Comparison of two pharmacokinetic-pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect.

BACKGROUND: Profound neuromuscular block (NMB) is important in surgeries where complete immobility is considered essential to improve tracheal intubation and surgical conditions. Rocuronium bromide is a commonly used NMB agent. This work describes a noninvasive approach for estimation of post-tetanic count (PTC) based on two pharmacokinetic (PK) models, the Saldien and the De Haes models. The aim was to investigate the rocuronium bromide PK-pharmacodynamic (PD) relationship in estimating the PTC effect during profound NMB. METHODS: In this prospective, non-randomised, observational study, an induction bolus of rocuronium bromide was administered followed by continuous infusion for maintenance of a PTC of 1-2. measured every 3 min. Measurements were analysed as discrete categorical data and by applying the nonlinear mixed-effect modelling approach. Performance of the selected models was evaluated through simulation model-based diagnostics, further assessing the precision of the parameter estimates and the performance of the models at the individual level. RESULTS: Data from 30 adult patients undergoing elective abdominal or neurosurgical procedures were included. Post-tetanic count response profiles during rocuronium bromide infusion were successfully characterised using the population PD analysis. The models showed a good performance for all PTC categories, albeit with a moderate over-prediction of PTC >6. CONCLUSIONS: Our findings indicate that using plasma concentrations of rocuronium bromide estimated with either of the two models, combined with a PD model, provides equal model performance when predicting PTC. These promising results may provide an important advance in guiding rocuronium bromide administration when profound NMB in routine clinical practice is desired.

Enabling Early Obstructive Sleep Apnea Diagnosis With Machine Learning: Systematic Review.

BACKGROUND: American Academy of Sleep Medicine guidelines suggest that clinical prediction algorithms can be used to screen patients with obstructive sleep apnea (OSA) without replacing polysomnography, the gold standard. OBJECTIVE: We aimed to identify, gather, and analyze existing machine learning approaches that are being used for disease screening in adult patients with suspected OSA. METHODS: We searched the MEDLINE, Scopus, and ISI Web of Knowledge databases to evaluate the validity of different machine learning techniques, with polysomnography as the gold standard outcome measure and used the Prediction Model Risk of Bias Assessment Tool (Kleijnen Systematic Reviews Ltd) to assess risk of bias and applicability of each included study. RESULTS: Our search retrieved 5479 articles, of which 63 (1.15%) articles were included. We found 23 studies performing diagnostic model development alone, 26 with added internal validation, and 14 applying the clinical prediction algorithm to an independent sample (although not all reporting the most common discrimination metrics, sensitivity or specificity). Logistic regression was applied in 35 studies, linear regression in 16, support vector machine in 9, neural networks in 8, decision trees in 6, and Bayesian networks in 4. Random forest, discriminant analysis, classification and regression tree, and nomogram were each performed in 2 studies, whereas Pearson correlation, adaptive neuro-fuzzy inference system, artificial immune recognition system, genetic algorithm, supersparse linear integer models, and k-nearest neighbors algorithm were each performed in 1 study. The best area under the receiver operating curve was 0.98 (0.96-0.99) for age, waist circumference, Epworth Somnolence Scale score, and oxygen saturation as predictors in a logistic regression. CONCLUSIONS: Although high values were obtained, they still lacked external validation results in large cohorts and a standard OSA criteria definition. TRIAL REGISTRATION: PROSPERO CRD42021221339; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221339.

Association Among Preoperative Cognitive Performance, Regional Cerebral Oxygen Saturation, and Postoperative Delirium in Older Portuguese Patients.

