Sodium fluorescein and 5-aminolevulinic acid fluorescence- guided biopsy in brain lesions: a systematic review and meta-analysis.

PURPOSE: Stereotactic brain biopsies are highly efficient for diagnosing intracerebral pathologies, particularly when surgical resection is infeasible. Fluorescence-based agents such as 5-aminolevulinic acid (5-ALA) and fluorescein sodium (NaFl) can enhance diagnostic accuracy and safety, improving the visualization of lesional tissues. This meta-analysis aimed to evaluate their effect on diagnostic yield and complication rates of brain biopsies. METHODS: This study adhered to Cochrane and PRISMA guidelines. We assessed studies for diagnostic yield and complication rates. Data was analyzed using a random-effects model in RStudio. Diagnostic accuracy measures such as sensitivity and predictive values were calculated based on fluorescence visibility in biopsy samples. RESULTS: Thirty-two non-randomized studies were included, comprising 947 patients, with a mean age ranging from 37 to 77 years, and a mean sample number ranging from 1 to 15 specimens. Diagnostic yields were high: 93% for NaFl and 96% for 5-ALA. Major complications occurred in 3% of procedures with both agents, while minor complications were reported in 7% and 5% with NaFl and 5-ALA respectively. The Negative-predictive-value (NPV) of 5-ALA and NaFl were 8-11% and 60-80% respectively. NaFl demonstrates higher sensitivity and specificity at 84% and 100% compared to 5-ALA's 66%. and 85% respectively. CONCLUSION: 5-ALA and NaFl provide high diagnostic yields with acceptable safety profiles in stereotactic biopsies. NaFl showed higher sensitivity and specificity. NaFl outperforms 5ALA in terms of NPV making it more efficient for small lesions near eloquent regions or major blood vessels. The significance of these findings can be further ascertained through randomized trials.

Large macular hole and autologous retinal transplantation: a systematic review and meta-analysis.

INTRODUCTION: Macular holes are breaks in the retinal tissue at the center of the macula, affecting central vision. The standard treatment involves vitrectomy with membrane peeling and gas tamponade. However, for larger or chronic holes, alternative techniques like autologous retinal graft have emerged. This meta-analysis evaluates the efficacy and safety of retinal transplantation in managing large macular holes. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. The study was prospectively registered in PROSPERO (CRD42024504801). We searched PubMed, Web of Science, Cochrane, and Embase databases for observational studies including individuals with large macular holes with or without retinal detachments and retinal transplantation as the main therapy. We used a random-effects model to compute the mean difference with 95% confidence intervals and performed statistical analysis using R software. RESULTS: We conducted a comprehensive analysis of 19 studies involving 322 patients diagnosed with various types of macular holes (MHs). These included cohorts with refractory MH, high myopia associated with MH, primary MH, and MH with retinal detachment (RD). The findings were promising, revealing an overall closure rate of 94% of cases (95% CI 88-98, I2 = 20%). Moreover, there was a significant improvement in postoperative visual acuity across all subgroups, averaging 0.45 (95% CI 0.33-0.58 ; I2 = 72%; p < 0.01) overall. However, complications occurred with an overall incidence rate of 15% (95% CI 7-25; I2 = 59%). CONCLUSION: ART for large MH shows promising results, including significant improvements in visual acuity and a high rate of MH closure with low complication risks overall and for subgroups.

Baseline and stress-induced changes in plasma bacterial killing ability against gram-negative bacteria are partially mediated by the complement system in Rhinella diptycha toads.

