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INTRODUCTION/OBJECTIVES: Thin and hypokinetic myocardial segments (THyMS) represent adverse ventricular (LV) remodeling in human hypertrophic cardiomyopathy. We describe the echocardiographic features and outcome in cats with THyMS, and in a subpopulation, the echocardiographic phenotype before LV wall thinning was detected (pre-THyMS). ANIMALS: Eighty client-owned cats. MATERIALS AND METHODS: Retrospective multicenter study. Clinical records were searched for cats with THyMS, defined as LV segment(s) with end-diastolic wall thickness (LVWT) 4 mm and normal wall motion. When available, echocardiograms pre-THyMS were assessed. Survival time was defined as time from first presentation with THyMS to death. RESULTS: Mean thickest LV wall segment (MaxLVWT) was 6.1 mm (95% CI 5.8-6.4 mm) and thinnest (MinLVWT) was 1.7 mm (95% CI 1.6-1.9 mm). The LV free wall was affected in 74%, apex in 13% and septum in 5%. Most cats (85%) presented with heart failure and/or arterial thromboembolism. Median circulating troponin I concentration was 1.4 ng/mL ([range 0.07-180 ng/mL]). Prior echocardiography results were available for 13/80 cats, a mean of 2.5 years pre-THyMS. In segments subsequently undergoing thinning, initial MaxLVWT measured 6.7 mm (95% CI 5.8-7.7 mm) vs. 1.9 mm (95% CI 1.5-2.4 mm) at last echocardiogram (P

BackgroundEvidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery.MethodsA systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations.ResultsAnalysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92).ConclusionsBased on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes.Recommendation: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Acute compartment syndrome (ACS) is a potential orthopedic emergency that leads, without prompt diagnosis and immediate treatment with surgical fasciotomy, to permanent disability. The role of regional anesthesia (RA) for analgesia in patients at risk for ACS remains unjustifiably controversial. This critical review aims to improve the perception of the published literature to answer the question, whether RA techniques actually delay or may even help to hasten the diagnosis of ACS. According to literature, peripheral RA alone does not delay ACS diagnosis and surgical treatment. Only in 4 clinical cases, epidural analgesia was associated with delayed ACS diagnosis.

Study objectives The aim of this study was to assess the impact of intravenous general anesthesia and controlled hypotension on cerebral saturation (rScO2), cerebral blood flow measured as middle cerebral artery blood flow velocity (Vmax MCA) and neurobehavioral outcome in patients scheduled for shoulder surgery in beach chair position. Design Prospective, assessor-blinded observational study. Setting University hospital, shoulder surgery operating room. Patients Forty ASA I-II patients scheduled for shoulder surgery in beach chair position and controlled hypotension. Interventions Neurological and neurobehavioral tests were performed prior and the day after surgery. The baseline data for near-infrared spectroscopy, bispectral index, cerebral blood flow, PaCO2 and invasive blood pressure (radial artery) were taken prior anesthesia and after anesthesia induction, after beach chair positioning and all 20 min after surgery start until discharge of the patient. Measurements Neurological and neurobehavioral tests, cerebral saturation (rScO2) using near-infrared spectroscopy, BIS, cerebral blood flow using Doppler of the middle cerebral artery (Vmax MCA), PaCO2 and invasive blood pressure assessed at heart and at the external acoustic meatus level. Main results The incidence of cerebral desaturation events (CDEs) was 25%. The blood pressure drop 5 min after beach chair position measured at the acoustic meatus level in the CDE group was higher compared to patients without CDEs (p = 0.009) as was the rScO2 (p = 0.039) and the Vmax MCA (p = 0.002). There were no neurological deficits but patients with CDEs showed a greater negative impact on neurobehavioral tests 24 h after surgery compared to patients without CDEs (p = 0.001). Conclusions In ASA I-II patients intravenous general anesthesia and controlled hypotension in the beach chair position affects cerebral blood flow and cerebral oxygenation with impact on the neurobehavioral outcome.

BACKGROUND Diclofenac and other NSAIDs are routinely used in the postoperative period. Their effect on fracture healing remains unclear and controversial. OBJECTIVE The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of diclofenac on human osteoblasts. DESIGN Laboratory in vitro study. SETTING Institute of Physiology, Zurich, Center for Integrative Human Physiology, University of Zurich. MATERIALS Monolayers of human osteoblasts. INTERVENTIONS Exposure of human osteoblast monolayers to several concentrations of diclofenac, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES Cell count, cell viability, cell proliferation and apoptosis. RESULTS A concentration-mediated, time and exposure dependent cytotoxic effect of diclofenac-mediated apoptosis was observed. Stimulated inflammatory conditions seemed to reduce toxic effects. CONCLUSION Cytotoxic effects of diclofenac are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to diclofenac cytotoxicity, especially in the presence of higher concentration and longer exposure time.