BACKGROUND: Postoperative delirium is common among older patients and preoperative identification of high-risk patients is widely recommended. The aim of this study was to assess whether preoperative cognitive performance using brief screening tools or regional cerebral oxygen saturation (Scto2) was associated with the development of postoperative delirium in older Portuguese patients undergoing elective surgery. METHODS: Prospective observational cohort study where preoperative cognitive screening tools (Mini-Cog, Mini-Mental State Examination, verbal fluency) and Scto2 (INVOS 5100C; Medtronic, Ireland) were assessed in 238 patients ≥65 years old undergoing elective surgery between July 2017 and May 2019 at a tertiary academic center in Portugal. The primary outcome was postoperative delirium detected by the 3D-Confusion Assessment Method. Data were analyzed by univariate analysis and multivariable logistic regression. RESULTS: Delirium was identified in 53 patients (22%); 162 patients (68%) had completed only 4 years of education. On multivariable analysis, probable cognitive impairment tested by the Mini-Cog (odds ratio [OR] = 1.57; 95% confidence interval [CI], 0.70-3.53; corrected P value >.999), by the Mini-Mental State Examination (OR = 2.75; 95% CI, 1.23-6.13; corrected P value = .052), and by the animal verbal fluency test (OR = 1.24; 95% CI, 0.49-3.16; corrected P value >.999) were not significantly associated with the development of postoperative delirium. In contrast, lower preoperative Scto2 (OR = 1.08; 95% CI, 1.02-1.14; corrected P value = .024 for each point decrease in Scto2) was associated with postoperative delirium. CONCLUSIONS: We did not find enough evidence to suggest that poor preoperative cognitive performance was significantly associated with the development of postoperative delirium in an older Portuguese surgical population with an overall low level of formal education, but rather that preoperative Scto2 may be helpful in identifying patients at risk for delirium.

Effects of varying remifentanil concentrations on Analgesia Nociception Index® under propofol: an observational study.

Analgesia Nociception Index monitor provides a measurement of the nociception and anti-nociception balance based on heart-rate variability. The aim was to assess the ability of Analgesia Nociception Index (ANI) to detect standard noxious stimulation during anesthesia at different opioid concentrations in comparison to hemodynamic and Bispectral Index parameters. Sixteen patients undergoing general anesthesia with propofol and remifentanil. Standardized tetanic electrical stimulation was applied without any other concurrent stimuli, while different effect site concentrations of remifentanil were increased step-by-step (0.5, 1.5, 3.0, 5 and 7 ng/ml). For each tetanic stimulus, values of the different variables 60 s before and 120 s following the stimulus were analyzed. ANI values decreased significantly 120 s after the stimulus when compared to the mean ANI 60 s before the stimulus (P < 0.01). At lower remifentanil concentrations (0.5 ng/ml), all variables except electromyogram from the Bispectral Index significantly changed after the stimulus but in the higher concentrations (5.0 and 7.0 ng/ml) there was not a significant change. The other variables did not change significantly after the noxious stimulation. ANI was the only variable that positively correlated with the different remifentanil concentrations (R = 0.959, P = 0.01). Our study showed that there was a significant decrease in Analgesia Nociception Index after a tetanic stimulation while hemodynamic and BIS parameters did not change, suggesting that the Analgesia Nociception Index may perform better than traditional hemodynamic parameters at reflecting noxious stimulation. Analgesia Nociception Index significantly changed at lower, but not at higher, remifentanil concentrations.

Electromyographic assessment of blink reflex throughout the transition from responsiveness to unresponsiveness during induction with propofol and remifentanil.

General anesthesia is a reversible drug-induced state of altered arousal characterized by loss of responsiveness due to brainstem inactivation. Precise identification of the moment in which responsiveness is lost during the induction of general anesthesia is extremely important to provide information regarding an individual's anesthetic requirements and help intraoperative drug titration. To characterize the transition from responsiveness to unresponsiveness more objectively, we studied neurophysiologic-derived parameters of electromyographic records of electrically evoked blink reflex as a means of identifying the precise moment of loss of responsiveness. Twenty-five patients received a slow infusion of propofol until loss of corneal reflex while successive blink reflexes were elicited and recorded every 6 s. The level of anesthesia was assessed using an adapted version of the Richmond Agitation-Sedation Scale. Different variables of the blink reflex components were calculated and compared to the adapted version of the Richmond Agitation-Sedation score and the estimated effect-site propofol concentration. Baselines of the blink reflex responses were similar to those in literature. After propofol infusion started, the most susceptible component of the blink reflex to propofol was R2 (EC50 = 1.358 (95% CI 1.321, 1.396) µg/mL) and the most resistant was R1 (EC50 = 3.025 (95% CI 2.960, 3.090) µg/mL). Most of the patients (24 out of 25) lost the R1 component when they were still responsive to shaking and shouting and corneal reflex could be elicited clinically (time = 102.48 ± 33.00 s). Habituation was present in R2 but not in R1. The R1 component of the blink reflex was found to have a strong correlation with the adapted version of the Richmond Agitation-Sedation Scale, with amplitude correlating better than areas (ρ = - 0.721 (0.123) versus ρ = - 0.688 (0.165)). We found a strong correlation between the R1 component with the estimated propofol effect-site concentration, with amplitude correlating better than areas (ρ = - 0.838 (0.113) versus ρ = - 0.823 (0.153)) and between the clinical scale and the propofol concentration (ρ = 0.856 (0.060)). The area and amplitude of the R1 component showed to be indicators of predicting different levels of anesthesia (Pk = 0.672 (0.183) versus Pk = 0.709 (0.134)) and these are connected to the propofol concentrations (Pk = 0.593 (0.10)). Our results suggest that electrically evoked blink reflex could be used during the induction of anesthesia as a surrogate of the Richmond Agitation-Sedation Scale to provide an objective endpoint as far as a - 4. At this point, at the moment of loss of R1, the propofol infusion may be stopped, as overshooting increases slightly the effect-site concentration afterward and eventually reaching loss of responsiveness. If the desired target is not achieved, the infusion can then be resumed.