The plasma bacterial killing ability (BKA) is modulated by the stress response in vertebrates, including amphibians. The complement system is an effector mechanism comprised of a set of proteins present in the plasma that once activated can promote bacterial lysis. Herein, we investigated whether changes in plasma BKA as a result of the acute stress response and an immune challenge are mediated by the complement system in Rhinella diptycha toads. Additionally, we investigated whether the observed changes in plasma BKA are associated with changes in plasma corticosterone levels (CORT). We subjected adult male toads to a restraint or an immune challenge (with three concentrations of Aeromonas hydrophila heat inactivated), and then evaluated the plasma BKA against A. hydrophila, in vitro. We determined the complement system activity on plasma BKA, by treating the plasma (baseline, 1 h and 24 h post-restraint, and after the immune challenge) with ethylenediaminetetraacetic acid, heat, or protease. Our results showed increased CORT 1 h and 24 h after restraint and decreased plasma BKA 24 h post-restraint. The inhibitors of the complement system decreased the plasma BKA compared with untreated plasma at all times (baseline, 1 h, and 24 h after restraint), demonstrating that the plasma BKA activity is partially mediated by the complement system. The immune challenge increased CORT, with the highest values being observed in the highest bacterial concentration, compared with control. The plasma BKA was not affected by the immune challenge but was demonstrated to be partially mediated by the complement system. Our results demonstrated that restraint and the immune challenge activated the hypothalamus-pituitary-interrenal axis, by increasing plasma CORT levels in R. diptycha. Also, our results demonstrated the complement system is participative in the plasma BKA for baseline and post-stress situations in these toads.

Corticosterone treatment results in fat deposition and body mass maintenance without effects on feeding behaviour or immunity in female lizards (Tropidurus catalanensis).

Throughout life, animals must maintain homeostasis while coping with challenging events. The period after reproduction can be challenging for oviparous females to maintain homeostasis since they direct most of their energy stores to vitellogenesis, possibly increasing the vulnerability to stressors. Changes in glucocorticoids' (GC) secretion promote various behavioural and physiological adjustments daily and to restore balance after facing stressors. However, when GC are elevated for extended periods, which usually occurs in response to chronic exposure to stressors, they can affect feeding behaviour and suppress the immune function. We aim to elucidate the effects of chronic corticosterone (CORT) exposure on feeding behaviour, body condition and immune function in female lizards, Tropidurus catalanensis, in the post-reproductive period. Thirty animals were divided into three groups: 1. Control (no experimental procedure performed); 2. Empty Implant (animals implanted with empty silastic tube); and 3. CORT Implant (animals implanted with silastic tube filled with CORT, with a chronic continuous release for at least a week). CORT plasma levels feeding behaviour, body condition (body index [BI] and fat index [FI]), leukocyte count, and several immune function variables (bacterial killing ability [BKA], hemagglutination titer, phytohemagglutinin [PHA] immune challenge and leukocyte count) were evaluated. After implantation, CORT treated animals maintained stable body mass through the experiment, while Control and Empty Implant groups displayed weight loss. In the CORT treated animals, there was also a positive relation between BI and FI, and higher FI when compared to groups 1 and 2. No effects of CORT were observed on feeding behaviour nor on the immune function.

Radiosurgical thalamotomy for the management of tremors: a systematic review and meta-analysis.

Medical treatment for tremors may include beta-blockers, primidone, dopaminergic, and anticholinergic drugs but it frequently leads to pharmacoresistance. Therefore, surgical treatment gained relevance as an alternative for those patients.We aim to evaluate radiosurgical thalamotomy as an effective and safe alternative to manage tremors. Pubmed (MEDLINE), Embase, Web of Science, and the Cochrane Library databases were systematically searched for potential articles that evaluated radiosurgical thalamotomy for the management of tremor. Our analysis included 12 studies with 545 patients, 226 of whom were female. Of these, 64.6% of patients were diagnosed with essential tremor (ET), 34.6% with Parkinson's disease (PD), and 0.8% with both ET and PD. The FTM-TRS global score (MD -5.46; 95% CI [-10.44]-[-0.47]; I2 = 52%) and the drawing (MD -1.40; 95% CI [-2.03]-[-0.76]; I2 = 93%), drinking (MD -1.60; 95% CI [-1.82]-[-1.37]; I2 = 40%), and writing (MD -1.51; 95% CI [-1.89]-[-1.13]; I2 = 89%) grades showed significantly lower mean differences, favoring radiosurgical thalamotomy. A pooled proportion of 12% presented with tremor unchanged, while 38% presented with total elimination of tremor. Adverse events included: major paresis, minor paresis, dysarthria, and numbness. Thus, radiosurgical thalamotomy is a safe alternative for tremors resistant to medication, particularly in high-risk patients for RF or DBS procedures. The recommended dose of 130 to 150 Gy is effective and well-tolerated. However, randomized controlled trials (RCTs) are needed to understand the unpredictability of tissue response to radiation.