Postoperative opioid analgesia may cause respiratory depression. We assessed whether following total hip arthroplasty, placebo-adjusted reductions in morphine consumption at 48 hours with parecoxib (47.0%), propacetamol (35.1%) or parecoxib plus propacetamol (67.9%) translated into a reduction in hypoxemic events.This was a post hoc analysis of a randomized, placebo-controlled, noninferiority study. Patients were randomly assigned to receive intravenous parecoxib (40 mg twice daily), propacetamol (2 g 4 times daily), parecoxib plus propacetamol (40 mg twice daily + 2 g 4 times daily) or placebo. Dose, date and time of morphine administration via patient-controlled analgesia were monitored throughout the study. In patients not receiving supplemental oxygen, peripheral blood oxygenation was assessed continuously for 48 hours after surgery. Hypoxemia was defined as peripheral oxygen saturation less than 90%. The times and oximeter readings of hypoxemic events were recorded. Pearson correlation coefficient was used to assess for correlations between cumulative morphine consumption at 48 hours and mean number of hypoxemic events.A significantly smaller proportion of patients who received the combined treatment with parecoxib and propacetamol had hypoxemia versus placebo (2.8% v. 13.2%, p0.05), and the mean number of hypoxemic events was significantly smaller for parecoxib (0.12), propacetamol (0.06) and parecoxib plus propacetamol (0.03) versus placebo (0.36; all p0.05). There was no correlation between the reduction in cumulative morphine consumption at 48 hours and the mean number of hypoxemic events in any treatment group (all p0.1).Following total hip arthroplasty, a greater than 70% reduction in morphine consumption may be necessary to translate into a corresponding reduction in hypoxemic events.L’utilisation d’analgésiques opioïdes en période postopératoire peut provoquer une dépression respiratoire. Nous avons voulu déterminer si, après une arthroplastie totale de la hanche, une réduction de la consommation de morphine à 48 heures par l’administration de parécoxib (47,0 %), de propacétamol (35,1 %) ou d’une combinaison des deux (67,9 %) — avec ajustement selon un groupe placebo — se traduirait par une réduction du nombre d’épisodes d’hypoxémie.Nous avons effectué une analyse post hoc d’une étude randomisée de non-infériorité avec témoins sous placebo. Après une répartition aléatoire, chaque patient a reçu par intraveineuse du parécoxib (40 mg 2 fois par jour), du propacétamol (2 g 4 fois par jour), une combinaison de parécoxib et de propacétamol (40 mg 2 fois par jour + 2 g 4 fois par jour) ou un placebo. Tout au long de l’étude, la dose, la date et le moment de l’administration de morphine contrôlée par le patient ont été notés. Chez les patients qui ne recevaient pas d’oxygène d’appoint, la saturation périphérique en oxygène a été surveillée de manière continue pendant les 48 heures suivant l’opération. L’hypoxémie a été définie comme une saturation inférieure à 90 %. Le moment et les données d’oxymétrie ont été notés pour chaque épisode d’hypoxémie. Le coefficient de corrélation de Pearson a été utilisé pour évaluer la présence de corrélations entre la consommation cumulative de morphine durant les premières 48 heures et le nombre moyen d’épisodes d’hypoxémie.Une proportion significativement plus faible de patients ayant reçu le traitement combiné de parécoxib et de propacétamol ont connu des épisodes d’hypoxémie, comparativement aux patients qui avaient reçu le placebo (2,8 % c. 13,2 %, p0,05), et le nombre moyen d'épisodes d'hypoxémie était significativement plus faible dans le groupe ayant reçu du parécoxib (0,12), du propacétamol (0,06) ou une combinaison de parécoxib et de propacétamol (0,03), par rapport au groupe placebo (0,36, p0,05 pour tous). Aucune corrélation n'a été observée entre la réduction de la quantité totale de morphine consommée à 48 heures et le nombre moyen d'épisodes d'hypoxémie pour tous les groupes (p0,1 pour tous).Après une arthroplastie totale de la hanche, une réduction de la consommation de morphine de plus de 70 % pourrait être nécessaire pour obtenir une réduction correspondante du nombre d’épisodes d’hypoxémie.

An infraclavicular catheter is a very efficient technique to provide excellent perioperative anesthesia/analgesia for upper limb surgery. However, complications can occur and are dependent on the technique used. We report the inadvertent placement of an infraclavicular catheter in the interscalene region when an ultrasound-guided infraclavicular catheter was threaded cranially. We proposed some strategies to avoid the occurrence of complications when performing this block.

Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD., The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.

Objective To propose some key steps to facilitate the process of creating mental health smartphone applications (apps). Methods Brief presentation of the potential interest of apps and proposition of key steps for the creation of apps. The paper is based on a narrative review, a testimonial experience and some expert works. Results Apps have ubiquitous features that are particularly appealing for the mental health field. Potentially connected to multiple technologies, mobile and available at all times, they allow great design flexibility. In order to increase the chances of effectiveness and good dissemination of a given app, 9 principles could usefully guide the design of apps, in particular a good integration of end users around well-defined target objectives during the entire process of creating such tools. Conclusion The proposed key steps could facilitate the process of creating mental health apps.

Background: The metastatic potential of breast cancer cells has been strongly associated with overexpression of the chemokine CXCL12 and the activity of its receptor CXCR4. Lidocaine, a local anaesthetic that can be used during breast cancer excision, inhibits the growth, invasion, and migration of cancer cells. We therefore investigated, in a breast cancer cell line, whether lidocaine can modulate CXCL12-induced responses. Methods: Intracellular calcium, cytoskeleton remodelling, and cell migration were assessed in vitro in MDA-MB-231 cells, a human breast cancer epithelial cell line, after exposure to lidocaine (10 μM or 100 μM). Results: Lidocaine (10 or 100 μM) significantly inhibited CXCR4 signalling, resulting in reduced calcium release (Fluo 340 nm/380 nm, 0.76 mean difference, p