Foreseeing postoperative pain in neurosurgical patients: pupillometry predicts postoperative pain ratings-an observational study.

Pupillary reflex dilation (PRD) is triggered by noxious stimuli and diminished by opioid administration. In the postoperative period, PRD has been shown to be correlated with pain reporting and a useful tool to guide opioid administration. In this study we assessed whether pupillary measurements taken before extubation were related with the patient's reported pain in the Post-Anesthesia Care Unit (PACU) using the Numerical Rating Scale (NRS). Our objective was to evaluate the correlation of PRD and pupillary variables measured intraoperatively with postoperative pain under the same opioid concentration. This was a prospective observational study of 26 neurosurgical patients undergoing general anesthesia exclusively with propofol and remifentanil. A portable infrared pupillometer was used to provide an objective measure of pupil size and PRD (using the Pupillary Pain Index) before extubation. Pain ratings were obtained from patients after recovery of consciousness, while remifentanil was maintained at 2 ng/mL. A significant correlation was observed between NRS scores and pre-extubation PPI (rS = 0.62; P = 0.002), as well as between NRS scores and pupil diameter before tetanic stimulation PPI (rS = 0.56, P = 0.006). We also found a negative correlation between pupil diameter and age (rS = - 0.42, P = 0.04). The statistically significant correlation between pre-extubation PPI scores and NRS scores, as well as between the pupillary diameter before tetanic stimulation and NRS scores suggest the possibility of titrating analgesia at the end of the intraoperative period based on individual responses. This could allow clinicians to identify the ideal remifentanil concentration for the postoperative period.

Clinical outcomes of aortic arch hybrid repair in a real-world single-center experience.

OBJECTIVE: Aortic arch aneurysmal disease remains a therapeutic challenge. For patients unsuitable for standard open surgery, hybrid repair with debranching of the supra-aortic arteries followed by thoracic endovascular grafting has been shown to be an effective solution. The aim of this study was to report the clinical outcomes of a single-institution experience using hybrid aortic arch repair. METHODS: The cases of all consecutive patients submitted to hybrid aortic arch repair between January 2010 and June 2018 were prospectively collected and retrospectively analyzed. The outcomes of the study were 30-day mortality, perioperative complications, 2-year survival, endoleak, and reintervention rates. RESULTS: A total of 35 patients with a median age of 71 years (interquartile range, 62-77 years) were submitted to hybrid aortic arch repair, with a median follow-up of 26.9 months (interquartile range, 2.4-63.6 months). Ten procedures (28.6%) were performed urgently for contained rupture. The most common etiology was degenerative (n = 14 [40.0%]). The proximal landing zones according to the Ishimaru classification were zone 2 in 20 patients (57.1%), zone 1 in 12 patients (34.3%), and zone 0 in 3 patients (8.6%). Early endoleaks were observed in six patients (17.1%), equally distributed between type I and type II. Late endoleaks were identified in 4 of 24 patients (16.7%; type I, n = 2 [8.3%]; type II, n = 1 [4.2%]; and type III, n = 1 [4.2%]). Thirty-day mortality rate was 14.3% (n = 5) with an early death rate of 8.7% (2/23) in elective cases and 30.0% (3/10) in urgent cases (odds ratio [OR], 4.93; confidence interval [CI], 0.68-35.67; P = .128). Except in one patient, 30-day mortality was associated with landing zone 0 or zone 1 (26.7% vs 5.0%; OR, 6.91; CI, 0.68-69.86; P = .141). Three patients (8.6%) suffered a postoperative stroke, and no episodes of spinal cord ischemia were observed. Two-year survival rate was 67.8% (CI, 49.4%-80.8%). Survival rates were significantly lower with increasing age (hazard ratio [HR], 1.10; CI, 1.03-1.18; P = .004), urgent procedure (HR, 4.80; CI, 1.56-14.80; P = .003), zone 0 or zone 1 (HR, 6.34; CI, 1.73-23.18; P = .001), presence of arrhythmia (HR, 3.76; CI, 1.22-11.62; P = .013), and cerebrovascular disease (HR, 4.12; CI, 1.38-12.35; P = .006). A multivariate analysis identified age (HR, 1.11; P = .047) and zone 0 or zone 1 (HR, 4.93; P = .033) as the only predictors for overall mortality. CONCLUSIONS: Hybrid aortic arch repair seems to be an alternative for higher risk patients not suitable for open repair, but selection of patients is crucial and may benefit from further refinement. In this study, worse outcomes were seen in older patients and those who required more proximal landing zones.