Dehydration followed by restraint sustains high circulating corticosterone and improves immunity in toads.

Amphibians are suffering population declines due to a variety of factors such as increased ultraviolet radiation, climate change, habitat loss, pathogens, and pollution, or a combination of these. Such changes are associated with a reduction in the availability of water, exposing these animals to a greater risk of desiccation. In this context, understanding how dehydration can modulate the hypothalamic-pituitary-interrenal axis (HPI) and the immune response is an imperative question to predict how stressors can affect amphibian species. We investigated whether dehydration promotes long-lasting effects on toads' ability to respond to a consecutive stressor (restraint) even if the toads are allowed to rehydrate, as well as its effects on the immune function. We also tested the hypothesis that the toads showing more severe dehydration would exhibit lower responsiveness to restraint challenge, even if the animals were allowed to rehydrate. Individuals of R. ornata were dehydrated mildly and severely. Thereafter, they were submitted to a restraint stress challenge for 1 and 24 h. Our results show that dehydration increased hematocrit and CORT in R. ornata toads. The restraint induced an acute stress response in fully hydrated toads (increased CORT and neutrophil: lymphocyte ratio). Otherwise, restraint in moistened cloth bags allowed full rehydration in previously dehydrated toads and did not induce an additional increase in CORT, but those toads sustained elevated CORT up to 24 h of restraint. Also, these animals showed increased neutrophil: lymphocyte ratio and the phagocytic activity of blood cells, even when they rehydrated during restraint. These results point to a continuous activation of the HPA during dehydration and subsequent restraint, even when they recovered from the dehydration state. Also, acute stressors seem to promote immune cell redistribution and augmentation of immune cellular function in R. ornata toads.

Efficacy and safety of adenosine, rapid ventricular pacing and hypothermia in cerebral aneurysms clipping: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Cerebral aneurysms in complex anatomical locations and intraoperative rupture can be challenging. Many methods to reduce blood flow can facilitate its exclusion from the circulation. This study evaluated the safety and efficacy of using adenosine, rapid ventricular pacing, and hypothermia in cerebral aneurysm clipping. METHODS: Databases (PubMed, Embase, and Web of Science) were systematically searched for studies documenting the use of adenosine, rapid ventricular pacing, and hypothermia in cerebral aneurysm clipping and were included in this single-arm meta-analysis. The primary outcome was 30-day mortality. Secondary outcomes included neurological outcomes by mRs and GOS, and cardiac outcomes. We evaluated the risk of bias using ROBIN-I, a tool developed by the Cochrane Collaboration. OpenMetaAnalyst version 2.0 was used for statistical analysis and I2 measured data heterogeneity. Heterogeneity was defined as an I2 > 50%. RESULTS: Our systematic search yielded 10,100 results. After the removal of duplicates and exclusion by title and abstract, 64 studies were considered for full review, of which 29 were included. The overall risk of bias was moderate. The pooled proportions of the adenosine analysis for the different outcomes were: For the primary outcome: 11,9%; for perioperative arrhythmia: 0,19%; for postoperative arrhythmia: 0,56%; for myocardial infarction incidence: 0,01%; for follow-up good recovery (mRs 0-2): 88%; and for neurological deficit:14.1%. In the rapid ventricular pacing analysis, incidences were as follows: peri operative arrhythmia: 0,64%; postoperative arrhythmia: 0,3%; myocardial infarction: 0%. In the hypothermia analysis, the pooled proportion of 30-day mortality was 11,6%. The incidence of post-op neurological deficits was 35,4% and good recovery under neurological analysis by GOS was present in 69.2%. CONCLUSION: The use of the three methods is safe and the related complications were very low. Further studies are necessary, especially with comparative analysis, for extended knowledge.

Baseline and stress-induced steroid plasma levels and immune function vary annually and are associated with vocal activity in male toads (Rhinella icterica).

