ObjectiveThe aim of this systematic review was to assess the diaphragmatic dysfunction (DD) as a predictor of weaning outcome.BackgroundSuccessful weaning depends on several factors: muscle strength, cardiac, respiratory and metabolic. Acquired weakness in mechanical ventilation is a growing important cause of weaning failure. With the development of ultrasonography, DD can be evaluated with ultrasound in weakness patients to predict weaning outcomes.MethodsThe Cochrane Library, PubMed, Embase, Ovid Medline, WanFang Data and CNKI were systematically searched from the inception to September 2017. Ultrasound assessment of DD in adult mechanical ventilation patients was included. Two independent investigators assessed study quality in accordance with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcome was diaphragmatic thickness and excursion in the weaning success and failure group. The secondary outcome was the influence of DD on weaning outcome.ResultsEleven studies involving a total of 436 patients were included. There were eight studies comparing diaphragmatic excursion (DE), five comparing the diaphragmatic thickening fraction (DTF) and two comparing DD between groups with and without successful weaning. Overall, the DE or DTF had a pooled sensitivity of 0.85 (95% CI 0.77 to 0.91) and a pooled specificity of 0.74 (95% CI 0.66 to 0.80) for predicting weaning success. There was high heterogeneity among the included studies (I2=80%; p=0.0006). The rate of weaning failure was significantly increased in patients with DD (OR 8.82; 95% CI 3.51 to 22.13; p<0.00001).ConclusionsBoth DE and DTF showed good diagnostic performance to predict weaning outcomes in spite of limitations included high heterogeneity among the studies. DD was found to be a predictor of weaning failure in critically ill patients.

Background Position intervention has been shown to improve oxygenation, but its role in non-invasively ventilated severe COVID-19 patients has never been assessed. The objective of this study was to investigate the efficacy of early position intervention on non-invasively ventilated severe COVID-19 patients. Methods This was a single-center, prospective observational study in consecutive severe COVID-19 patients managed in a provisional ICU at Renmin Hospital of Wuhan University during January 31st to February 15th, 2020. Patients with chest CT showing exudation or consolidation in bilateral peripheral and posterior part of the lungs were included. Early position intervention (prone or lateral) was commenced for &gt; 4 hours daily for 10 days, while others had standard care. Results The baseline parameters were comparable between position intervention group (n = 17) and standard care group (n = 35). Position intervention was well-tolerated and increased cumulative adjusted mean difference of SpO2/FiO2 (409, 95% CI 86 to 733) and ROX index (26, 95% CI 9 to 43) with decreased Borg scale (−9, 95 CI −15 to −3) during first 7 days. It also facilitated absorption of lung lesions and reduced patients of high National Early Warning Score 2 (≥ 7) on days 7 and 14 with a trend toward fastened clinical improvement. Virus shedding and length of hospital stay were comparable between the two groups. Conclusions This study provides the first evidence for improved oxygenation and lung lesion absorption using early position intervention in non-invasively ventilated severe COVID-19 patients and warrants further randomized trials.

Objective: The aims of this systematic review and meta-analysis were to summarize the current existing evidence on the outcome of critically ill patients with COVID-19 as well as to evaluate the effectiveness of clinical interventions.Data Sources: We searched MEDLINE, the Cochrane library, Web of Science, the China Biology Medicine disc, China National Knowledge Infrastructure, and Wanfang Data from their inception to May 15, 2021. The search strings consisted of various search terms related to the concepts of mortality of critically ill patients and clinical interventions.Study Selection: After eliminating duplicates, two reviewers independently screened all titles and abstracts first, and then the full texts of potentially relevant articles were reviewed to identify cohort studies and case series that focus on the mortality of critically ill patients and clinical interventions.Main Outcomes and Measures: The primary outcome was the mortality of critically ill patients with COVID-19. The secondary outcomes included all sorts of supportive care.Results: There were 27 cohort studies and six case series involving 42,219 participants that met our inclusion criteria. All-cause mortality in the intensive care unit (ICU) was 35% and mortality in hospital was 32% in critically ill patients with COVID-19 for the year 2020, with very high between-study heterogeneity (I2 = 97%; p &lt; 0.01). In a subgroup analysis, the mortality during ICU hospitalization in China was 39%, in Asia—except for China—it was 48%, in Europe it was 34%, in America it was 15%, and in the Middle East it was 39%. Non-surviving patients who had an older age [−8.10, 95% CI (−9.31 to −6.90)], a higher APACHE II score [−4.90, 95% CI (−6.54 to −3.27)], a higher SOFA score [−2.27, 95% CI (−2.95 to −1.59)], and a lower PaO2/FiO2 ratio [34.77, 95% CI (14.68 to 54.85)] than those who survived. Among clinical interventions, invasive mechanical ventilation [risk ratio (RR) 0.49, 95% CI (0.39–0.61)], kidney replacement therapy [RR 0.34, 95% CI (0.26–0.43)], and vasopressor [RR 0.54, 95% CI (0.34–0.88)] were used more in surviving patients.Conclusions: Mortality was high in critically ill patients with COVID-19 based on low-quality evidence and regional difference that existed. The early identification of critical characteristics and the use of support care help to indicate the outcome of critically ill patients.

Median survival of pancreatic ductal adenocarcinoma cancer (PDAC) is 6 months, with 9% 5year survival. Standard-of-care gemcitabine (Gem) provides only modest survival benefit, and combination therapies integrating novel targeted agents could improve outcomes. FGF receptors (FGFR) play important roles in PDAC growth and invasion. Therefore, FGFR inhibitors (FGFRi) merit further investigation. Efficacy of Gem combined with BGJ398, a pan-FGFRi, was investigated in multiple PDAC cell lines exposed to the drugs alone and combined. Cell cycle distribution and cell numbers were quantified over time. Two pharmacodynamic models were developed to investigate Gem/BGJ398 interactions quantitatively: a drug-mediated cell proliferation/death model, and a drug-perturbed cell cycle progression model. The models captured temporal changes in cell numbers, cell cycle progression, and cell death during drug exposure. Simultaneous fitting of all data provided reasonable parameter estimates. Therapeutic efficacy was then evaluated in a PDAC mouse model. Compared to Gem alone, combined Gem+FGFRi significantly down-regulated ribonucleotide-diphosphate reductase large subunit (RRM1), a Gem resistance (GemR) biomarker, suggesting the FGFRi inhibited GemR emergence. The cell proliferation/death pharmacodynamic model estimated the drug interaction coefficient ψ death =0.798, suggesting synergistic effects. The mechanism-based cell cycle progression model estimated drug interaction coefficient ψ cycle =0.647, also suggesting synergy. Thus FGFR inhibition appears to synergize with Gem in PDAC cells and tumors by sensitizing cells to Gem-mediated inhibition of proliferation and cell cycle progression.