Clinical aspects and present challenges of the seat belt aorta.

OBJECTIVE: Seat belt aorta is rare and difficult to manage. The lack of data and follow-up increases the complexity of treating such patients. We aimed to create a decision algorithm by reviewing our current experience and analyzing the presentation and management of our patients. METHODS: We performed a descriptive case series based on retrospective analysis of all consecutive patients admitted with the diagnosis of seat belt aorta from 2008 to 2018. Seat belt aorta was defined as any blunt abdominal aortic lesion resulting from a seat belt compression mechanism after a car accident. RESULTS: Nine consecutive patients were admitted with the diagnosis of seat belt aorta, all of whom developed lesions in the infrarenal aorta. Eight patients were assessed in the acute phase and one patient presented with late-onset symptoms. Associated injuries were present in all acute patients, and seat belt sign and small bowel injury were present in 88%. One patient presented with a small intimal tear and was treated conservatively. All other patients diagnosed with large intimal flaps (seven patients) and pseudoaneurysm (one patient) underwent open repair in five cases and endovascular repair in three cases. In-hospital mortality for the acute cases was 38%, with no mortality seen during follow-up. Two patients submitted to endovascular repair required reinterventions. CONCLUSIONS: Seat belt aorta is a deadly condition, frequently associated with blunt thoracoabdominal trauma with concomitant injuries; the presence of a seat belt sign or lower limb ischemia must lead to a high diagnostic suspicion. Management must take into account the other concomitant injuries. Follow-up is crucial as most patients are young; they may develop complications and subsequently require further intervention.

Performance of blink reflex in patients during anesthesia induction with propofol and remifentanil: prediction probabilities and multinomial logistic analysis.

BACKGROUND: The amount of propofol needed to induce loss of responsiveness varied widely among patients, and they usually required less than the initial dose recommended by the drug package inserts. Identifying precisely the moment of loss of responsiveness will determine the amount of propofol each patient needs. Currently, methods to decide the exact moment of loss of responsiveness are based on subjective analysis, and the monitors that use objective methods fail in precision. Based on previous studies, we believe that the blink reflex can be useful to characterize, more objectively, the transition from responsiveness to unresponsiveness. The purpose of this study is to investigate the relation between the electrically evoked blink reflex and the level of sedation/anesthesia measured with an adapted version of the Richmond Agitation-Sedation Scale, during the induction phase of general anesthesia with propofol and remifentanil. Adding the blink reflex to other variables may allow a more objective assessment of the exact moment of loss of responsiveness and a more personalized approach to anesthesia induction. RESULTS: The electromyographic-derived features proved to be good predictors to estimate the different levels of sedation/anesthesia. The results of the multinomial analysis showed a reasonable performance of the model, explaining almost 70% of the adapted Richmond Agitation-Sedation Scale variance. The overall predictive accuracy for the model was 73.6%, suggesting that it is useful to predict loss of responsiveness. CONCLUSIONS: Our developed model was based on the information of the electromyographic-derived features from the blink reflex responses. It was able to predict the drug effect in patients undergoing general anesthesia, which can be helpful for the anesthesiologists to reduce the overwhelming variability observed between patients and avoid many cases of overdosing and associated risks. Despite this, future research is needed to account for variabilities in the clinical response of the patients and with the interactions between propofol and remifentanil. Nevertheless, a method that could allow for an automatic prediction/detection of loss of responsiveness is a step forward for personalized medicine.

