The recently diagnosed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in December 2019 commonly affects the respiratory system. The ...incidence of acute hypoxic respiratory failure varied among epidemiological studies with high percentage of patients requiring mechanical ventilation with a high mortality. Noninvasive ventilation is an alternative tool for ventilatory support instead of invasive mechanical ventilation, especially with scarce resources and intensive care beds. Initially, there were concerns by the national societies regarding utilization of noninvasive ventilation in acute respiratory failure. Recent publications reflect the gained experience with the safe utilization of noninvasive mechanical ventilation. Noninvasive ventilation has beneficiary role in treatment of acute hypoxic respiratory failure with proper indications, setting, monitoring, and timely escalation of therapy. Patients should be monitored frequently for signs of improvement or deterioration in the clinical status. Awareness of indications, contraindications, and parameters reflecting either success or failure of noninvasive ventilation in the management of acute respiratory failure secondary to COVID-19 is essential for improvement of outcomes.
The
POLD4
gene encodes a subunit (δ4) of DNA polymerase delta, which is a key enzyme involved in DNA replication and repair. Recent studies have suggested that
POLD4
plays a crucial role in ...developing certain cancers. However, there is a lack of knowledge regarding the role of
POLD4
in the context of glioblastoma (GBM). Therefore, in this study we have used various cancer bioinformatics tools to explore the role of
POLD4
in glioblastoma. Data from various sources were accessed to analyze
POLD4
gene expression and estimate tumor-infiltrating immune cells in glioblastoma. Methylation data were retrieved using the MEXPRESS web browser and analyzed. UALCAN webserver was used to analyze the protein expression of
POLD4
. Gene correlation and pathway enrichment analysis were performed using cBioPortal and GSEA software, respectively. Afterward, survival analysis was performed.
POLD4
was significantly upregulated in glioblastoma at both gene and protein levels in GBM, and ROC curve analysis revealed it as a potential biomarker in glioblastoma. GSEA analysis of TCGA-GBM pan-cancer study exhibited that
POLD4
expression was associated with critical pathways, such as interferon-gamma response, G2M checkpoint, inflammatory response, E2F targets, EMT transition, and KRAS signaling pathways. Furthermore,
POLD4
expression was positively correlated with DNA methylation at 3 CpG sites, including Cg16509978, with a Pearson correlation coefficient value of 0.398 (
p
-value ≤ 0.01), while the promoter region had a positive correlation but was not significant. In addition,
POLD4
is significantly linked with poor OS, PFS, and DFS. We also found association of
POLD4
expression with altered immune cell infiltration. In conclusion,
POLD4
is significantly upregulated in glioblastoma and may be used as a potential diagnostic or prognostic biomarker for GBM patients. However, to establish the same a large cohort study is needed.
Graphical Abstract
Using TCGA data and various cancer bioinformatics tools mentioned above we observed very high level of gene and protein expression of
POLD4
in glioblastoma patients. The expression of
POLD4
was significantly correlated with inflammatory and oncogenic pathways and it also has a significant correlation with adverse outcome in patients with glioblastoma.
The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab ...has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.
Existing literature lacks high-quality evidence regarding the ideal intraoperative positive end-expiratory pressure (PEEP) to minimize postoperative pulmonary complications (PPCs). We hypothesized ...that applying individualized PEEP derived from electrical impedance tomography (EIT) would reduce the severity of postoperative lung aeration loss, deterioration in oxygenation, and PPC incidence.
A pilot feasibility study was conducted on 36 patients who underwent open abdominal oncologic surgery. The patients were randomized to receive individualized PEEP or conventional PEEP at 4 cm H2O. The primary outcome was the impact of individualized PEEP on changes in the modified lung ultrasound score (MLUS) derived from preoperative and postoperative lung ultrasonography. A higher MLUS indicated greater lung aeration loss. The secondary outcomes were the PaO2/FIO2 ratio and PPC incidence.
A significant increase in the postoperative MLUS (12 ± 3.6 vs 7.9 ± 2.1, P < 0.001) and a significant difference between the postoperative and preoperative MLUS values (7.0 ± 3.3 vs 3.0 ± 1.6, P < 0.001) were found in the conventional PEEP group, indicating increased lung aeration loss. In the conventional PEEP group, the intraoperative PaO2/FIO2 ratios were significantly lower but not the postoperative ratios. The PPC incidence was not significantly different between the groups. Post-hoc analysis showed the increase in lung aeration loss and deterioration of intraoperative oxygenation correlated with the deviation from the individualized PEEP.
Individualized PEEP appears to protect against lung aeration loss and intraoperative oxygenation deterioration. The advantage was greater in patients whose individualized PEEP deviated more from the conventional PEEP.
Dear Editor,
We have been using sedation for a long time in intensive care units for patients on mechanical ventilation. Sedation aims at facilitating the patient’s ability to remain comfortably ...connected to the ventilator and minimize oxygen consumption. The strategies for sedation vary from deep sedation and light sedation to nosedation. For the last two decades, light sedation with daily interruption is being practiced by most ICUs...
The coronavirus disease 2019 (COVID-19) has affected different countries in a differential manner. The host susceptibility and host factors are important parameters for this variability. This study ...aimed to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19. Available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 168 countries as of 19th September 2021was collected. Countries were divided into four cohorts based upon annual TB incidence and BCG coverage and COVID-19 incidence and case fatality rates were compared using the Kruskal-Wallis test. Countries with low TB incidence and low BCG coverage had the highest COVID-19 incidence per lac population. However, no significant difference was seen in COVID-19 cases fatality rate. Higher TB incidence and BCG coverage were associated with lesser incidence of COVID-19. This result paves the way for research into pathogenesis and host immune response in COVID-19.
Coronavirus disease-2019 (COVID-19) may lead to hypoxemia, requiring intensive care in many patients. Awake prone positioning (PP) is reported to improve oxygenation and is a relatively safe ...modality. We performed a systematic review of the literature to evaluate the available evidence and performed meta-analysis of the effect of awake PP in non-intubated patients on improvement in oxygenation and reducing the need for intubation. We searched the PubMed and EMBASE databases to identify studies using awake PP as a therapeutic strategy in the management of COVID-19. Studies were included if they reported respiratory outcomes and included five or more subjects. The quality of individual studies was assessed by the Qualsyst tool. A meta-analysis was performed to estimate the proportion of patients requiring intubation. The degree of improvement in oxygenation parameters (PaO2: FiO2 or PaO2 or SpO2) was also calculated. Sixteen studies (seven prospective trials, three before-after studies, six retrospective series) were selected for review. The pooled proportion of patients who required mechanical ventilation was 0.25 (95% confidence interval (CI) 0.16-0.34). There was a significant improvement in PaO2: FiO2 ratio, PaO2, and SpO2 during awake PP. To conclude, there is limited evidence to support the efficacy of awake PP for the management of hypoxemia in COVID-19. Further RCTs are required to study the impact of awake PP on key parameters like avoidance of mechanical ventilation, length of stay, and mortality.
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