Theoretical models predict that elevated androgen and glucocorticoid levels in males during the reproductive season promote immunosuppression. However, some studies report decreased stress response during this season. This study investigated annual variation in plasma corticosterone and testosterone levels, plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR) in free-living male toads (Rhinella icterica). Toads were sampled in the field (baseline) and 1 h-post restraint over five months, and we considered the occurrence of vocal activity. Baseline corticosterone, testosterone, and BKA showed higher values during the reproductive period, specifically in calling male toads. The NLR was similar throughout the year, but higher values were observed in calling toads. Moreover, baseline NLR and BKA were positively correlated with both testosterone and corticosterone, suggesting higher steroid levels during reproduction are associated with enhanced cellular and humoral immunity. Despite fluctuation of baseline values, post-restraint corticosterone levels remained uniform over the year, indicating that toads reached similar maximum values throughout the year. Testosterone levels decreased following restraint before one specific reproductive period but increased in response to restraint during and after this period. Meanwhile, BKA decreased due to restraint only after the reproductive period, indicating immune protection and resilience to immunosuppression by stressors associated with steroid hormones during reproduction. Our results show that baseline and stress-induced hormonal and immune regulation varies throughout the year and are associated with vocal activity in R. icterica males, indicating a possible compromise between steroids and immune function in anuran males.

Immune-pineal-ocular axis in amphibians: unveiling a novel connection?

Melatonin is a hormone known as an endogenous temporal marker signaling the dark phase of the day. Although the eyes seem to be the main site of melatonin production in amphibians, little information is available about the natural variation in the ocular melatonin levels and its modulation following immune stimulation. We investigated the daily variation of plasma and ocular melatonin levels in bullfrogs (Lithobates catesbeianus) and their modulation following an immune stimulation with lipopolysaccharide (LPS) in yellow cururu toads (Rhinella icterica). For the daily variation, bullfrogs were bled and then euthanized for eye collection every 3h over 24h to determine plasma and ocular melatonin levels. We found a positive correlation between ocular and plasma melatonin levels, with maximum values at night (22h) for both plasma and the eyes. For immune stimulation, yellow cururu toads received an intraperitoneal injection of LPS or saline solution during the day (10h) or at night (22h). Two hours after injection, toads were bled and euthanized for eye collection to obtain plasma and ocular melatonin levels. In addition, the liver and bone marrow were collected to investigate local melatonin modulation. Our results demonstrate that retina light-controlled rhythmic melatonin production is suppressed while liver and bone marrow melatonin levels increase during the inflammatory assemblage in anurans. Interestingly, the LPS injection decreased only ocular melatonin levels, reinforcing the central role of the eyes (i.e., retina) as an essential organ of melatonin production, and a similar role to the pineal gland during the inflammatory response in amphibians. Together, these results point to a possible immune-pineal-ocular axis in amphibians, yet to be fully described in this group.

Is time really brain in stroke therapy?: A meta-analysis of mechanical thrombectomy up to 155 h post ictus.

BACKGROUND AND OBJECTIVES: Mechanical thrombectomy (MT) has been established as the gold standard of treatment for patients with Acute Ischemic Stroke (AIS) who present up to 6 h after the onset of the stroke. Recently, the DEFUSE-3 and DAWN trials established the safety of starting the MT procedure up to 16 and 24 h after the patient was last seen well, respectively. The purpose of this study is to assess the safety and functional effects of thrombectomy in individuals with AIS detected at a late stage (> 24 h). MATERIALS AND METHODS: PubMed, Web of Science, Embase, and Cochrane databases were thoroughly searched for research on MT in patients in the extremely late time window after AIS. The primary outcomes were symptomatic cerebral hemorrhage, 90-day mortality, Thrombolysis in Cerebral Infarction (TICI) 2b-3, and Modified Rankin Scale (mRS) 0-2. RESULTS: Our study included fifteen studies involving a total of 1,221 patients who presented with AIS and an extended time window. The primary outcome of interest was the favorable functional outcome, mRS 0-2 at 90 days. The pooled proportion for this outcome was 45% (95% confidence interval 34-58%). Other outcomes included the TICI 2b or 3 (successful recanalization), which was reported in 12 studies and had a 79% incidence in the study population (95% CI 68-87%). Complications included: symptomatic intracranial hemorrhage (sICH), which revealed an incidence of 7% in the study population (95% CI 5-10%); and 90-day mortality, which reported a 27% incidence (95% CI 24-31%). In addition, we conducted a comparative analysis between endovascular treatment and standard medical therapy. CONCLUSION: Our meta-analysis provides evidence that supports the need of further randomized and prospective clinical trials to better assess the effectiveness and safety of MT in these patients.