The adult population in Chile has a high prevalence of dental caries and non-functional dentition. Fifteen years after the Health Reform, aimed to reduce health inequalities, it is necessary to analyse changes in social inequalities in oral health in Chilean adults. METHODS A secondary analysis of data from 2003 and 2016-2017 National Health Surveys (NHS) in Chile was performed on seven oral health outcomes in adults: prevalence of untreated caries, prevalence of severe untreated caries, number of teeth with untreated caries, prevalence of functional dentition, prevalence of edentulism, number of remaining natural teeth and utilization of dental services. Inequalities were measured with the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII) by education level. RESULTS A decrease of caries inequalities measured with SII was observed from 2003 to 2016-17 NHS but an increase of remaining teeth inequalities was measured. The SII of the remaining teeth increased from 6.6 [95% CI = 5.0, 8.2] in 2003 to 8.8 [95% CI = 7.3, 10.3] in 2016-17. The SII of functional dentition by education increased from 29.0 [95% CI = 22.0, 36.0] in 2003 to 38.8 [95% CI = 32.6, 45.0]) in 2016-17. The utilization of dental services ≤1 year was the only outcome that showed a decrease in absolute and relative inequality, the SII was 33.9 [95% CI = 23.3, 45.6] in 2003 and 26.2 [95% CI = 16.6, 35.8] in 2016-17 and the RII decreased from 2.5 [95% CI = 1.7, 3.3] in 2003 to RII = 1.8 [95% CI = 1.4, 2.3] in 2016-17. CONCLUSION The increase of tooth loss inequalities in contrast to the decrease of inequalities in dental services utilization show the need to re-evaluate the current dental programmes for adults in Chile. This may include establishing a stronger oral health promotion strategy and greater dental treatment coverage focusing on avoiding tooth extractions in vulnerable social groups.

Shoulder surgery in the beach chair position is routinely performed, and central neurological events are rare but potentially devastating. We present a patient with transient neurological deficits after a sudden blood pressure drop with a simultaneous decrease of regional cerebral saturation values registered by cerebral oximetry. We reviewed published cases and proposed possible strategies to prevent the occurrence of similar complications in this context.

Cancer causes considerable suffering and 80% of advanced cancer patients experience moderate to severe pain. Surgical tumor excision remains a cornerstone of primary cancer treatment, but is also recognized as one of the greatest risk factors for metastatic spread. The perioperative period, characterized by the surgical stress response, pharmacologic-induced angiogenesis, and immunomodulation results in a physiologic environment that supports tumor spread and distant reimplantation.In the perioperative period, anesthesiologists may have a brief and uniquewindow of opportunity to modulate the unwanted consequences of the stressresponse on the immune system and minimize residual disease. This reviewdiscusses the current research on analgesic therapies and their impact ondisease progression, followed by an evidence-based evaluation of perioperativepain interventions and medications.

Three-dimensional (3D) printed models of anatomic structures offer an alternative to studying manufactured, “idealized” models or cadaveric specimens. The utility of 3D printed models of the heart for clinical veterinary students learning echocardiographic anatomy is unreported. This study aimed to assess the feasibility and utility of 3D printed models of the canine heart as a supplementary teaching aid in final-year vet students. We hypothesized that using 3D printed cardiac models would improve test scores and feedback when compared with a control group. Students ( n = 31) were randomized to use either a video guide to echocardiographic anatomy alongside 3D printed models (3DMs) or video only (VO). Prior to a self-directed learning session, students answered eight extended matching questions as a baseline knowledge assessment. They then undertook the learning session and provided feedback (Likert scores and free text). Students repeated the test within 1 to 3 days. Changes in test scores and feedback were compared between 3DM and VO groups, and between track and non-track rotation students. The 3DM group had increased test scores in the non-track subgroup. Track students’ test scores in the VO group increased, but not in the 3DM group. Students in the 3DM group had a higher completion rate, and more left free-text feedback. Feedback from 3DM was almost universally positive, and students believed more strongly that these should be used for future veterinary anatomy teaching. In conclusion, these pilot data suggest that 3D printed canine cardiac models are feasible to produce and represent an inclusive learning opportunity, promoting student engagement.

The aim of this work was to reidentify strains previously identified as Candida guilliermondii and Candida famata by conventional phenotypic methods conserved in a culture collection from Argentina using ribosomal DNA sequencing, ACT1 gene sequencing, and matrix-assisted laser desorption ionization - time of flight mass spectrometry (MALDI-TOF MS). In addition, we performed antifungal susceptibility tests of eight antifungal drugs commonly used in clinical treatment. We identified 68 isolates belonging to the Candida guilliermondii species complex (59 C. guilliermondii, 8 C. fermentati, and 1 Candida carpophila), 16 isolates belonging to the Candida famata species complex (8 C. famata, 6 Debaryomyces nepalensis, 1 Debaryomyces fabryi, and 1 Debaryomyces tyrocola). Although sequencing of ITS region was able to identify C. guilliermondii and D. nepalensis isolates, sequencing of ACT1 gene seems to be the most appropriate technique for differentiation between C. fermentati and C. carpophila and between members of the C. famata species complex others than D. nepalensis. MALDI-TOF MS has a good potential for the identification of these yeasts, particularly in clinical laboratories since is a rapid and easy to perform technique. Here, we report the first isolation of D. tyrocola from a human patient and the first isolation of D. nepalensis from lungs and blood of human patients. Finally, correct identification and determination of antifungal susceptibility of those closely related species could be a useful tool for clinicians to choose the most effective antifungal treatment.

Local anesthetics are used for performing various regional anesthesia techniques to provide intraoperative anesthesia and analgesia, as well as for the treatment of acute and chronic pain. Older medications such as lidocaine and bupivacaine as well as newer ones such as mepivacaine and ropivacaine are being used successfully for decades. Routes of administration include neuraxial, perineural, intravenous, various infiltrative approaches, topical, and transdermal. There are new innovations with the use of older local anesthetics in a novel manner, in addition to the development and use of new formulations. This chapter seeks to summarize the pharmacokinetics of local anesthetics and address the role of newer local anesthetics, as well as clinical implications, safety profiles, and the future of local anesthetic research. Finally, some clinical pearls are highlighted.