An Original Bailout Solution for Renal Artery Dissection after Fenestrated/Branched EVAR.

BACKGROUND: Renal artery (RA) dissection may occur during endovascular treatment of thoracoabdominal aneurysms. The aim of this paper is to report the use of kissing coronary stents in the renal bifurcation as a bailout solution for dissection after fenestraded/branched endovascular aortic repair (F/B-EVAR). METHODS/RESULTS: A 73-year-old male with an asymptomatic Crawford type 4 thoracoabdominal aneurysm and a concomitant right common iliac artery aneurysm was proposed for endovascular repair, consisting of thoracic endovascular aortic repair plus custom-made device F/B-EVAR, followed by staged bifurcated EVAR plus right-sided IBD. In the control angiogram of the first procedure, a distal occlusion of the left renal artery was observed and attributed to iatrogenic dissection. The 6F sheath was reintroduced and the two main branches of the RA were catheterized with 0.014 wires. Then, two coronary drug-eluting stents were used for a kissing stenting technique with good angiographic and clinical results. As planned, one week later the patient underwent an uneventful second stage procedure. Follow-up CTA at 1 year showed normal patency of the renal stents as well as aneurysm shrinking and no signs of endoleak. CONCLUSIONS: In the reported case, the use of coronary stents was a safe and long-lasting solution to rescue an iatrogenic renal artery dissection during F/B-EVAR.

A single-center experience in the eversion femoral endarterectomy.

OBJECTIVES: Endarterectomy is the treatment of choice for arterial occlusive disease of the femoral bifurcation. Longitudinal arteriotomy and prosthetic patch angioplasty is the standard technique but, due to the increasing concerns with prosthetic-related infections and multidrug-resistant pathogens our group adopted an alternative approach. We present our experience with eversion femoral endarterectomy. METHODS: All patients submitted to eversion femoral endarterectomy in a single institution during 2016-2019 were retrospectively analyzed. Patient demographics, surgical data, and complications were captured from medical records. RESULTS: Nineteen patients, 84.2% male and a median age of 67 years (IQR 62-78) were submitted to eversion femoral endarterectomy with a median follow-up of 180 days (IQR 71-395). Seventeen (89.4%) patients were treated for chronic limb ischemia and the other two were submitted to femoral endarterectomy during endovascular aortic aneurysm repair. Most of the patients had smoking history (84.2%), followed by hypertension (68.4%), dyslipidemia (63.2%), coronary heart disease (29.4%), and diabetes (26.3%). Only 3 patients (15.8%) were submitted exclusively to endarterectomy, 13 (68.4%) were submitted to endarterectomy as an adjuvant for peripheral endovascular treatment, 2 (10.5%) as a concomitant procedure to endovascular repair of aortic aneurysm, and 1 (5.3%) was complemented with thrombectomy of the femoro-popliteal sector. Primary patency rates were 100% and 87.5% (CI (38.7-98.1)) at 6 and 12 months, respectively. Primary-assisted and secondary patency rates were 100%. The 30-day mortality rate was 5.3% (n = 1) and complication rate 10.5% (n = 2). One patient complicated with acute renal disease related to rhabdomyolysis. Another patient developed a wound-related hematoma treated with surgical drainage, but died three days after consequent to ischemia-reperfusion injury. CONCLUSIONS: Eversion femoral endarterectomy is a safe and feasible technique, with good patency results and respecting the concept of leaving nothing behind. A careful control of the proximal and distal endpoints is essential for the success of the technique.

Pharmacodynamic modelling of the effect of remifentanil using the Pupillary Pain Index.

