The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review.

OBJECTIVES: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. METHODS: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. RESULTS: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). CONCLUSION: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.

TikTok Promotes Diet Culture and Negative Body Image Rhetoric: A Content Analysis.

OBJECTIVE: This study aimed to explore the presence of body image and diet culture rhetoric in videos under the hashtag #HealthyLifestyle on TikTok. METHODS: The top 250 videos under #HealthyLifestyle were categorized using a codebook of wellness topics. We conducted descriptive statistics and interrater reliability analysis. RESULTS: #HealthyLifestyle videos had high rates of all coded categories, including negative and positive messages about body image and diet culture. Nearly all content with positive connotations was counteracted by coexisting negative messaging. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that content under #HealthyLifestyle contains messaging conflicting with the definition of a healthy lifestyle. Considering the young audience consuming this content, improved nutrition education and health literacy in schools is essential.

Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis.

BACKGROUND: There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8-93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9 m, 95% CI 25.9-73.8 m) and riociguat (49.5 m, 95% CI 17.3-81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty). CONCLUSION: Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.

Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis and there are few evidence-based drug therapies that reduce mortality. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to assess whether sildenafil reduces mortality, disease progression and adverse side effects. METHODS: We reviewed randomized controlled studies (RCTs) from MEDLINE, Cochrane registry of clinical trials, and EMBASE. Our outcomes of interest included mortality, change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance fixed effects meta-analysis method to calculate pooled relative risk (RR) and mean difference (MD). RESULTS: A total of 4 studies were included in the systematic review. Sildenafil probably reduces mortality when compared to placebo or to standard care, [RR 0.73 (95% CI 0.51 to 1.04); moderate certainty]. Pooled estimates showed sildenafil may not alter the rate of change of FVC [MD 0.61% (95% CI -0.29 to 1.52)], or DLCO [MD 0.97% (95% CI 0.04 to 1.90)] (both low certainty). Pooled estimated showed sildenafil may not reduce the number of hospitalizations or acute exacerbations, [RR 1.10 (95% CI 0.61 to 1.98); low certainty]. There is probably no difference in drug discontinuation due to adverse effects when comparing sildenafil to the control group, [RR 0.79 (95% CI 0.56, 1.10); moderate certainty]. CONCLUSION: Sildenafil probably reduces all-cause mortality in IPF patients. More studies need to be done to confirm the magnitude and reliability of the point estimate.

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework. RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty). CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

Evolution and developmental plasticity of lung structure in high-altitude deer mice.

Hypoxia at high altitudes can constrain the ability of endotherms to maintain sufficient rates of pulmonary O2 transport to support exercise and thermogenesis. Hypoxia can also impede lung development during early post-natal life in some mammals, and could thus accentuate constraints on O2 transport at high altitude. We examined how these challenges are overcome in deer mice (Peromyscus maniculatus) native to high altitude. Lung structure was examined in highland and lowland populations of deer mice and lowland populations of white-footed mice (P. leucopus; a congener restricted to low altitude) that were bred in captivity. Among mice that were born and raised to adulthood in normoxia, highland deer mice had higher alveolar surface density and more densely packed alveoli. The increased alveolar surface density in highlanders became fully apparent at juvenile life stages at post-natal day 30 (P30), after the early developmental period of intense alveolus formation before P21. Alveolar surface density was maintained in highlanders that were conceived, born, and raised in hypoxia (~ 12 kPa O2), suggesting that lung development was not impaired by post-natal hypoxia as it is in many other lowland mammals. However, developmental hypoxia increased lung volume and thus augmented total alveolar surface area from P14. Overall, our findings suggest that evolutionary adaptation and developmental plasticity lead to changes in lung morphology that should improve pulmonary O2 uptake in deer mice native to high altitude.

Iatrogenic neurological injury in children with trisomy 21.

PURPOSE: Children with trisomy 21 are at a greater risk for craniocervical junction instability than the general population. These children frequently require administration of anesthesia due to surgical (including otolaryngological) interventions and are at risk for neurological injury. We reviewed the current literature describing iatrogenic neurological injury in children with trisomy 21 undergoing anesthesia in order to facilitate the development of safety recommendations. METHODS: A systematic review of the literature was performed using Medline, Embase, Scopus, and Google Scholar, following the PRISMA statement. All cases of perioperative neurological injury in children with trisomy 21, aged 18 and under were identified. Clinical and radiographic data were extracted for each report. The data were synthesized to develop recommendations regarding perioperative management. RESULTS: Of 348 articles screened, 16 cases of iatrogenic neurological injury (in children ages 0.7-18 years) were identified. Three injuries occurred during otolaryngological surgeries, nine during sedation for intubation for non-otolaryngological surgery, one during sedation for neuroimaging, one while restraining a child, and two were due to intraoperative head and neck positioning while anesthetized. Preoperative screening was reported in four cases. A diagnosis of atlantoaxial instability (AAI) or atlantooccipital instability (AOI) was made immediately following symptom presentation in three cases but was often delayed by a median (IQR) of 30(11.5-912.5) days. No cases resolved spontaneously, with 2 patients progressing to brain death and 12 requiring surgical stabilization. Of the latter, seven showed improvement, whereas one died 5 months later. No intraoperative precautions during the index procedure were reported in any of the 16 cases. CONCLUSION: Iatrogenic neurological injury in children with trisomy 21 are rare but severe and likely under reported. Although the role of preoperative screening remains controversial, all children with trisomy 21 undergoing surgery should be considered at risk for neurological injury due to confirmed or undiagnosed AAI or AOI and should be transferred and positioned with appropriate caution. Children with instability should be referred for neurosurgical attention for preoperative stabilization to mitigate perioperative risk. It is imperative to consider the possibility of neurological injury secondary to medical procedures, as it is clear that neck manipulation of any sort places these children at risk.