STUDY OBJECTIVE: Spinal anesthesia is well suited for day-care surgery, however a persisting motor block after surgery can delay discharge. Among the new drugs available, chloroprocaine has been associated with a short onset time, and motor block duration and a quicker discharge. However, it is not clear if those outcomes are clinically significantly superior compared to those associated with the use of low-dose hyperbaric bupivacaine. DESIGN: Aim of the study was to determine if spinal 2-chloroprocaine was superior to low-dose spinal bupivacaine regarding the following outcomes: onset time, block duration, time to ambulation and time to discharge. PATIENTS/INTERVENTIONS: We performed a systematic literature search of the last 30 years using PubMed Embase and the Cochrane Controlled Trials Register. We included only blinded, prospective trials comparing chloroprocaine with a low dose of bupivacaine for spinal anesthesia. Low dose bupivacaine was defined as a dose of 10 mg or less. Outcomes of interest were time to motor block regression (primary outcome), time to ambulation and time to discharge (secondary outcomes), as indirect indicators of a complete recovery after spinal anesthesia. MAIN RESULTS: Compared to a low dose bupivacaine, spinal 2-chloroprocaine was associated with significantly faster motor and sensory block regression (pMD = -57 min-140.3 min; P = 0.015 and

Study objective Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in postoperative pain management. While an increasing number of in vitro and animal studies point toward an inhibitory effect of NSAIDs on bone healing process, the few existing retro- and prospective clinical studies present conflicting data. Design The aim of this qualitative, systematic review was to investigate the impact of perioperative use of NSAIDs in humans on postoperative fracture/spinal fusion healing compared to other used analgesics measured as fracture nonunion with radiological control. Patients/interventions We performed a systematic literature search of the last 38 years using PubMed Embase and the Cochrane Controlled Trials Register including retro- and prospective clinical, human trials assessing the effect of NSAIDs on postoperative fracture/spinal fusion healing when used for perioperative pain management with a radiological follow up to assess eventual nonunion. Due to different study designs, drugs, dosages/exposition times and different methods to assess fracture nonunion, these studies were not pooled for a meta-analysis. A descriptive summary of all studies, level of evidence, study quality and study bias assessment using different scores were used. Main results Three prospective randomized controlled studies and thirteen retrospective cohort human studies were identified for a total of 12′895 patients. The overall study quality was low according to Jadad and Oxford Levels of Evidence scores. Conclusions Published results of human trials did not show strong evidence that NDAIDs for pain therapy after fracture osteosynthesis or spinal fusion lead to an increased nonunion rate. Reviewed studies present such conflicting data, that no clinical recommendation can be made regarding the appropriate use of NSAIDs in this context. Considering laboratory data of animal, human tissue research and recommendation of clinical reviews, a short perioperative exposition to NSAIDs is most likely not deleterious. However, randomized, controlled studies are warranted to support or refute this hypothesis.

BACKGROUND There is a wide variation of perineural catheter (PNC) colonization rates in the literature. The impact of skin disinfection on PNC colonization and inflammation is not clear. The objective of this prospective, randomized clinical study was to investigate the influence of alcoholic skin disinfection before PNC removal on the detection of bacteria on PNC. METHODS Two hundred patients receiving a PNC for orthopaedic surgery were random- ized to receive (with-group) or not (without-group) a skin disinfection with a sprayed alcoholic solution before removal of the PNC. Bacterial colonization and contamination of the PNC and clinical signs of inflammation and infection of the PNC insertion site were evaluated. Skin disinfection with a sprayed alcoholic solution and sterile removal of the distal and subcutaneous part of the PNC was performed after 72h or earlier if signs of infection occurred with semiquantitative culture and enrichment culture of both parts. RESULTS Alcoholic skin disinfection before PNC removal significantly reduced bacterial colonization with a reduction from 28% to 14% and from 32% to 17% for the tip and the subcutaneous part of the PNC, respectively (p < 0.05). Clinical signs of inflammation at the PNC insertion site were similar (73%) in the two groups. The detection of colonization in 54 (27%) out of 200 PNC did not correlate with clinical signs of inflammation independently of the number of bacteria isolated. Redness was noted in 71 % and 68 % of patients in the WITHOUT- and WITH-alcoholic skin disinfection-group respectively. Local pain on pressure was present in 28% and 19% in the without- and with-group respectively. CONCLUSIONS Alcoholic skin disinfection before PNC removal reduced the detection of PNC colonisation by 50%. There was no correlation between clinical signs of inflammation and PNC colonization.

Detection of circulating tumor cells (CTCs) relying on their expression of epithelial cell markers, such as epithelial cell adhesion molecule (EpCAM), has been commonly used. However, this approach unlikely captures CTCs that have undergone the process of epithelial-mesenchymal transition (EMT). In this study, we have induced EMT of in vitro prostate (PCa) and breast cancer (BCa) cell lines by treatment of transforming growth factor beta 1 (TGFβ(1)), a pleiotropic cytokine with transition-regulating activities. We found that the TGFβ(1)-treated, post-EMT cells exhibited up to a 45% reduction in binding affinity to antibodies against EpCAM (aEpCAM). To overcome this limitation, we designed our capture platform that integrates a unique combination of biomimetic cell rolling, dendrimer-mediated multivalent binding, and antibody cocktails of aEpCAM/aEGFR/aHER-2. Our capture surfaces resulted in up to 98% capture efficiency of post-EMT cells from mixtures of TGFβ(1)–treated and untreated cancer cells spiked in culture media and human blood. In a clinical pilot study, our CTC device was also able to capture rare CTCs from PCa patients with significantly enhanced capture sensitivity and purity compared to the control surface with aEpCAM only, demonstrating its potential to provide a reliable detection solution for CTCs regardless of their EMT status.

