Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

TCD assessment in fulminant hepatic failure: Improvements in cerebral autoregulation after liver transplantation.

INTRODUCTION AND OBJECTIVES: Acute liver failure, also known as fulminant hepatic failure (FHF), includes a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction and hepatic encephalopathy. The objective of this study was to assess cerebral autoregulation (CA) in 25 patients (19 female) with FHF and to follow up with seventeen of these patients before and after liver transplantation. PATIENTS AND METHODS: The mean age was 33.8 years (range 14-56, SD 13.1 years). Cerebral hemodynamics was assessed by transcranial Doppler (TCD) bilateral recordings of cerebral blood velocity (CBv) in the middle cerebral arteries (MCA). RESULTS: CA was assessed based on the static CA index (SCAI), reflecting the effects of a 20-30 mmHg increase in mean arterial blood pressure on CBv induced with norepinephrine infusion. SCAI was estimated at four time points: pretransplant and on the 1st, 2nd and 3rd posttransplant days, showing a significant difference between pre- and posttransplant SCAI (p = 0.005). SCAI peaked on the third posttransplant day (p = 0.006). Categorical analysis of SCAI showed that for most patients, CA was reestablished on the second day posttransplant (SCAI > 0.6). CONCLUSIONS: These results suggest that CA impairment pretransplant and on the 1st day posttransplant was re-established at 48-72 h after transplantation. These findings can help to improve the management of this patient group during these specific phases, thereby avoiding neurological complications, such as brain swelling and intracranial hypertension.

Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Critical Closing Pressure and Cerebrovascular Resistance Responses to Intracranial Pressure Variations in Neurocritical Patients.

BACKGROUND: Critical closing pressure (CrCP) and resistance-area product (RAP) have been conceived as compasses to optimize cerebral perfusion pressure (CPP) and monitor cerebrovascular resistance, respectively. However, for patients with acute brain injury (ABI), the impact of intracranial pressure (ICP) variability on these variables is poorly understood. The present study evaluates the effects of a controlled ICP variation on CrCP and RAP among patients with ABI. METHODS: Consecutive neurocritical patients with ICP monitoring were included along with transcranial Doppler and invasive arterial blood pressure monitoring. Internal jugular veins compression was performed for 60 s for the elevation of intracranial blood volume and ICP. Patients were separated in groups according to previous intracranial hypertension severity, with either no skull opening (Sk1), neurosurgical mass lesions evacuation, or decompressive craniectomy (DC) (patients with DC [Sk3]). RESULTS: Among 98 included patients, the correlation between change (Δ) in ICP and the corresponding ΔCrCP was strong (group Sk1 r = 0.643 [p = 0.0007], group with neurosurgical mass lesions evacuation r = 0.732 [p < 0.0001], and group Sk3 r = 0.580 [p = 0.003], respectively). Patients from group Sk3 presented a significantly higher ΔRAP (p = 0.005); however, for this group, a higher response in mean arterial pressure (change in mean arterial pressure p = 0.034) was observed. Exclusively, group Sk1 disclosed reduction in ICP before internal jugular veins compression withholding. CONCLUSIONS: This study elucidates that CrCP reliably changes in accordance with ICP, being useful to indicate ideal CPP in neurocritical settings. In the early days after DC, cerebrovascular resistance seems to remain elevated, despite exacerbated arterial blood pressure responses in efforts to maintain CPP stable. Patients with ABI with no need of surgical procedures appear to remain with more effective ICP compensatory mechanisms when compared with those who underwent neurosurgical interventions.

Noninvasive intracranial pressure waveforms for estimation of intracranial hypertension and outcome prediction in acute brain-injured patients.

