Glioblastoma multiforme:Diagnosis, treatment, and invasion

Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.

Clinical prediction scores predicting weaning failure from invasive mechanical ventilation:Role and limitations

Invasive mechanical ventilation(IMV)has become integral to modern-day critical care.Even though critically ill patients frequently require IMV support,weaning from IMV remains an arduous task,with the reported weaning failure(WF)rates being as high as 50%.Optimizing the timing for weaning may aid in reducing time spent on the ventilator,associated adverse effects,patient discomfort,and medical care costs.Since weaning is a complex process and WF is often multifactorial,several weaning scores have been developed to predict WF and aid decision-making.These scores are based on the patient's physiological and ventilatory parameters,but each has limitations.This review highlights the current role and limitations of the various clinical prediction scores available to predict WF.

Comparative Analysis of Population Genetic Structure in Bemisia tabaci(Gennadius) Biotypes B and Q Based on ISSR Marker

Bemisia tabaci （Gennadius） biotypes B and Q are two invasive biotypes in the species complex. The comparison of the population genetic structure of the two biotypes is of significance to show their invasive mechanism and to their control. The intersimple sequence repeats （ISSR） marker was used to analyze the 16 B-biotype populations and 4 Q-biotype populations worldwide with a Trialeurodes vaporariorum population in Shanxi Province, China, and a B. tabaci non-B/Qbiotype population in Zhejiang Province, China, was used as control populations. The analysis of genetic diversity showed that the diversity indexes of biotype Q including Nei＇s gene diversity index, Shannon informative index, and the percentage of polymorphic loci were higher than those of biotype B. The high genetic diversity of biotype Q might provide the genetic basis for the excellent ecological adaptation. Cluster analysis suggested that the ISSR could not be used in the phylogenetic analysis though it could easily distinguish the biotypes of B. tabaci. The difference of the population genetic structure between the biotype B and the biotype Q exists based on the ISSR marker. Meanwhile, the results suggested that the molecular marker has its limitation in the phylogenetic analysis among the biotypes of B. tabaci.

Use of inflammatory markers as predictor for mechanical ventilation in COVID-19 patients with stagesⅢb-Ⅴchronic kidney disease?

BACKGROUND Studies have shown elevated C-reactive protein(CRP)to predict mechanical ventilation(MV)in patients with coronavirus disease 2019(COVID-19).Its utility is unknown in patients with chronic kidney disease(CKD),who have elevated baseline CRP levels due to chronic inflammation and reduced renal clearance.AIM To assess whether an association exists between elevated inflammatory markers and MV rate in patients with stagesⅢb-ⅤCKD and COVID-19.METHODS We conducted a retrospective cohort study on patients with COVID-19 and stagesⅢb-ⅤCKD.The primary outcome was the rate of invasive MV,the rate of noninvasive MV,and the rate of no MV.Statistical analyses used unpaired t-test for continuous variables and chi-square analysis for categorical variables.Cutoffs for variables were CRP:100 mg/L,ferritin:530 ng/mL,D-dimer:0.5 mg/L,and lactate dehydrogenase(LDH):590 U/L.RESULTS 290 were screened,and 118 met the inclusion criteria.CRP,D-dimer,and ferritin were significantly different among the three groups.On univariate analysis for invasive MV(IMV),CRP had an odds ratio(OR)-5.44;ferritin,OR-2.8;LDH,OR-7.7;D-dimer,OR-3.9,(P<0.05).The admission CRP level had an area under curve-receiver operator characteristic(AUROC):0.747 for the IMV group(sensitivity-80.8%,specificity-50%)and 0.663 for the non-IMV(NIMV)group(area under the curve,sensitivity-69.2%,specificity-53%).CONCLUSION Our results demonstrate a positive correlation between CRP,ferritin,and D-dimer levels and MV and NIMV rates in CKD patients.The AUROC demonstrates a good sensitivity for CRP levels in detecting the need for MV in patients with stagesⅢb-ⅤCKD.This may be because of the greater magnitude of increased inflammation due to COVID-19 itself compared with increased inflammation and reduced clearance due to CKD alone.