Background Evidence-based international expert consensus regarding anaesthetic practice in hip/knee arthroplasty surgery is needed for improved healthcare outcomes. Methods The International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) systematic review, including randomised controlled and observational studies comparing neuraxial to general anaesthesia regarding major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, genitourinary, thromboembolic, neurological, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, from 1946 to May 17, 2018 were queried. Meta-analysis and Grading of Recommendations Assessment, Development and Evaluation approach was utilised to assess evidence quality and to develop recommendations. Results The analysis of 94 studies revealed that neuraxial anaesthesia was associated with lower odds or no difference in virtually all reported complications, except for urinary retention. Excerpt of complications for neuraxial vs general anaesthesia in hip/knee arthroplasty, respectively: mortality odds ratio (OR): 0.67, 95% confidence interval (CI): 0.57–0.80/OR: 0.83, 95% CI: 0.60–1.15; pulmonary OR: 0.65, 95% CI: 0.52–0.80/OR: 0.69, 95% CI: 0.58–0.81; acute renal failure OR: 0.69, 95% CI: 0.59–0.81/OR: 0.73, 95% CI: 0.65–0.82; deep venous thrombosis OR: 0.52, 95% CI: 0.42–0.65/OR: 0.77, 95% CI: 0.64–0.93; infections OR: 0.73, 95% CI: 0.67–0.79/OR: 0.80, 95% CI: 0.76–0.85; and blood transfusion OR: 0.85, 95% CI: 0.82–0.89/OR: 0.84, 95% CI: 0.82–0.87. Conclusions Recommendation: primary neuraxial anaesthesia is preferred for knee arthroplasty, given several positive postoperative outcome benefits; evidence level: low, weak recommendation. Recommendation: neuraxial anaesthesia is recommended for hip arthroplasty given associated outcome benefits; evidence level: moderate-low, strong recommendation. Based on current evidence, the consensus group recommends neuraxial over general anaesthesia for hip/knee arthroplasty. Trial registry number PROSPERO CRD42018099935.

Background Chemokine receptor tyrosine sulfation plays a key role in the binding of chemokines. It has been suggested that receptor sulfation is heterogeneous, but no experimental evidence has been provided so far. The potent anti-HIV chemokine analog 5P12-RANTES has been proposed to owe its inhibitory activity to a capacity to bind a larger pool of cell surface CCR5 receptors than native chemokines such as CCL5, but the molecular details underlying this phenomenon have not been elucidated. Methods We investigated the CCR5 sulfation heterogeneity and the sensitivity of CCR5 ligands to receptor sulfation by performing ELISA assays on synthetic N-terminal sulfopeptides and by performing binding assays on CCR5-expressing cells under conditions that modulate CCR5 sulfation levels. Results Two commonly used anti-CCR5 monoclonal antibodies with epitopes in the sulfated N-terminal domain of CCR5 show contrasting binding profiles on CCR5 sulfopeptides, incomplete competition with each other for cell surface CCR5, and opposing sensitivities to cellular treatments that affect CCR5 sulfation levels. 5P12-RANTES is less sensitive than native CCL5 to conditions that affect cellular CCR5 sulfation. Conclusions CCR5 sulfation is heterogeneous and this affects the binding properties of both native chemokines and antibodies. Enhanced capacity to bind to CCR5 is a component of the inhibitory mechanism of 5P12-RANTES. General significance We provide the first experimental evidence for sulfation heterogeneity of chemokine receptors and its impact on ligand binding, a phenomenon that is important both for the understanding of chemokine cell biology and for the development of drugs that target chemokine receptors.

We have compared the efficacy of patient-controlled interscalene analgesia (PCIA) using ropivacaine with patient-controlled analgesia (PCA) using nicomorphine in 60 patients (n = 30 in each group), in a prospective, randomized study. In both groups, all patients received interscalene block with 0.75% ropivacaine before induction of anaesthesia. Six hours after interscalene block, patients in group PCIA received continuous infusion of 0.2% ropivacaine at a rate of 5 ml h-1 with a bolus dose of 3 or 4 ml and a lockout time of 20 min; patients in group PCA received continuous infusion of nicomorphine 0.5 mg h-1 and a bolus dose of 2 or 3 mg with a lockout time of 20 min. Control of pain was significantly better from 12 to 48 h after operation (except at 42 h) in group PCIA. Nausea and pruritus occurred significantly more frequently in group PCA. Patient satisfaction was greater in group PCIA. We conclude that the use of 0.2% ropivacaine using PCIA was an efficient way of managing pain after major shoulder surgery and compared favourably with PCA nicomorphine in terms of pain relief, side effects and patient satisfaction.

Background The influence of the muscular response elicited by neurostimulation on the success rate of interscalene block using a catheter (ISC) is unknown. In this investigation, we compared the success rate of ISC placement as indicated by biceps or deltoid, triceps, or both twitches. Methods Three hundred (ASA I-II) patients presenting for elective arthroscopic rotator cuff repair were prospectively randomized to assessment by biceps (Group B) or deltoid, triceps, or both twitches (Group DT). All ISCs were placed with the aid of neurostimulation. The tip of the stimulating needle was placed after disappearance of either biceps or deltoid, triceps, or both twitches at 0.3 mA. The catheter was advanced 2-3 cm past the tip of the needle and the block was performed using 40 ml ropivacaine 0.5%. Successful block was defined as sensory block of the supraclavicular nerve and sensory and motor block involving the axillary, radial, median, and musculocutaneous nerves within 30 min. Results Success rate was 98.6% in Group DT compared with 92.5% in Group B (95% confidence interval 0.01-0.11; P

This review discusses sedation for regional anaesthesia in the adult population. The first section deals with general aspects of sedation and shows that the majority of patients receiving sedation for regional anaesthesia are satisfied and would choose it again. Methods of assessing the level of sedation are discussed with emphasis on clinical measures. The pharmacology of the drugs involved in sedation is discussed, with propofol and remifentanil appearing to be the combination of choice for sedation in regional anaesthesia. The techniques for administering sedation are discussed and replacement of the traditional repeated boluses or continuous infusion with pharmacokinetic and patient-controlled systems is supported. Patient satisfaction studies suggest that patient-controlled systems are preferred.