Analysis of intracranial pressure waveforms (ICPW) provides information on intracranial compliance. We aimed to assess the correlation between noninvasive ICPW (NICPW) and invasively measured intracranial pressure (ICP) and to assess the NICPW prognostic value in this population. In this cohort, acute brain-injured (ABI) patients were included within 5 days from admission in six Intensive Care Units. Mean ICP (mICP) values and the P2/P1 ratio derived from NICPW were analyzed and correlated with outcome, which was defined as: (a) early death (ED); survivors on spontaneous breathing (SB) or survivors on mechanical ventilation (MV) at 7 days from inclusion. Intracranial hypertension (IHT) was defined by ICP > 20 mmHg. A total of 72 patients were included (mean age 39, 68% TBI). mICP and P2/P1 values were significantly correlated (r = 0.49, p < 0.001). P2/P1 ratio was significantly higher in patients with IHT and had an area under the receiving operator curve (AUROC) to predict IHT of 0.88 (95% CI 0.78-0.98). mICP and P2/P1 ratio was also significantly higher for ED group (n = 10) than the other groups. The AUROC of P2/P1 to predict ED was 0.71 [95% CI 0.53-0.87], and the threshold P2/P1 > 1.2 showed a sensitivity of 60% [95% CI 31-83%] and a specificity of 69% [95% CI 57-79%]. Similar results were observed when decompressive craniectomy patients were excluded. In this study, P2/P1 derived from noninvasive ICPW assessment was well correlated with IHT. This information seems to be as associated with ABI patients outcomes as ICP.Trial registration: NCT03144219, Registered 01 May 2017 Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT03144219 .

Use of tannin extract as a strategy to reduce methane in Nellore and Holstein cattle and its effect on intake, digestibility, microbial efficiency and ruminal fermentation.

This study was carried out to evaluate the use of tannin extract from Acacia mearnsii as a strategy to reduce methane (CH4 ) in two distinct cattle genotypes and its effect on intake, digestibility, microbial efficiency and ruminal fermentation. Four Nellore (Bos indicus) and four Holstein (Bos taurus) dry cows fitted with rumen cannula were assigned to two 4 × 4 Latin square design, in a 2 × 4 factorial arrangement, where each genotype represented a square receiving four tannin levels (commercial extract of A. mearnsii) in the diet (0%, 0.5%, 1.0% and 1.5% of dry matter). Tannin levels used did not cause a reduction in feed intake or rumen passage rate for both genotypes (p > 0.05), although there was a linear reduction in the degradation rate and ruminal disappearance of diet (p < 0.05). The increase in tannin levels reduced the amount of entodiniomorph protozoa in the Nellore cattle (p < 0.05). There was no change in N retention or microbial efficiency (p > 0.05), despite the linear reduction of nutrient digestibility and the synthesis of microbial nitrogen (p < 0.05). The ruminal CH4 production was reduced (p < 0.05) without reducing the short-chain fatty acid production. The threshold of 0.72% of tannin in the diet was estimated as the starting point for the reduction of ruminal CH4 production with long-term efficacy. Therefore, the use of low levels of tannin extract from A. mearnsii is a potential option to manipulate rumen fermentation in Nellore and Holstein cattle and needs to be further investigated.

The influence of intracranial hypertension on static cerebral autoregulation.

OBJECTIVES: To analyze the influences of mild and severe intracranial hypertension on cerebral autoregulation (CA). PATIENTS AND METHODS: Duroc piglets were monitored with an intracranial pressure (ICP) catheter. Intracranial hypertension was induced via infusion of 4 or 7 ml of saline solution by a bladder catheter that was inserted into the parietal lobe. The static cerebral autoregulation (sCA) index was evaluated via cerebral blood flow velocities (CBFv). Piglets with ICPs ≤ 25 and > 25 mmHg were considered as group 1 and 2, respectively. Continuous variables were evaluated using the Kolmogorov-Smirnov goodness-of-fit test. The main parameters were collected before and after ICH induction and compared using two-factor mixed-design ANOVAs with the factor of experimental group (mild and severe ICH). RESULTS: In group 1 (ICP ≤ 25 mmHg), there were significant differences in sCA (p = .01) and ICP (p = .0002) between the basal and balloon inflation conditions. In group 2 (ICP > 25 mmHg), there were significant differences in CBFv (p = .0072), the sCA index (p = .0001) and ICP (p = .00001) between the basal and balloon inflation conditions. CONCLUSION: We conclude that intracranial hypertension may have a direct effect on sCA.

Pooling data from different populations: should there be regional differences in cerebral haemodynamics?