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Immune and endocrine alterations at the early stage of inflammatory assemblage in toads after stimulation with heat-killed bacteria (Aeromonas hydrophila).

The red-leg syndrome in amphibians is a condition commonly associated with the bacteria Aeromonas hydrophila and has led to population declines. However, there is little information concerning the inflammatory assemblage in infected anurans. We evaluated immune and endocrine alterations induced by stimulation with heat-killed A. hydrophila injected in Rhinella diptycha toads. Control animals were not manipulated, while the others were separated into groups that received intraperitoneal injection of 300 µl of saline or heat-killed bacteria: groups A1 (3 × 107 cells), A2 (3 × 108 cells), and A3 (3 × 109 cells). Animals were bled and euthanized six hours post-injection. We evaluated neutrophil: lymphocyte ratio (NLR), plasma bacterial killing ability (BKA), testosterone (T), melatonin (MEL), and corticosterone (CORT) plasma levels. Heat-killed A. hydrophila increased CORT and NLR, and decreased MEL, especially at higher concentrations. There was no effect of treatment on T and BKA. We then selected the saline and A3 groups to conduct mRNA expression of several genes including glucocorticoid receptor (GR), toll-like receptor-4 (TLR-4), interferon-γ (IFN-γ), interleukin (IL)-1ß, IL-6, and IL-10. We found higher expression of IL-6, IL-1ß, IL-10, and IFN-γ in group A3 compared to the saline group. These results indicate the beginning of an inflammatory assemblage, notably at the two highest concentrations of bacteria, and give a better understanding of how anurans respond to an infection within an integrated perspective, evaluating different physiological aspects. Future studies should investigate later phases of the immune response to elucidate more about the inflammation in amphibians challenged with A. hydrophila.

7-Dehydrocholesterol is an endogenous suppressor of ferroptosis.

Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2. Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation3, we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.

Intrauterine Correction of Fetal Myelomeningocele Through Minihysterotomy.

Spina bifida is the most common congenital central nervous system anomaly, resulting in lifelong neurologic, urinary, motor, and bowel disability.1 Its most frequent form is myelomeningocele, characterized by spinal cord extrusion into a sac filled with cerebrospinal fluid.1 We report the case of a 28-year-old pregnant female with no comorbidities. At 16 weeks of pregnancy, fetal ultrasound presented ventriculomegaly, cerebellar herniation, and lumbar myelomeningocele. At 22 weeks, intrauterine surgical correction was performed (Video 1). A minihysterotomy spanning approximately 3 cm was performed. The defect was opened, and the neural placode was dissected and released. This was followed by the isolation of the peripheric dura, which was molded into a tube and closed with watertight suture. Finally, the minihysterotomy was sutured and the skin was closed. The pregnancy followed its course with no complications, and the child was born at term with the lesion closed and no necessity of intensive care. Recent studies have demonstrated that infants who undergo open in utero myelomeningocele repair have better neurologic outcomes than those who are treated after birth.1,2 However, maternal morbidity is nonnegligible with the classical open surgery.2 Peralta et al2 propose a modification of the classic 6.0- to 8.0-cm hysterotomy in which the same multilayer correction of the spinal defect is performed through a 2.5- to 3.5-cm hysterotomy. This modification, called minihysterotomy, has been successfully performed outside of its creation center and was associated with reduced risks of preterm delivery and maternal, fetal, and neonatal complications.2,3.

Early ambulation versus prolonged bed rest for incidental durotomies in spine procedures: a systematic review and meta-analysis.