BACKGROUND: Morphine and other opioids are routinely used systemically and as wound infusions in the postoperative period. Their effect on wound and fracture healing remains unclear. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of morphine on human fibroblasts. DESIGN: Laboratory in-vitro study. SETTING: Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human fibroblasts. INTERVENTION(S): Exposure of human fibroblast monolayers to several concentrations of morphine, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration, time and exposure-dependent cytotoxic effect of morphine-mediated apoptosis was observed. Simulated inflammatory conditions seemed to lessen toxic effects. CONCLUSION: Cytotoxic effects of morphine are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to morphine cytotoxicity especially in the presence of higher concentration and longer exposure times.

The ability of ultrasound to provide detailed anatomic visualization while avoiding radiation exposure continues to make it an appealing tool for many practitioners of chronic pain management. This review will present the most recent evidence regarding the use of ultrasound-guidance for the performance of interventional procedures in the treatment of chronic pain.For a variety of different procedures, studies continue to compare ultrasound-guided techniques to commonly used fluoroscopic or landmark-based techniques. Small, randomized controlled trials are beginning to demonstrate that ultrasound-guided approaches to interventional pain procedures can be as well tolerated and effective as the traditionally used techniques, while providing some potential advantages in terms of decreased radiation exposure, avoidance of vascular structures, and in some cases, improved efficiency and decreased rates of adverse effects.Despite continued interest in ultrasound-guided techniques for chronic pain management procedures, the evidence is still limited mainly to small, randomized trials and case series. For some procedures, such as stellate ganglion block and peripheral joint injections, recent evidence appears to be tilting in favor of ultrasound-guidance as the preferred technique, though fluoroscopy continues to be a much more reliable method for detection of intravascular uptake of injectate.

Fil: Taverna, CG. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina. Fil: Bosco-Borgeat, ME. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina. Fil: Mazza, M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina. Fil: Vivot, ME. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina. Fil: Davel, G. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina. Fil: Canteros, CE. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina. The aim of this work was to know the frequency and geographical distribution of genotypes and mating types of Cryptococcus neoformans and Cryptococcus gattii species complexes isolated from human infections in Argentina during the period from April 2009 to April 2011. A multicenter study was conducted, in which 372 isolates were obtained from 61 laboratories throughout the country. Of those, 98.8% of the isolates belonged to the C. neoformans species complex and 1.1% to the C. gattii species complex. Genotype VNI (MATα) was the most frequently isolated (n=326, 87.6%), followed by VNII (MATα) (n=22, 5.9%), the recently described VNII-VNIV (aADα) hybrid (n=14, 3.8%), VNIV (MATα) (n=4, 1.1%), VNIII (αADa) hybrid (n=1, 0.3%), and VNIII (αADα) hybrid (n=1, 0.3%). The Argentine Central region showed the greatest number of cases and genotype diversity. Interestingly, a relative high frequency was observed in genotype VNII (MATα) in the Cuyo, Northeast and Northwest regions and, also in VNII-VNIV (aADα) hybrids in the Northwest region. C. gattii species complex was isolated at a low rate; 3 VGI (MATα) and 1 VGII (MATα) isolates were obtained from the Northwest and Central regions. In conclusion, this study shows that genotype frequencies seem to vary among regions in Argentina and reveals a relatively high frequency of rare hybrids in the Northwest region. Further regional clinical and environmental studies may help to elucidate if those variations in frequencies are associated with the existence of regional ecological niches or any other regional factors. Genotipificación; Genotyping; Hybrids; Híbridos; Mating type; Tipo sexual

Background Matrix-metalloproteinases (MMP) and cancer cell invasion are crucial for solid tumour metastasis. Important signalling events triggered by inflammatory cytokines, such as tumour necrosis factor α (TNFα), include Src-kinase-dependent activation of Akt and focal adhesion kinase (FAK) and phosphorylation of caveolin-1. Based on previous studies where we demonstrated amide-type local anaesthetics block TNFα-induced Src activation in malignant cells, we hypothesized that local anaesthetics might also inhibit the activation and/or phosphorylation of Akt, FAK and caveolin-1, thus attenuating MMP release and invasion of malignant cells. Methods NCI-H838 lung adenocarcinoma cells were incubated with ropivacaine or lidocaine (1 nM-100 µM) in absence/presence of TNFα (20 ng ml−1) for 20 min or 4 h, respectively. Activation/phosphorylation of Akt, FAK and caveolin-1 were evaluated by Western blot, and MMP-9 secretion was determined by enzyme-linked immunosorbent assay. Tumour cell migration (electrical wound-healing assay) and invasion were also assessed. Results Ropivacaine (1 nM–100 μM) and lidocaine (1–100 µM) significantly reduced TNFα-induced activation/phosphorylation of Akt, FAK and caveolin-1 in NCI-H838 cells. MMP-9 secretion triggered by TNFα was significantly attenuated by both lidocaine and ropivacaine (half-maximal inhibitory concentration [IC50]=3.29×10−6 M for lidocaine; IC50=1.52×10−10 M for ropivacaine). The TNFα-induced increase in invasion was completely blocked by both lidocaine (10 µM) and ropivacaine (1 µM). Conclusions At clinically relevant concentrations both ropivacaine and lidocaine blocked tumour cell invasion and MMP-9 secretion by attenuating Src-dependent inflammatory signalling events. Although determined entirely in vitro, these findings provide significant insight into the potential mechanism by which local anaesthetics might diminish metastasis.