Using a targeted controlled infusion of remifentanil during total intravenous anesthesia, we investigated the effect-site concentrations of remifentanil that correlate with different values of the Pupillary Pain Index and which concentrations were necessary for achieving a Pupillary Pain Index ≤ 4 and its usefulness in titrating opioids. The Pupillary Pain Index was measured in 54 patients prior to surgery under different remifentanil effect-site concentrations and subsequently modeled. One hundred and twenty-eight measurements were taken at different remifentanil concentrations while titrating propofol for a similar depth of hypnosis using a BIS monitor. Our modeled Hill equation revealed a remifentanil of 2.96 ng/mL for a PPI of 4, and the probability model a Ce of 3.22 ng/mL for the probability of 50% of patients achieving a PPI score ≤ 4. For the probability of 80% of patients achieving a PPI score ≤ 4 the Ce of remifentanil was 4.39 ng/mL. We conclude that concentrations of remifentanil that have been shown to suppress movement in response to noxious stimulation correspond to a Pupillary Pain Index ≤ 4.

Hybrid Surgery in Lower Limb Revascularization: A Real-World Experience from a Single Center.

BACKGROUND: Through the association of endovascular and open procedures, hybrid surgery for lower limb revascularization allows the treatment of multilevel occlusive disease with a lower risk when compared to extensive open interventions. The aim of this study is to evaluate the immediate and midterm clinical outcomes of hybrid techniques for lower limb revascularization in a cohort of patients with multilevel arterial disease. METHODS: Data from elective procedures between 2012 and 2017 were retrospectively collected regarding hybrid lower limb revascularization procedures. The outcomes of the study were categorical clinical improvement, patency rates, major amputation rates, and mortality. RESULTS: A total of 81 patients, 89 limbs, with a median age of 69 years (interquartile range [IQR] 61-73) were submitted to hybrid lower limb revascularization, with a median follow-up of 10.7 months (IQR 2.5-25.1). Treatment indications were chronic limb-threatening ischemia in 80.9% of the cases (rest pain in 18.0% and tissue loss in 62.9%). One-year primary, primary-assisted, and secondary patency rates were 78.28% (95% confidence interval [CI] 65.20-86.92), 85.12% (95% CI 72.96-92.09), and 90.19% (95% CI 79.13-95.54), respectively. Overall categorical clinical improvement was observed in 56.2%. Major amputation and mortality rates were 14.6% and 16.0%, respectively. Multilevel Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) C or D and stage IV Leriche-Fontaine classification were strongly associated with decreased categorical clinical improvement (adjusted odds ratio [aOR] 0.08, P < 0.0001 and aOR 0.25, P = 0.013, respectively). Multilevel TASC C or D was also related to higher amputation rates, contrary to clinical presentation (adjusted hazard ratio [aHR] 11.37, P = 0.002 and aHR 4.70, P = 0.091, respectively). Primary-assisted and secondary patency rates were associated with higher categorical clinical improvement (aOR 4.30, P = 0.036 and aOR 7.36, P = 0.021, respectively) and decreased major amputation rates (aHR 0.11, P = 0.003 and aHR 0.09, P = 0.001, respectively) but were not related to multilevel TASC and Leriche-Fontaine classifications. CONCLUSIONS: The present study reports a real-world experience with a large proportion of patients with chronic limb-threatening ischemia. Hybrid interventions for lower limb revascularization revealed to be a potential approach for patients with complex arterial disease that would beneficiate from less invasive procedures.

Rediscovery of Leptopanchax splendens (Cyprinodontiformes: Aplocheilidae): a seasonal killifish from the Atlantic Forest of south-eastern Brazil that was recently considered extinct.

A recent collection of the seasonal killifish found Leptopanchax splendens c. 5 km from the type locality, 74 years after its last record. The species was historically common in its type locality, the Estrela River basin in south-eastern Brazil, until 1950, after which it was not encountered and thought to have become extinct due to widespread deforestation and urbanization in the region. Despite the rediscovery, this study finds that other recently published reports of L. splendens are misidentifications.

Molecular phylogeny and timing of diversification in South American Cynolebiini seasonal killifishes.