Respiratory evaluation of patients requiring ventilator support due to acute respiratory failure

This review, based on relevant published evidence and the authors` clinical experience, presents how to evaluate a patient with acute respiratory failure requiring ventilatory support. This patient must be carefully evaluated by nurses, physiotherapists, respiratory care practitioners and physicians regarding the elucidation of the cause of the acute episode of respiratory failure by means of physical examination with the measurement of respiratory parameters and assessment of arterial blood gases analysis to make a correct respiratory diagnosis. After the initial evaluation, the patient must quickly receive adequate oxygen and ventilatory support that has to be carefully monitored until its discontinuation. When available, a noninvasive ventilation trial must be done in patients presenting desaturation during oxygen mask and or PaCO2 retention, especially in cases of cardiogenic pulmonary edema and severe exacerbation of chronic obstructive pulmonary disease. In cases of noninvasive ventilation trial-failure, endotracheal intubation and invasive protective mechanical ventilation must be promptly initiated. In severe ARDS patients, low tidal ventilation, higher PEEP levels, prone positioning and recruitment maneuvers with adequate PEEP titration should be used. Recently, new modes of ventilation should allow a better patient-ventilator interaction or synchrony permitting a sufficient unloading of respiratory muscles and increase patient comfort. Patients with chronic obstructive pulmonary disease may be considered for a trial for early extubation to noninvasive positive pressure ventilation in centers with extensive experience in noninvasive positive pressure ventilation.

Clinical profile of mechanically ventilated COVID-19 patients:A retrospective observational study from Dubai

Background:We did a retrospective analysis of critical coronavirus disease 2019(COVID-19)patients admitted to our intensive care unit(ICU).The objective was to evaluate the outcome,risk factors and effect of prone position in critically ill patients requiring invasive mechanical ventilation(IMV).Patients and methods:The data were collected regarding demographics,comorbidities,laboratory parameters and treatment.Logistic regression was used for analysis of the association of risk factors to the outcome.Results:From 15 March to 30 May 2020,35(59.3%)out of 59 critical COVID-19 requiring IMV were admitted to a tertiary care hospital in Dubai.The day-28 ICU mortality was 28.8% and 48.6% in patients requiring IMV.Prone position(PP)was used in 17(48.6%)patients for median duration of 19(5-20)hours with significant PaO_(2)/FiO_(2) improvement.Acute kidney injury was common(30.5%),and half of the patients required renal replacement therapy(RRT)with higher mortality(77.8%).Lactate dehydrogenase(LDH)odd ratio(OR)-1.006[95%CI-1.00-1.01],D-dimer(OR-1.003[1.000-1.000]),low total leucocyte count(OR-1.135[1.01-1.28]),and lymphopenia(OR-0.909[0.84-0.98])were independently associated with increased risk of IMV.Conclusions:IMV requirement in patients with COVID-19 is associated with higher mortality.Inflammatory markers like LDH,D-dimer,and lymphopenia can be used to predict the prognosis.The patients with COVID-19 on IMV respond significantly with prone position,and it should be considered early with a longer duration.

A novel TRPC6-dependent mechanism of TGF-β-induced migration and invasion of human hepatocellular carcinoma cells

Mechanisms on cancer cell migration and invasion have been major topics of cancer research and anti-cancer therapy development. Among the multiple cell signaling pathways involved in cell migration, those elicited by transforming growth factorβ（TGF-β） have attracted tremendous attention. The TGF-βpolypeptide cytokines include four isoforms：TGF-β1, TGF-β2, TGF-β3, and TGF-β4, which are secreted mainly from cells of white blood cell lineage, such as macrophages, T cells and platelets.

Analysis of risk factors for hospital mortality in patients with chronic obstructive pulmonary diseases requiring invasive mechanical ventilation

Background Accurate prediction for prognosis is important for hospitalized patients with chronic obstructive pulmonary disease （COPD） requiring invasive mechanic ventilation （IMV） and for their family members to make end-of-life decisions. The response to therapy in such a patient population has rarely been investigated. The aim of the study was to evaluate the risk factors in these patients and investigate their response to IMV and the relationship between their responses and prognosis. Methods A cohort of 138 patients with COPD requiring IMV≥12 hours for acute respiratory failure of diverse etiological factors during a 4-year period were retrospectively studied using prospectively gathered data. All variables potentially related to hospital mortality were evaluated by univariate and multiple stepwise logistic regression analysis. Results The mean age of all patients investigated was （65.7±11.6） years and the hospital mortality was 39.9% （31.1% with COPD exacerbation）. Correction of acidosis （pHi〉7.30） was seen in 58 patients （69.9%） in survivors but only 12 patients （21.8%） in nonsurvivors （P〈0.05） after ventilation. Using multivariate logistic analysis, the variables independently associated with hospital mortality were a higher acute physiology score before intubation, lower pH value measured 24 hours after the onset of ventilation and development of multiorgan dysfunction syndrome （MODS）. Conclusions In COPD patients requiring IMV, the postintubation pH value can not only reflect patients＇ response to treatment, but also serve as an independent determinant of hospital mortality apart from other risk factors such as a higher preintubation APACHE II score and development of MODS. A close correlation between the response to IMV and prognosis was proved in these patients.