Incidental durotomies are frequent complications of spine surgery associated with cerebrospinal fluid (CSF) leak-related symptoms. Management typically involves prolonged bed rest to reduce CSF pressure at the durotomy site. However, early ambulation may be a safer, effective alternative. PubMed, Web of Science, Embase, Cochrane, and Scopus were systematically searched for studies comparing early ambulation (bed rest ≤ 24 h) with prolonged bed rest (> 24 h) for patients with incidental durotomies in spine surgeries. The outcomes of interest were CSF leak, hypotensive headache, additional surgical repair, pseudomeningocele, and pulmonary complications. Systematic reviews and meta-analysis were performed following the Cochrane Handbook for Systematic Reviews of Interventions. We included a total of 704 patients from 6 studies. There was a significant reduction in the incidence of pulmonary complications (RR 0.23; 95% CI 0.08-0.67; p = 0.007) in the early mobilization group. The incidence of CSF leak (RR 1.34; 95% CI 0.83-2.14; p = 0.23), hypotensive headache (RR 0.72; 95% CI 0.27-1.90; p = 0.50), additional repair surgery (RR 1.29; 95% CI 0.76-2.2; p = 0.35), and pseudomeningocele (RR 1.29; 95% CI 0.20-8.48; p = 0.79) did not differ significantly. In patients with incidental durotomy following spinal surgery, early mobilization was associated with a lower incidence of pulmonary complications as compared with prolonged bed rest. There was no significant difference between groups in terms of CSF leak, need for additional repair, pseudomeningocele, and hypotensive headache.

The effect of increased positive end expiratory pressure on brain tissue oxygenation and intracranial pressure in acute brain injury patients.

Cerebral hypoxia is an important cause of secondary brain injury. Improving systemic oxygenation may increase brain tissue oxygenation (PbtO2). The effects of increased positive end-expiratory pressure (PEEP) on PbtO2 and intracranial pressure (ICP) needs to be further elucidated. This is a single center retrospective cohort study (2016-2021) conducted in a 34-bed Department of Intensive Care unit. All patients with acute brain injury under mechanical ventilation who were monitored with intracranial pressure and brain tissue oxygenation (PbtO2) catheters and underwent at least one PEEP increment were included in the study. Primary outcome was the rate of PbtO2 responders (increase in PbtO2 > 20% of baseline) after PEEP increase. ΔPEEP was defined as the difference between PEEP at 1 h and PEEP at baseline; similarly ΔPbtO2 was defined as the difference between PbtO2 at 1 h after PEEP incrementation and PbtO2 at baseline. We included 112 patients who underwent 295 episodes of PEEP increase. Overall, the median PEEP increased form 6 (IQR 5-8) to 10 (IQR 8-12) cmH2O (p = 0.001), the median PbtO2 increased from 21 (IQR 16-29) mmHg to 23 (IQR 18-30) mmHg (p = 0.001), while ICP remained unchanged [from 12 (7-18) mmHg to 12 (7-17) mmHg; p = 0.42]. Of 163 episode of PEEP increments with concomitant PbtO2 monitoring, 34 (21%) were PbtO2 responders. A lower baseline PbtO2 (OR 0.83 [0.73-0.96)]) was associated with the probability of being responder. ICP increased in 142/295 episodes of PEEP increments (58%); no baseline variable was able to identify this response. In PbtO2 responders there was a moderate positive correlation between ΔPbtO2 and ΔPEEP (r = 0.459 [95% CI 0.133-0.696]. The response in PbtO2 and ICP to PEEP elevations in brain injury patients is highly variable. Lower PbtO2 values at baseline could predict a significant increase in brain oxygenation after PEEP increase.

Testosterone immunomodulation in free-living and captive Rhinella icterica male toads.

Testosterone (T) regulates immune function, with both immunostimulatory and immunosuppressive effects on several vertebrates. We investigated the covariation between plasma T and corticosterone (CORT) levels and immunity (plasma bacterial killing ability (BKA), and neutrophil to lymphocyte ratio (NLR)) in free-living Rhinella icterica male toads inside and outside the reproductive season. We found an overall positive correlation between steroids and immune traits, with toads during the reproductive season displaying increased T, CORT and BKA. We also investigated the T transdermal application effects on T, CORT, phagocytosis of blood cells, BKA and NLR in captive toads. Toads were treated with T (1, 10 or 100 µg) or vehicle (sesame oil) for eight consecutive days. Animals were bled on the first and eighth days of treatment. Increased plasma T was observed on the first and last day of T-treatment, while increased BKA was observed following all T doses on the last day, with a positive correlation between T and BKA. Plasma CORT, NLR and phagocytosis increased on the last day for all T-treated and vehicle groups. Overall, we demonstrated a positive covariation between T and immune traits in the field and T-induced augmented BKA in captive toads, indicating a T immunoenhancing effect in R. icterica males. This article is part of the theme issue 'Amphibian immunity: stress, disease and ecoimmunology'.