BACKGROUND: Though genetic and environmental determinants of systemic haemodynamic have been reported, surprisingly little is known about their influences on cerebral haemodynamics. We assessed the potential geographical effect on cerebral haemodynamics by comparing the individual differences in cerebral blood flow velocity (CBFv), vasomotor tone (critical closing pressure- CrCP), vascular bed resistance (resistance-area product- RAP) and cerebral autoregulation (CA) mechanism on healthy subjects and acute ischaemic stroke (AIS) patients from two countries. METHODS: Participants were pooled from databases in Leicester, United Kingdom (LEI) and São Paulo, Brazil (SP) research centres. Stroke patients admitted within 48 h of ischaemic stroke onset, as well as age- and sex-matched controls were enrolled. Beat-to-beat blood pressure (BP) and bilateral mean CBFv were recorded during 5 min baseline. CrCP and RAP were calculated. CA was quantified using transfer function analysis (TFA) of spontaneous oscillations in arterial BP and mean CBFv, and the derived autoregulatory index (ARI). RESULTS: A total of 100 participants (50 LEI and 50 SP) were recruited. No geographical differences were found. Both LEI and SP AIS participants showed lower values of CA compared to controls. Moreover, the affected hemisphere presented lower resting CBFv and higher RAP compared to the unaffected hemisphere in both populations. CONCLUSIONS: Impairments of cerebral haemodynamics, demonstrated by several key parameters, was observed following AIS compared to controls irrespective of geographical region. These initial results should encourage further research on cerebral haemodynamic research with larger cohorts combining different populations.

Cerebral hemodynamics in sepsis assessed by transcranial Doppler: a systematic review and meta-analysis.

Cerebral microcirculation is gradually compromised during sepsis, with significant reductions in the function of capillaries and blood perfusion in small vessels. Transcranial Doppler ultrasound (TCD) has been used to assess cerebral circulation in a typical clinical setting. This study was to systematically review TCD studies, assess their methodological quality, and identify trends that can be associated with the temporal evolution of sepsis and its clinical outcome. A meta-analysis of systematic reviews was conducted according to the PRISMA statement. Articles were searched from 1982 until the conclusion of this review in December 2015. Twelve prospective and observational studies were selected. Evaluations of cerebral blood flow, cerebral autoregulation, and carbon dioxide (CO2) vasoreactivity were summarized. A temporal pattern of the evolution of the illness was found. In early sepsis, the median blood flow velocity (Vm) and pulsatility index (PI) increased, and the cerebral autoregulation (CA) remained unchanged. In contrast, Vm normalization, PI reduction and CA impairment were found in later sepsis (patients with severe sepsis or septic shock). Cerebral haemodynamic is impaired in sepsis. Modifications in cerebral blood flow may be consequence to the endothelial dysfunction of the microvasculature induced by the release of inflammatory mediators. A better understanding of cerebral hemodynamics may improve the clinical management of patients with sepsis and, consequently, improve clinical outcomes.

Analysis of Dental Enamel Surface Submitted to Fruit Juice Plus Soymilk by Micro X-Ray Fluorescence: In Vitro Study.

OBJECTIVE: This paper aimed to analyze the in vitro industrialized fruit juices effect plus soy to establish the erosive potential of these solutions. MATERIALS AND METHODS: Seventy bovine incisors were selected after being evaluated under stereomicroscope. Their crowns were prepared and randomly divided into 7 groups, using microhardness with allocation criteria. The crowns were submitted to the fruit juice plus soy during 15 days, twice a day. The pH values, acid titration, and Knoop microhardness were recorded and the specimens were evaluated using X-ray microfluorescence (µXRF). RESULTS: The pH average for all juices and after 3 days was significantly below the critical value for dental erosion. In average, the pH value decreases 14% comparing initial time and pH after 3 days. Comparing before and after, there was a 49% microhardness decrease measured in groups (p < 0.05). Groups G1, G2, G5, and G6 are above this average. The analysis by µXRF showed a decrease of approximately 7% Ca and 4% P on bovine crowns surface. Florida (FL) statistical analysis showed a statistically significant 1 difference between groups. Thus, a tooth chance to suffer demineralization due to industrialized fruit juices plus soy is real.

Puerperal Extracranial Vertebral Artery Dissection and Nonaneurysmal Subarachnoid Hemorrhage.