Effect of noninvasive positive pressure ventilation on weaning success in patients receiving invasive mechanical ventilation： a meta-analysis

Background Noninvasive positive pressure ventilation （NIPPV） has been proposed to shorten the duration of mechanical ventilation in intubated patients, especially those who fail initial weaning from invasive mechanical ventilation （IMV）. However, there are also some discrepancies in terms of weaning success or failure, incidence of re-intubation, complications observed during study and patient outcomes. The primary objective of this update was to specifically investigate the role of NIPPV on facilitating weaning and avoiding re-intubation in patients intubated for different etiologies of acute respiratory failure, by comparing with conventional invasive weaning approach. Methods We searched randomized controlled trials （RCTs） comparing noninvasive weaning of early extubation and immediate application of NIPPV with invasive weaning in intubated patients from PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Knowledge and Springerlink databases. Records from conference proceedings and reference lists of relevant studies were also identified. Results A total of 11 RCTs with 623 patients were available for the present analysis. Compared with IMV, NIPPV significantly increased weaning success rates （odds ratio （OR）： 2.50, 95% confidence interval （C/）： 1.46-4.30, P=0.0009）, decreased mortality （OR： 0.39, 95% CI： 0.20-0.75, P=0.005）, and reduced the incidence of ventilator associated pneumonia （VAP） （OR： 0.17, 95% CI： 0.08-0.37, P 〈0.00001） and complications （OR： 0.22, 95% CI： 0.07-0.72, P=0.01）. However, effect of NIPPV on re-intubation did not reach statistical difference （OR： 0.61, 95% CI： 0.33-1.11, P=0.11）. Conclusions Early extubation and immediate application of NIPPV is superior to conventional invasive weaning approach in increasing weaning success rates, decreasing the risk of mortality and reducing the incidence of VAP and complications, in patients who need weaning from IMV. However, it should be applied with caution, as there is insufficient beneficial evidence to definitely recommend it in terms of avoidinQ re-intubation.

Prognosis and weaning of elderly multiple organ dysfunction syndrome patients with invasive mechanical ventilation

Background Elderly multiple organ dysfunction syndrome （MODS） patients receiving invasive mechanical ventilation have poor prognosis in intensive care units （ICUs）.We studied the usefulness of four commonly used severity scores and extrapulmonary factors that affected weaning to predict outcome of such patients.Methods Clinical data of 197 patients on admission to ICUs （from January 2009 to June 2012） were used retrospectively.The Acute Physiology and Chronic Health Evaluation （APACHE） Ⅱ,APACHE Ⅲ,Sample Acute Physiological Score （SAPS） Ⅱ and MODS scores were calculated.All the patients were grouped into survivors and nonsurvivors according to the prognosis.Patients,who weaned from ventilator （n=154）,were subdivided into a successful weaning group and a failed weaning group.The receiver operating characteristic （ROC） curves and Logistic regression was used for prognostic and weaning assessment.Results Based on the outcomes,the areas under the ROC of APACHE Ⅱ,APACHE Ⅲ,SAPS Ⅱ,and MODS were 0.837,0.833,0.824,and 0.837,respectively.The Logistic regression analysis revealed that the odds ratio （OR） of underlying lung diseases,serum albumin and creatinine,and the number of organ failures was 2.374,0.920,1.003,and 1.547.APACHE Ⅱ scores on admission performed excellent （ROC：0.921） on the weaning assessments.Conclusions APACHE Ⅱ and MODS systems were marginally better for evaluating the prognosis of elderly MODS patients who received invasive mechanical ventilation.Underlying lung diseases,serum albumin,serum creatinine and the number of organ failures were independent prognostic factors.Using the APACHE Ⅱ scores on admission before weaning may increase the likelihood of successful weaning.（ClinicalTrial.gov identifier NCT01802983）.

Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate‑to‑severe bronchopulmonary dysplasia in very preterm infants:a multicentrer prospective study

Objectives We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia(BPD)and focus on discussing its relationship with the duration of initial invasive mechanical ventilation(IMV)in very preterm neonates less than 32 weeks of gestational age(GA).Methods We performed a prospective cohort study involving infants born at 23–31 weeks of GA who were admitted to 47 different neonatal intensive care unit(NICU)hospitals in China from January 2018 to December 2021.Patient data were obtained from the Sina-northern Neonatal Network(SNN)Database.Results We identified 6538 very preterm infants,of whom 49.5%(3236/6538)received initial IMV support,and 12.6%(823/6538)were diagnosed with moderate-to-severe BPD symptoms.The median duration of initial IMV in the moderateto-severe BPD group was 26(17–41)days,while in the no or mild BPD group,it was 6(3–10)days.The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs.Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV[adjusted odds ratio(AOR):1.97;95%confidence interval(CI):1.10–2.67],late-onset neonatal sepsis(LONS),and patent ductus arteriosus(PDA).Conclusion In this multicenter cohort study,the duration of initial IMV was still relatively long in very premature infants,and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.