The rich biological diversity of South America has motivated a series of studies associating evolution of endemic taxa with the dramatic geologic and climatic changes that occurred during the Cainozoic. The organism here studied is the killifish tribe Cynolebiini, a group of seasonal fishes uniquely inhabiting temporary pools formed during the rainy seasons. The Cynolebiini are found in open vegetation areas inserted in the main tropical and subtropical South American phytogeographical regions east of the Andes. Here, we present the first molecular phylogeny sampling all the eight genera of the Cynolebiini, using fragments of two mitochondrial and four nuclear genes for 35 species of Cynolebiini plus 19 species as outgroups. The dataset, 4448bp, was analysed under Bayesian and maximum likelihood approaches, providing a relatively well solved tree, which retrieves high support values for the Cynolebiini and most included clades. The resulting tree was used to estimate the time of divergence in included lineages using two cyprinodontiform fossils to calibrate the tree. We further investigated historical biogeography through the likelihood-based DEC model. Our estimates indicate that divergence between the clades comprising New World and Old World aplocheiloids occurred during the Eocene, about 50Mya, much more recent than the Gondwanan fragmentation scenario assumed in previous studies. This estimation is nearly synchronous to estimated splits involving other South American and African vertebrate clades, which have been explained by transoceanic dispersal through an ancient Atlantic island chain during the Palaeogene. We estimate that Cynolebiini split from its sister group Cynopoecilini in the Oligocene, about 25Mya and that Cynolebiini started to diversify giving origin to the present genera during the Miocene, about 20-14Mya. The Cynolebiini had an ancestral origin in the Atlantic Forest and probably were not present in the open vegetation formations of central and northeastern South America until the Middle Miocene, when expansion of dry open vegetation was favoured by cool temperatures and strike seasonality. Initial splitting between the genera Cynolebias and Simpsonichthys during the Miocene (about 14Mya) is attributed to the uplift of the Central Brazilian Plateau.

A novel multivariate STeady-state index during general ANesthesia (STAN).

The assessment of the adequacy of general anesthesia for surgery, namely the nociception/anti-nociception balance, has received wide attention from the scientific community. Monitoring systems based on the frontal EEG/EMG, or autonomic state reactions (e.g. heart rate and blood pressure) have been developed aiming to objectively assess this balance. In this study a new multivariate indicator of patients' steady-state during anesthesia (STAN) is proposed, based on wavelet analysis of signals linked to noxious activation. A clinical protocol was designed to analyze precise noxious stimuli (laryngoscopy/intubation, tetanic, and incision), under three different analgesic doses; patients were randomized to receive either remifentanil 2.0, 3.0 or 4.0 ng/ml. ECG, PPG, BP, BIS, EMG and [Formula: see text] were continuously recorded. ECG, PPG and BP were processed to extract beat-to-beat information, and [Formula: see text] curve used to estimate the respiration rate. A combined steady-state index based on wavelet analysis of these variables, was applied and compared between the three study groups and stimuli (Wilcoxon signed ranks, Kruskal-Wallis and Mann-Whitney tests). Following institutional approval and signing the informed consent thirty four patients were enrolled in this study (3 excluded due to signal loss during data collection). The BIS index of the EEG, frontal EMG, heart rate, BP, and PPG wave amplitude changed in response to different noxious stimuli. Laryngoscopy/intubation was the stimulus with the more pronounced response [Formula: see text]. These variables were used in the construction of the combined index STAN; STAN responded adequately to noxious stimuli, with a more pronounced response to laryngoscopy/intubation (18.5-43.1 %, [Formula: see text]), and the attenuation provided by the analgesic, detecting steady-state periods in the different physiological signals analyzed (approximately 50 % of the total study time). A new multivariate approach for the assessment of the patient steady-state during general anesthesia was developed. The proposed wavelet based multivariate index responds adequately to different noxious stimuli, and attenuation provided by the analgesic in a dose-dependent manner for each stimulus analyzed in this study.

Molecular phylogeny and evolution of internal fertilization in South American seasonal cynopoeciline killifishes.

Internal fertilization is a widespread mode of reproduction in chondrichthyans and tetrapods, but uncommon in actinopterygian fishes. In killifishes of the suborder Aplocheiloidei, internal fertilization is restricted to two genera, Campellolebias and Cynopoecilus, both containing species adapted to life in seasonal pools of subtropical South America and exhibiting elaborated inseminating structures. Phylogenetic studies involving these genera are scarce and limited to morphological characters and fragments of mitochondrial DNA sequences available for a few taxa, providing incongruent results and thus impeding hypotheses on the evolution of insemination and related morphological traits. We analyzed three nuclear loci (GLYT1, ENC1, Rho) for 13 aplocheiloid taxa obtaining the first well-supported phylogeny for cynopoecilines, thus providing a significant background to interpret evolutionary changes within the group. Like in killifishes of the suborder Cyprinodontoidei, the evolution of internal fertilization in aplocheiloids is associated with deep changes in the structure of male anal fin. The phylogenetic analyses indicate that internal fertilization corresponds to a single evolutionary event during the evolution of aplocheiloid killifishes. The analyses also indicate that male specialized muscle characters, comprising a muscular ejaculatory pump in the urogenital region and hypertrophied inclinatores and depressores anales, arose in the ancestor of the clade comprising Campellolebias and Cynopoecilus. On the other hand, anal fin specialized structures including the male inseminating tube of Campellolebias and the male inseminating fan of Cynopoecilus evolved independently in each genus.

