Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.     

The Impact of Interleukin (IL)-33 Gene Polymorphisms and Environmental Factors on Risk of Asthma in the Iranian Population

Background

Airway epithelial cells secrete Interleukin-33 in response to the different allergens. Several single nucleotide polymorphisms (SNP) of this cytokine have been reported to be involved in the development of asthma. We conducted this study to evaluate the impact of the two most common SNPs of the IL-33 gene (rs1342326 and rs3939286) and environmental factors on the susceptibility to asthma in the Iranian population.

Subjects and Methods

In this study, we enrolled 126 asthmatics patients and 300 age, sex-matched controls. Genotyping was performed by real-time PCR using the TaqMan SNP genotyping assay. Moreover, total serum IgE level, eosinophil count, and skin prick test were accomplished and complete history was taken from all the participants.

Results

The frequencies of mutant genotypes in both SNPs were significantly higher in asthmatics than controls. C/C genotype of rs1342326 [OR (95% CI) 2.50 (1.33–4.69)] and A/A genotype of rs3939286 [OR (95% CI) 2.18 (1.05–4.52)] were associated with higher risk of asthma development. While A/C+C/C genotype of rs1342326 was more prevalent in mild asthma [OR (95% CI) 2.36 (1.14–4.89)], G/A+A/A genotype of rs3939286 was associated with increased risk of moderate and severe asthma [OR (95% CI) 2.53 (1.30–4.94)].

Conclusion

This study revealed that both IL-33 SNPs were associated with an increased risk of asthma. The rs1342326 was associated with atopic, mild and adult-onset asthma and a higher level of eosinophils in peripheral blood. However, rs3939286 was more frequent in moderate and severe asthma. Moreover, rs3939286 was associated with non-atopic and childhood-onset asthma.

     

An 11-year retrospective study on the epidemiology of paediatric burns in the north of Iran

Burn injuries in children are distressing physical and emotional events with long-term disability. However, there is little research on the epidemiology of paediatric burns. This information is essential for the development of prevention intervention and acute management. This study aimed to describe epidemiologic characteristics and clinical outcomes of paediatric burns in a burn center in the north of Iran. A retrospective, single-center study was conducted of children (<18 years) admitted to the burns center between 2011 and 2021. The data were analysed by SPSS 24.0 software. The chi-squared test and Fisher's exact test were used to assess categorical variables, and Student's t-tests or One-Way ANOVA was used to evaluate continuous variables. 2951 paediatric burns with mean age 5.30 ± 5.27 years, were admitted during the 11 years, with 1777 boys (60.2%) and 1174 girls (39.8%). By age groups, the majority of children (59.7%) were between 0 and 4 years old, followed by 5 to 8 years (15.7%), 13 to 18 years (14.6%), and 9 to 12 years (10.0%), respectively. The most cause of injury was Hot liquids & vapours (1604, 54.4%). The mean age for burns with fire & flames, hot liquids & vapours, contact, chemical, and electrical was 4.46 ± 4.84, 5.70 ± 5.39, 5.44 ± 5.42, 3.93 ± 3.86, and 3.53 ± 4.06 years, respectively. The total body surface area (TBSA) burned was 14.96 ± 11.94. The longest length of stay (LOS) related to fire and flame was 5.63 ± 7.57 days. The mortality rate was 1.56%. There were significant differences among aetiology groups for the cost per % TBSA (F = 15.784, P < 0.001), which correlated with the burn depth, TBSA, aetiology, LOS, and age. The Ministry of Health should establish strategies for burn prevention and incorporate data surveillance for burn injuries. Community education on kitchen and cooking safety could positively impact the prevalence and outcomes of paediatric burns.     

Thoracic involvement in Erdheim-Chester disease: computed tomography imaging findings and their association with the <Emphasis Type="Italic">BRAF</Emphasis><Superscript>V600E</Superscript> mutation

Objectives

To investigate the computed tomography (CT) thoracic findings in Erdheim-Chester disease (ECD) and evaluate the association of these findings with the BRAF^V600E mutation.

Methods

This was a prospective study of patients with ECD (n=61, men=46) who underwent thoracic CT imaging. CT examinations were independently interpreted by two experienced radiologists. Association of imaging findings with BRAF^V600E was achieved via the Chi-square or Fisher’s exact test and odds ratios (OR) with 95% confidence intervals (CI), as appropriate.