Effects of clonal integration on allelopathy of invasive plant Wedelia trilobata under heterogeneous light conditions

Plant invasion is one of the most serious threats to ecosystems worldwide.When invasive plants with the ability of clonal growth invading or colonizing in new habitat,their interconnected ramets may suffer from heterogeneous light.Effects of clonal integration on allelopathy of invasive plants are poorly understood under heterogeneous light conditions.To investigate the effects of clonal integration on allelopathy of invasive plant Wedelia trilobata under heterogeneous light conditions,a pot experiment was conducted by using its clonal fragments with two successive ramets.The older ramets were exposed to full light,whereas the younger ones were subjected to 20%full light.The younger ramets of each clonal fragment were adjacently grown with a target plant(one tomato seedling)in a pot.Stolon between two successive ramets was either severed or retained intact.In addition,two tomato seedlings(one as target plant)were adjacently grown in a pot as contrast.Compared with severing stolon,biomass accumulation,foliar chlorophyll and nitrogen contents,chlorophyll fluorescence parameters and net photosynthetic rates of the target plants as well as their root length and activity,were significantly decreased when stolon between interconnected ramets of W.trilobata retained intact.Under heterogeneous light conditions,transportation or sharing of carbohydrate between two successive ramets enhanced allelopathy of the young ramets subjected to 20%full light treatment.It is suggested that clonal integration may be important for invasion or colonization of invasive plants with ability of clonal growth under heterogeneous light conditions.

Non-invasive versus invasive mechanical ventilation for respiratory failure in severe acute respiratory syndrome

Background Severe acute respiratory syndrome is frequently complicated by respiratory failure requiring ventilatory support.We aimed to compare the efficacy of non-invasive ventilation against invasive mechanical ventilation treating respiratory failure in this disease.Methods Retrospective analysis was conducted on all respiratory failure patients identified from the Hong Kong Hospital Authority Severe Acute Respiratory Syndrome Database.Intubation rate,mortality and secondary outcome of a hospital utilizing non-invasive ventilation under standard infection control conditions(NIV Hospita1)were compared against 13 hospitals using solely invasive ventilation(IMV Hospitals).Multiple logistic regression analyses with adjustments for confounding variables were performed to test for association between outcomes and hospital groups.Results Both hospital groups had comparable demographics and clinical profiles,but NIV Hospital(42 patients)had higher lactate dehydrogenase ratio and worse radiographic score on admission and ribavirin-corticosteroid commencement.Compared to IMV Hospitals(451 patients).NIV Hospital had lower adjusted odds ratios for intubation(0.36,95%C10.164-0.791,P=0.011)and death(0.235.95%C10.077-0.716,P=0.O 11),and improved earlier after pulsed steroid rescue.There were no instances of transmission of severe acute respiratory syndrome among health care workers due to the use of non-invasive ventilation.Conclusion Compared to invasive mechanical ventilation,non-invasive ventilation as initial ventilatory support for acute respiratory failure in the presence of severe acute respiratory syndrome appeared to be associated with reduced intubation need and mortality.

Assessment of respiratory support decision and the outcome of invasive mechanical ventilation in severe COVID-19 with ARDS