Previously reported only a few times before, we present a case of extracranial vertebral dissection and spontaneous frontoparietal subarachnoid hemorrhage (SAH) in the puerperium, discussing possible mechanisms and difficulties in management. A 35-year-old woman presented 10 days postcaesarean section with neck pain and vertigo with normal initial investigations. Following recurrent vertigo, headache, and ataxia, imaging revealed a frontoparietal SAH and vertebral artery dissection. The patient was consequently treated with aspirin, and then following a return of symptoms 3 weeks later, warfarin therapy was continued for 6 months. The possible underlying mechanisms for this case are discussed, including reversible cervical vasoconstriction syndrome and posterior reversible encephalopathy syndrome, although neither was identified. The small SAH alongside recurrent posterior circulation symptoms resulted in the initiation of antithrombotic therapy. This report supports studies demonstrating higher incidence of cervicocephalic arterial dissection in the puerperium. Moreover, the heterogeneous presentation and manifestations of such cases require individualized treatment, and warrant studies into underlying mechanisms behind extracranial dissection and nonaneurysmal SAH.

Spindle epithelial tumor with thymus-like element (SETTLE)-Report of a rare thyroid carcinoma.

Spindle epithelial tumor with thymus-like element should be included in the differential diagnosis of thyroid gland cancers, particularly in medullary carcinoma, younger patients and indolent clinical presentation, because it may influence treatment and prognosis.

Electrothermal interfacial evaporation through carbon-nanostructured composite membranes.

High energy demand required in membrane distillation (MD) process to heat feed water and maintain the necessary temperature gradient across the membrane presents a challenge to widespread adoption of MD. In response to this challenge, surface heating membrane distillation (SHMD) has emerged as a promising solution. SHMD can employ solar or electrical energy to directly heat the membrane and feed, eliminating the need for an external heat source to heat feed water. In this study, we explore electrothermally-driven interfacial evaporation using a multi-walled carbon nanotube (MWCNT)-based composite membrane and further envision its utilization for high-efficient SHMD. Upon application of voltage, the resistance of the MWCNT leads to the conversion of electrical energy into heat, which is then uniformly transferred to feeds. The MWCNT-based composite membrane exhibited an evaporative water flux of up to 2.34 kg m-2h-1 with an associated energy efficiency of 61% and demonstrated outstanding localized surface heating performance. The employed membranes exhibited no significant variations in either resistance or surface temperature, regardless of the direction of the applied electric field. Energy parameters from the electrothermal membranes showed quantitative agreement with values reported for various electrothermal MD systems, suggesting the potential of the composite membranes in energy-efficient and cost-effective localized heating MD applications.

The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy.

BACKGROUND: Oxaliplatin, the third-generation platinum compound, has evolved as one of the most important therapeutic agents in colorectal cancer chemotherapy. The main limiting factor in oxaliplatin treatment is painful neuropathy that is difficult to treat. This side effect has been studied for several years, but its full mechanism is still inconclusive, and effective treatment does not exist. Data suggest that oxaliplatin's initial neurotoxic effect is peripheral and oxidative stress-dependent. A spinal target is also suggested in its mechanism of action. The flavonoids rutin and quercetin have been described as cell-protecting agents because of their antioxidant, antinociceptive, and anti-inflammatory actions. We proposed a preventive effect of these agents on oxaliplatin-induced painful peripheral neuropathy based on their antioxidant properties. METHODS: Oxaliplatin (1 mg/kg, i.v.) was injected in male Swiss mice, twice a week (total of nine injections). The development of sensory alterations, such as thermal and mechanical allodynia, was evaluated using the tail immersion test in cold water (10°C) and the von Frey test. Rutin and quercetin (25-100 mg/kg, i.p.) were injected 30 min before each oxaliplatin injection. The animals' spinal cords were removed for histopathological and immunohistochemical evaluation and malondialdehyde assay. RESULTS: Oxaliplatin significantly increased thermal and mechanical nociceptive response, effects prevented by quercetin and rutin at all doses. Fos immunostaining in the dorsal horn of the spinal cord confirmed these results. The oxidative stress assays mainly showed that oxaliplatin induced peroxidation in the spinal cord and that rutin and quercetin decreased this effect. The flavonoids also decreased inducible nitric oxide synthase and nitrotyrosine immunostaining in the dorsal horn of the spinal cord. These results suggest that nitric oxide and peroxynitrite are also involved in the neurotoxic effect of oxaliplatin and that rutin and quercetin can inhibit their effect in the spinal cord. We also observed the preservation of dorsal horn structure using histopathological analyses. CONCLUSIONS: Oxaliplatin induced painful peripheral neuropathy in mice, an effect that was prevented by rutin and quercetin. The mechanism of action of oxaliplatin appears to be, at least, partially oxidative stress-induced damage in dorsal horn neurons, with the involvement of lipid peroxidation and protein nitrosylation.

