cancer in France were included from the national hospital administrative database (2013–2020). We described between-hospital differences in the MIA rate over four periods (2013–2014, 2015–2016, 2017–2018, and 2019–2020). The potential influence of the hospital volume, hospital type, and period on the adjusted MIA rate was estimated by a multilevel linear regression. Results. From 2013 to 2020, 77,965 patients underwent a lobectomy or limited resection for lung cancer. The rate of the MIA increased significantly over the four periods (50% in 2019–2020). Variability decreased over time in 7/12 regions. The variables included in the multilevel model were significantly related to the adjusted rate of the MIA. Variability between regions was considerable since 18% of the variance was due to systematic differences between regions. Conclusions. We confirm that the MIA is part of the surgical techniques used on a daily basis for the treatment of lung cancer. However, this technology is mostly used by surgeons in high volume institutions