Background:The coronavirus disease 2019(COVID-19)is an ongoing pandemic.Invasive mechanical ventilation(IMV)is essential for the management of COVID-19 with acute respiratory distress syndrome(ARDS).We aimed to assess the impact of compliance with a respiratory decision support system on the outcomes of patients with COVID-19-associated ARDS who required IMV.Methods:In this retrospective,single-center,case series study,patients with COVID-19-associated ARDS who required IMV at Zhongnan Hospital of Wuhan University,China,from January 8th,2020,to March 24th,2020,with the final follow-up date of April 20th,2020,were included.Demographic,clinical,laboratory,imaging,and management information were collected and analyzed.Compliance with the respiratory support decision system was documented,and its relationship with 28-day mortality was evaluated.Results:The study included 46 COVID-19-associated ARDS patients who required IMV.The median age of the 46 patients was 68.5 years,and 31 were men.The partial pressure of arterial oxygen(PaO_(2))/fraction of inspired oxygen(FiO_(2))ratio at intensive care unit(ICU)admission was 104 mmHg.The median total length of IMV was 12.0(interquartile range[IQR]:6.0–27.3)days,and the median respiratory support decision score was 11.0(IQR:7.8–16.0).To 28 days after ICU admission,18(39.1%)patients died.Survivors had a significantly higher respiratory support decision score than non-survivors(15.0[10.3–17.0]vs.8.5(6.0–10.3),P=0.001).Using receiver operating characteristic(ROC)curve to assess the discrimination of respiratory support decision score to 28-day mortality,the area under the curve(AUC)was 0.796(95%confidence interval[CI]:0.657–0.934,P=0.001)and the cut-offwas 11.5(sensitivity=0.679,specificity=0.889).Patients with a higher score(>11.5)were more likely to survive at 28 days after ICU admission(log-rank test,P<0.001).Conclusions:For severe COVID-19-associated ARDS with IMV,following the respiratory support decision and assessing completion would improve the progress of ventilation.With a decision score of>11.5,the mortality at 28 days after ICU admission showed an obvious decrease.

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19

Background and aim Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for the current pandemic,can have multi-organ impact.Recent studies show that liver injury could be a manifestation of the disease,and that liver disease could also be related to a worse prognosis.Our aim was to compare the characteristics of patients with severe coronavirus disease 2019(COVID-19)due to SARS-CoV-2 who required intubation versus stable hospitalized patients to identify the early biochemical predictive factors of a severe course of COVID-19 and subsequent requirement for intubation,specifically in Mexican.Methods This was an observational case-control study nested in a cohort study.Complete medical records of patients admitted for confirmed COVID-19 at a tertiary level center in Mexico City were reviewed.Clinical and biochemical data were collected,and the characteristics of patients who required invasive mechanical ventilation(IMV)(cases)were compared with stable hospitalized patients without ventilation(controls).Results We evaluated 166 patients with COVID-19 due to SARS-CoV-2 infection;114(68.7%)were men,the mean age was 50.6±13.3 years,and 27(16.3%)required IMV.The comparative analysis between cases and controls showed(respectively)significantly lower blood oxygen saturation(SpO_(2))(73.5±12.0%vs.83.0±6.8%,P<0.0001)and elevated alanine aminotransferase(ALT)(128(14–1123)IU/L vs.33(8–453)IU/L,P=0.003),aspartate aminotransferase(AST)(214(17–1247)vs.44(12–498)IU/L,P=0.001),lactic dehydrogenase(LDH)(764.6±401.9 IU/L vs.461.0±185.6 IU/L,P=0.001),and D-dimer(3463(524–34,227)ng/mL vs.829(152–41,923)ng/mL,P=0.003)concentrations.Patients in the cases group were older(58.6±12.7 years vs.49.1±12.8 years,P=0.001).Multivariate analysis showed that important factors at admission predicting the requirement for IMV during hospitalization for COVID-19 were AST≥250 IU/L(odds ratio(OR)=64.8,95%confidence interval(CI)7.5–560.3,P<0.0001)and D-dimer≥3500 ng/mL(OR=4.1,95%CI 1.2–13.7,P=0.02).Conclusions Our study confirms the importance of monitoring liver enzymes in hospitalized patients with COVID-19;seriously ill patients have significantly elevated AST and D-dimer concentrations,which have prognostic implications in the SARS-CoV-2 disease course.

Oxygenation strategy during acute respiratory failure in immunocompromised patients

Acute respiratory failure(ARF)in immunocompromised patients remains challenging to treat.A large number of case require admission to intensive care unit(ICU)where mortality remains high.Oxygenation without intubation is important in this setting.This review summarizes recent studies assessing oxygenation devices for immunocompromised patients.Previous studies showed that non-invasive ventilation(NIV)has been associated with lower intubation and mortality rates.Indeed,in recent years,the outcomes of immunocompromised patients admitted to the ICU have improved.In the most recent randomized controlled trials,including immunocompromised patients admitted to the ICU with ARF,neither NIV nor high-flow nasal oxygen(HFNO)could reduce the mortality rate.In this setting,other strategies need to be tested to decrease the mortality rate.Early admission strategy and avoiding late failure of oxygenation strategy have been assessed in retrospective studies.However,objective criteria are still lacking to clearly discriminate time to admission or time to intubation.Also,diagnosis strategy may have an impact on intubation or mortality rates.On the other hand,lack of diagnosis has been associated with a higher mortality rate.In conclusion,improving outcomes in immunocompromised patients with ARF may include strategies other than the oxygenation strategy alone.This review discusses other unresolved questions to decrease mortality after ICU admission in such patients.