Results

Fifty-five ECD patients (90%) showed pulmonary findings, which included interlobular septal thickening (69%), pulmonary nodules (62%), airway thickening (13%) and ground glass opacities (36%). Pulmonary nodules were classified by the pattern of distribution: subpleural regions (36%), lung parenchyma (13%) and both regions (13%). Pleural and mediastinal involvement were present in 15% and 62% of cases, respectively. The most common mediastinal finding was sheathing of the right coronary artery (34%), followed by sheathing of the thoracic aorta (30%). The BRAF^V600E mutation, positive in 31 patients, was associated with the frequency of sheathing of the coronary arteries (p = 0.01).

Conclusions

Of the thoracic findings reported in this study, we found a statistically significant positive association between the BRAF^V600E mutation and presence of coronary artery sheathing.

Key Points

? To assess the degree of thoracic involvement in ECD with CT. ? BRAF ^V600E mutation has a high association with right coronary artery sheathing. ? BRAF ^V600E genetic testing detects patients at high risk of developing RCA sheathing.

     

The effect of plantain syrup on heavy menstrual bleeding: A randomized triple blind clinical trial

Given the importance of heavy menstrual bleeding (HMB), we investigated the effect of plantain syrup on HMB. This randomized clinical trial was performed on 68 women with HMB who were referred to the traditional medicine clinics of Mashhad University of Medical Sciences. The intervention group received placebo capsule and plantain syrup, whereas the control group received mefenamic acid capsule and placebo syrup in the first 5 days of menstruation for three menstruation cycles. Patients were asked to complete pictorial blood assessment chart one cycle before the intervention and three intervention cycles. Hemoglobin was measured at the beginning and at the end of the study. The results showed that the bleeding duration and severity diminished in both groups. No significant difference was observed between two groups in severity of bleeding after intervention (Cohen's d = .24), but duration of bleeding in mefenamic acid group was reduced significantly in comparison with plantain group (Cohen's d = .57). Although mean hemoglobin alterations in mefenamic acid group had a significant difference before and after the intervention, there was no significant difference between the two groups in mean hemoglobin alterations postintervention. Plantain syrup could be suggested as a complementary treatment for HMB, but further studies are required.     

TCR signal strength defines distinct mechanisms of T cell dysfunction and cancer evasion

T cell receptor (TCR) signal strength is a key determinant of T cell responses. We developed a cancer mouse model in which tumor-specific CD8 T cells (TST cells) encounter tumor antigens with varying TCR signal strength. High-signal-strength interactions caused TST cells to up-regulate inhibitory receptors (IRs), lose effector function, and establish a dysfunction-associated molecular program. TST cells undergoing low-signal-strength interactions also up-regulated IRs, including PD1, but retained a cell-intrinsic functional state. Surprisingly, neither high- nor low-signal-strength interactions led to tumor control in vivo, revealing two distinct mechanisms by which PD1^hi TST cells permit tumor escape; high signal strength drives dysfunction, while low signal strength results in functional inertness, where the signal strength is too low to mediate effective cancer cell killing by functional TST cells. CRISPR-Cas9–mediated fine-tuning of signal strength to an intermediate range improved anti-tumor activity in vivo. Our study defines the role of TCR signal strength in TST cell function, with important implications for T cell–based cancer immunotherapies.     

Exploring brain connectivity changes in major depressive disorder using functional‐structural data fusion: A CAN‐BIND‐1 study

There is a growing interest in examining the wealth of data generated by fusing functional and structural imaging information sources. These approaches may have clinical utility in identifying disruptions in the brain networks that underlie major depressive disorder (MDD). We combined an existing software toolbox with a mathematically dense statistical method to produce a novel processing pipeline for the fast and easy implementation of data fusion analysis (FATCAT‐awFC). The novel FATCAT‐awFC pipeline was then utilized to identify connectivity (conventional functional, conventional structural and anatomically weighted functional connectivy) changes in MDD patients compared to healthy comparison participants (HC). Data were acquired from the Canadian Biomarker Integration Network for Depression (CAN‐BIND‐1) study. Large‐scale resting‐state networks were assessed. We found statistically significant anatomically‐weighted functional connectivity (awFC) group differences in the default mode network and the ventral attention network, with a modest effect size (d < 0.4). Functional and structural connectivity seemed to overlap in significance between one region‐pair within the default mode network. By combining structural and functional data, awFC served to heighten or reduce the magnitude of connectivity differences in various regions distinguishing MDD from HC. This method can help us more fully understand the interconnected nature of structural and functional connectivity as it relates to depression.