Evaluation of low-level laser therapy in patients with acute and chronic temporomandibular disorders.

The purpose of this study was to address the following question: among patients with acute or chronic temporomandibular disorders (TMD), does low-level laser therapy (LLLT) reduce pain intensity and improve maximal mouth opening? The sample comprised myogenic TMD patients (according Research Diagnostic Criteria for TMD). Inclusion criteria were: male/female, no age limit, orofacial pain, tender points, limited jaw movements and chewing difficulties. Patients with other TMD subtypes or associated musculoskeletal/rheumatologic disease, missing incisors teeth, LLLT contra-indication, and previous TMD treatment were excluded. According to disease duration, patients were allocated into two groups, acute (<6 months) and chronic TMD (≥ 6 months). For each patient, 12 LLLT sessions were performed (gallium-aluminum-arsenide; λ = 830 nm, P = 40 mW, CW, ED = 8 J/cm(2)). Pain intensity was recorded using a 10-cm visual analog scale and maximal mouth opening using a digital ruler (both recorded before/after LLLT). The investigators were previously calibrated and blinded to the groups (double-blind study) and level of significance was 5% (p < 0.05). Fifty-eight patients met all criteria, 32 (acute TMD), and 26 (chronic TMD). Both groups had a significant pain intensity reduction and maximal mouth opening improvement after LLLT (Wilcoxon test, p < 0.001). Between the groups, acute TMD patient had a more significant pain intensity reduction (Mann-Whitney test, p = 0.002) and a more significant maximal mouth opening improvement (Mann-Whitney test, p = 0.011). Low-level laser therapy can be considered as an alternative physical modality or supplementary approach for management of acute and chronic myogenic temporomandibular disorder; however, patients with acute disease are likely to have a better outcome.

The Role of High-Resolution Ultrasound in the Assessment of Surgical Candidates for Transoral Endoscopic Thyroidectomy Via Vestibular Approach (TOETVA).

The approach of surgical techniques has evolved significantly over the last decade, with natural orifice surgeries replacing traditional open approaches. In 2016, Angkoon Anuwong, in Thailand, demonstrated it was possible to perform thyroidectomies in a series of patients by a transoral endoscopic ap-proach - transoral endoscopy thyroidectomy vestibular approach (TOETVA) - with similar complication rates when compared to conventional surgeries. This transoral surgery has become a safe alternative with better cosmetic results, compared to conventional open-route procedures, like Kocher cervi-cotomy. Indeed, it is an option to surgically treat neoplastic and functional thyroid diseases. The technique is performed through a median incision in the oral vestibule, plus two bilateral incisions, followed by the insertion of three trocars, one centrally for a camera, and two laterally for working instruments. Although revolutionary, TOETVA has its technical limitations. Therefore, it is important to precisely define the preoperative eligibility criteria for this type of surgical approach. High-resolution ultrasound is the first imaging modality for the assessment of thyroid nodules, lymph node metastases and surgical field. The aim of this article is to outline the sonographic technique and the role of high-resolution ultrasound in the presurgical evaluation of TOETVA.

Point-Counterpoint: Cerebral perfusion pressure is a high-risk concept.

Cerebral perfusion pressure (CPP) is calculated as the difference between mean arterial blood pressure and mean intracranial pressure, being commonly applied in neurocritical care. This commentary discusses recent physiological advances in knowledge as well as bedside practice issues that in combination indicate considering CPP under this perspective may lead to inaccurate assumptions and potentially misleading decision making.