Background Epidural steroid injections are routinely performed under fluoroscopic guidance, but could also be performed using preprocedure ultrasound spine examination. Objectives To compare ultrasound-assisted and fluoroscopy-controlled epidural steroid injections with regard to technical feasibility (accuracy, average procedure time) and outcome (pain relief and degree of disability score). Design A randomised study. Setting University hospital between January 2010 and September 2012. Patients One hundred and twelve patients with axial chronic lower back and extremity pain diagnosed with degenerative diseases of the spine, receiving three lumbar interlaminar epidural steroid injections, were randomly assigned between two groups. Intervention In the fluoroscopic group, injections were performed under fluoroscopic guidance, and in the ultrasound group, ultrasound scanning of the lumbar spine was performed before the injection to determine the puncture site, depth of the epidural space and needle trajectory. Main outcome measures Procedure time, numbers of needle insertion attempts and needle passes, visual analogue scale for pain and Oswestry disability index at 1 and 3 months posttreatment. Results There was no significant difference between the two groups in mean procedure time, number of needle insertion attempts or needle passes. The mean pain intensity and degree of disability scores before the procedure, and at 1 and 3 months postprocedure, were similar in the two groups. Neither group had serious complications. Conclusion We have demonstrated the feasibility of ultrasound-assisted epidural steroid injections.

The incidence of neurologic damage after regional anesthesia is rare. However, this complication may have dramatic consequences for the patient because recovery may take several months. As nerve conduction studies and electromyography are the cornerstones of investigations in cases of postblock deficit, it is mandatory for the anesthesiologist performing regional anesthesia to have a basic understanding of these tests to discuss the cause with the surgeon and inform the patient about the prognosis.

A 33-YR-OLD woman, American Society of Anesthesiologists risk classification I, was referred for surgical treatment of left shoulder instability. Her medical history was unremarkable, but she had undergone two previous shoulder surgeries: anterior stabilization of left shoulder 3 yr ago followed by a posterior Bankart stabilization 2 yr later because of recurrent luxation and pain. At examination, she still complained about pain in her left shoulder, and movement was severely limited. A left Bankart operation and capsulotomy were scheduled. A preoperative interscalene catheter was placed according to the modified lateral approach. The interscalene brachial plexus was identified using a nerve stimulator (Stimuplex® HNS II, B. Braun Melsungen AG, Melsungen, Germany) connected to the proximal end of the metal inner part of a short beveled needle. A contraction of the deltoid muscle was observed with a current output of 0.35 mA, with an impulse duration of 0.1 ms. The insertion of the perineural catheter was performed using the cannula-over-needle technique with a plastic cannula (Polymedic®, Polyplex N-50 T, 20 gauge external diameter, te me na, Bondy, France). The catheter was introduced distally between the anterior and middle scalene muscle up to 3 cm. A bolus of 30 ml ropivacaine (0.5%) was administered, and the procedure was uneventful. No pain, dysesthesias, or paresthesias occurred at any time. Fifteen minutes later, a complete sensorimotor block of the left arm was observed. Then, general anesthesia with targetcontrolled infusion (TCI Diprifusor, SIMS Graseby Ltd., Watford, Herts, United Kingdom) of propofol and remifentanil was administered. The patient was positioned in the beach chair for surgery. The procedure lasted 3 h 30 min and was described by the surgeon as difficult. Postoperative analgesia was performed with patient-controlled interscalene analgesia using ropivacaine (0.2%) and was started 4 h after the end of the surgery. The pump settings were basal rate of 5 ml/h with supplementary boli of 4 ml for every 20 min. The patient was pain free, and the patient-controlled interscalene analgesia was stopped after 54 h. Even after 36 h of termination of patient-controlled interscalene analgesia, no motor or sensory recovery was observed. An ultrasonography of the brachial plexus was performed to exclude a hematoma and revealed no irregular finding. A complete neurologic examination including neurophysiologic recordings on the following day (72 h after surgery) demonstrated a motor and sensory incomplete lesion of nerve fibers originating from the upper brachial plexus (involving the following muscles: deltoid M0/5, biceps M0/5, and triceps M3/5). Motor nerve conduction studies (figs. 1 and 2) and somatosensory-evoked potentials (SSEPs) of the median and ulnar nerves that originate from the lower brachial plexus revealed normal recordings. Electromyography at the initial examination did not show signs of denervation (fibrillation or positive waves) but resulted in complete paralysis (no retrievable voluntary electromyography activity). The later finding at this early stage after injury can be in line with a neurapraxia (conduction failure) or axonotmesis (structural neural damage). Eventually, 1 month later, at the first follow-up, electromyographies showed signs of denervation most severe within the deltoid and biceps muscles, disclosing objective signs of neural damage (fig. 3) congruent to the clinical condition in which no motor improvement was observed. Six months later, although no clinical improvement occurred, a surgical exploration was performed that revealed no pathologic findings. At this time, a perioperative stimulation of the trunks of the brachial plexus elicited reliable responses for the three trunks. In repeated electromyographic recordings during a period of 2 yr, increasing signs of motor recovery could be observed, although the patient still demonstrated severe proximal muscle weakness that could not be * Professor and Chief-of-Staff, † Consultant, Department of Anesthesiology, ‡ Professor and Chairman, Spinal Cord Injury Center, University of Zurich, Balgrist University Hospital, Zurich, Switzerland.