Retrieval of a Broken Dental Needle Close to the Facial Artery After Cervical Migration.

Use of imaging tools like digital C-arm, tridimensional tomography, and navigational surgery has proven its value to the surgical removal of broken needles. A 32-year-old patient was referred for evaluation of a fractured needle during inferior alveolar nerve block attempt few days before. The patient complained of a pricking sensation at the injured area while moving the neck. A contrasted computed tomography was performed for further evaluation of the needle toward the vascular network of the neck, showing a close location by the left facial artery, parallel to the styloid process of the temporal bone. The needle was then released from the underlying tissues and retrieved. Although considered a rare intercurrence, there are still reports of breaking needles during dental anesthesia. Such reports are almost always related to inferior alveolar nerve blocks, associated with the use of short, thin needles, and after multiple bending movements before the insertion of the needle in the tissues. Accurate image examinations such as contrasted computed tomography are of great importance for planning the surgical removal, especially in patients of migration next to important vessels of the neck.

Severe Edema After Sclerotherapy of Labial Hemangioma With Ethamolin Oleate in a Young Child.

Adverse reactions related to ethanolamine oleate (EO) include pain during injection, redness, inflammation, tissue necrosis, and allergic reaction. The authors report a patient of exuberant facial edema after the injection of EO used in sclerotherapy of lip hemangioma in a child. A 9-year-old boy was referred to authors' oral and maxillofacial surgery unit to treat a vascular lesion of the upper lip. The lesion has causing enlargement of the middle area of the upper lip, being sessile and resilient by palpation. It was decided to employ sclerotherapy aiming to reduce the size for posterior surgical excision of the residual lesion. The day after the injection, the patient presented intense edema limited to the upper lip, complaining of mild pain. Although side effects reported of EO injection are mild and with almost no clinical significance, major complications like anaphylaxis and severe edema can occur, such in the patient here presented.

Effect of propofol and remifentanil on a somatosensory evoked potential indicator of pain perception intensity in volunteers.

Somatosensory evoked potentials (SEPs) have been linked to noxious activation and stimulus intensity. In this exploratory study we investigated the impact of anaesthetic drugs on SEPs and pain ratings, to assess their applicability as an objective measure of the nociception/anti-nociception balance. Following institutional approval and written informed consent, 10 healthy adult volunteers were enrolled (29.5 ± 9.1 years, 63.0 ± 8.9 kg and 171.4 ± 7.2). Median nerve electrical stimulation was adjusted according to volunteers' sensitive, motor and painful thresholds (PT). Baseline SEPs were registered, and remifentanil and propofol administered using a stair scheme TCI. For each drug combination a 1.3×PT stimulus was administered, and volunteers evaluated pain intensity in a numerical rating scale (0-10). SEPs' amplitudes and latencies were normalized by the baseline values, reducing volunteers' intervariability. Stimulation currents varied between 6-52 mA (1.3×PT) and pain ratings between 0 and 9. Cortical SEPs latencies were decreased for higher stimulus intensities (P < 0.01), accompanied by increased pain ratings (P < 0.01). An individually adjusted/normalized ratio based on cortical SEPs amplitude and interpeak latency is proposed([Formula: see text]): [Formula: see text] and NSR were significantly correlated in three out of nine subjects, and [Formula: see text] and remifentanil Ce were significantly correlated in two (low number of evaluation points). [Formula: see text] was shown to decrease with increasing doses of propofol and remifentanil (P < 0.05). The proposed metric was depressed by anaesthetics and reflected pain evaluations. Further research is necessary to increase the number of volunteers and drugs' combination, to assess its applicability during surgically adequate anesthetic leves.