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BackgroundSevere COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers. This presentation is consistent with cytokine release syndrome in chimeric antigen receptor T cell therapy, for which IL-6 blockade is approved treatment. MethodsWe assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). Findings154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.59 (0.36, 0.95)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. InterpretationIn this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with a decreased likelihood of death despite higher superinfection occurrence. Randomized controlled trials are urgently needed to confirm these findings. KEY POINTSO_ST_ABSQuestionC_ST_ABSCan therapy with the IL-6 receptor antagonist tocilizumab improve outcomes in patients with severe COVID-19 illness requiring mechanical ventilation? FindingsIn this observational, controlled study of 154 patients, receipt of tocilizumab was associated with a 45% reduction in the hazard of death, despite twice the frequency of superinfection (54% vs 26%), both of which were statistically significant findings. MeaningTocilizumab therapy may improve survival in patients with COVID-19 illness requiring mechanical ventilation. These results can inform clinical practice pending the results of randomized clinical trials.
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Objective To investigate the localization,zone and activation intensity of olfactory center in young versus elderly healthy volunteers by functional magnetic resonance imaging (BOLD-fMRI),so as to elucidate the effect of age on olfactory center in healthy population.Methods Thirteen right-handed healthy adult volunteers were recruited and divided into two groups:young group (5 males and 3 females,mean aged 23 years) and elderly group (2 males and 3 females,mean aged 69.2 years).The olfactory stimulus was r-undecalactone,and it was given according to a block design.The fMRI detection was performed on Philips Achieva 3.0 T MR scanner,and data of BOLE-fMRI was processed and analyzed to get cerebration image by using SPM2.Results In groupaveraged maps,both young and elderly group showed significant olfactory activation in right parahippocampal gyrus,left hippocampal sulcus,right and left superior temporal gyrus,etc,subcortical activation in right thalamus,dorsal pons,and cerebellum activation in cerebellar vermis.Activations in right inferior frontal gyrus,right middle frontal gyrus,right medial occipito-temporal gyrus and right fimbria of hippocampus were observed only in young group,while activation in bilateral middle temporal gyrus was observed only in elderly group.Activation area was apparently smaller and activation degree was lower in elderly group than in young group.Activation intensity in right superior parietal lobule and bilateral superior temporal gyri was higher in male group than in female group (t=13.7,6.08,5.36,respectively,all P＜0.001).Conclusions The intensity of activation in olfactory center is lower in the elderly than in the young,and absence of part of the active regions is found in the elderly,which demonstrates the regression of olfactory center in the elderly.The olfactory center shows right-predominant activation,and olfactory activation intensity in some cortical regions is higher in males than in females.
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Objective To investigate the clinical efficacy of new-type patent endotracheal tube in difficult endotrachea intubation patients.Methods Seventy-three patients with the abnormal airways were selected as our subjects.Patients were given the traditional endotracheal tube by mouth after anesthesia.The successes patients in terms of endotracheal intubation were as group Ⅰ (n =73).The failed patients were asgroup Ⅱ (n =63),who performed the secondary endotracheal intubation with new type patent endotracheal tube.Analyze the success rate of intubation of the two groups when on use the tube core.Results The first time intubation success rate and intubation success rate was (2.7％ (2/73),13.7％ (10/73) respectively) in Ⅰ group,and 73.02％ (46/63) and 98.41％ (62/63) respectively in the group Ⅱ,and there was the significant difference between two groups (x2 =36.01,31.08 respectively,P ＜ 0.01).Conclusion The new type endotracheal tube was proved with three advamage of good plasticity,without need of auxiliary core intubation with trachealtube and give full play to lead the soft cannula guide tubes leading role.Therefore,the new type patent endotracheal tube has more efficacy over traditional tube.
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The somatostatin analogue pasireotide is a new type of protein which is the first therapeutic agent targeted to the pituitary.Pasireotide can prevent adrenocorticotropic hormone release and inhibit the growth of tumor cells after coupling with somatostatin receptor of the target cell membranes.Pasireotide has a high binding affinity for most of somatostatin receptor (SSTR) subtypes and in particular for SSTR5.Pasireotide can paly an important role in the new round of new targets for individualized diagnosis and treatment of tumors through the studies of translational medicine.
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Single nucleotide polymorphisms (SNPs) are genetic variations that determine the differences between any two unrelated individuals. Various population groups can be distinguished from each other using SNPs. For instance, the HapMap dataset has four population groups with about ten million SNPs. For more insights on human evolution, ethnic variation, and population assignment, we propose to find out which SNPs are significant in determining the population groups and then to classify different populations using these relevant SNPs as input features. In this study, we developed a modified t-test ranking measure and applied it to the HapMap genotype data. Firstly, we rank all SNPs in comparison with other feature importance measures including F-statistics and the informativeness for assignment. Secondly, we select different numbers of the most highly ranked SNPs as the input to a classifier, such as the support vector machine, so as to find the best feature subset corresponding to the best classification accuracy. Experimental results showed that the proposed method is very effective in finding SNPs that are significant in determining the population groups, with reduced computational burden and better classification accuracy.