We have investigated the interaction between magnesium sulphate 40 mg kg-1 i.v. and vecuronium. First, we determined the effect of pretreatment with magnesium on the potency of vecuronium using a single bolus dose-response technique. In addition, we compared the time course of vecuronium-induced neuromuscular block (vecuronium 100 micrograms kg-1) with and without magnesium pretreatment. For both parts, neuromuscular block was assessed by electromyography. In addition, the effect of magnesium pretreatment on vecuronium-induced neuromuscular block was investigated in the context of rapid sequence induction of anaesthesia. We found that the neuromuscular potency of vecuronium was increased by pretreatment with magnesium sulphate. The ED50 and ED90 of vecuronium with MgSO4 were 25% lower than without MgSO4 (ED50: 21.3 vs 26.9 micrograms kg-1; ED90: 34.2 vs 45.7 micrograms kg-1; P0.05 for both). Mean onset time was 147.3 (SD 22.2) s in the MgSO4-vecuronium group vs 297.3 (122) s for controls (P0.05). Clinical duration was prolonged (MgSO4-vecuronium 43.3 (9) min vs 25.2 (5.1) min for controls; P0.05). This was also true for the recovery index (20.1 (6.6) min vs 10.6 (3.4) min; P0.05) and duration to 75% recovery (63.4 (9.9) min vs 35.8 (6.9) min; P0.05). In the context of rapid sequence induction, pretreatment with MgSO4 improved the intubating score of vecuronium compared with vecuronium without MgSO4, reaching the same quality as that with suxamethonium 1 mg kg-1. We conclude that magnesium pretreatment increased the neuromuscular potency of vecuronium, in addition to modifying the time course of its neuromuscular block.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a potentially severe food allergy. Physical exercise, NSAID, alcohol, infectious diseases and estrogens are recognized cofactors, able to reduce the amount of allergen needed to achieve a threshold for the induction of anaphylaxis. Various kinds of causative food but only a few responsible proteins have been identified. The best known is wheat ω5-gliadine. An oral food challenge remains the gold standard to prove the diagnosis. Its clinical application remains difficult and includes an allergen challenge, a cofactor challenge and a third step which integrates both of them in a single test. Gluten flour and NSAID + alcohol combination seem more efficient than respectively wheat flour and physical exercise in a provocation test condition.L’anaphylaxie alimentaire à l’effort est une allergie alimentaire potentiellement sévère. L’exercice physique, les AINS, l’alcool, les infections et les œstrogènes sont des cofacteurs reconnus, capables de diminuer la quantité d’allergènes nécessaire à l’atteinte d’un seuil anaphylactique. Si le panel d’aliments incriminés est large, seules quelques protéines responsables ont été à ce jour identifiées. La plus connue est l’ω5-gliadine du blé. En cas d’incertitude diagnostique, un test de provocation est indiqué. Son application clinique reste difficile et inclut de tester l’allergène de manière isolée et le cofacteur puis d’intégrer les deux dans un même test. La farine de gluten et la combinaison AINS + alcool ont une sensibilité supérieure respectivement à la farine de blé et à l’exercice physique en situation de provocation.

Introduction Continuous regional analgesia is an established technique for effective postoperative pain treatment, particularly after orthopedic surgical procedures. Even if it has been increasingly applied to the outpatient setting as well, many anesthesiologists are still reluctant to discharge patients with a perineural catheter in place. Aim of this review was to clarify the evidences about safety and effectiveness of outpatient continuous peripheral nerve blocks. Evidence acquisition A systematic review of all prospective, randomized, double-blinded, placebo-controlled trials of the last 20 years on outpatient continuous peripheral nerve blocks after ambulatory orthopedic surgery was performed, using both PubMed and OVID databases were. Study quality was assessed using the modified Jadad Scale. Primary outcomes were pain at 24 and 48 hours and morphine consumption. Evidence synthesis Five studies matched the inclusion criteria and were considered of good quality to be included in the review process. All these studies consistently showed a better pain control both at rest and during movement within the first postoperative day, leading to a reduced opioid consumption in patients treated with outpatient continuous regional analgesia. However, only three studies showed these advantages to be sustained longer than the first 24 hours postoperatively. No severe complications were reported. Conclusions High-quality evidences about outpatient regional analgesia are scarce. Considering the advantages of continuous peripheral nerve blocks in the inpatient setting more prospective studies assessing also functional recovery are needed to further implement these techniques in the ambulatory setting.

Background Significant hypotension is frequent after spinal anaesthesia and fluid administration as therapy is usually empirical. Inferior vena cava (IVC) ultrasound (US) is effective to assess fluid responsiveness in critical care patients. The aim of this study was to evaluate the IVCUS-guided volume optimization to prevent post-spinal hypotension. Methods In this prospective, randomized, cohort study, 160 patients scheduled for surgery under spinal anaesthesia were randomized into a study group (IVCUS-group), consisting of an IVCUS analysis before spinal anaesthesia with IVCUS-guided volume management and a control group (group C) with no IVCUS assessment. The primary outcome was a relative risk reduction in the incidence of hypotension between the groups; secondary outcomes were the need for vasoactive drugs and the amounts of fluids required after spinal anaesthesia. We also tested the hypothesis of a correlation between IVC collapsibility index and hypotension after spinal anaesthesia. Results The relative risk reduction of hypotension between the groups was 35% (IVCUS-group 27.5%, Group C 42.5%, P =0.044, CI=95%). The need for vasoactive drugs in the IVCUS-group was significantly lower compared to the C-group ( P =0.015), while the total amount of fluids was significantly superior higher in the IVCUS group ( P r 2 =0.32), but could not be used to predict postspinal anaesthesia hypotension. Conclusions IVCUS is an effective method to prevent postspinal anaesthesia hypotension by IVCUS-guided fluid administration before spinal anaesthesia. Clinical trial registration www.clinicaltrials.gov - NCT02271477.

PURPOSE OF REVIEW: Sedation is a well recognized technique to improve patients' acceptance and comfort during regional anesthesia. The use of this technique is growing exponentially and is nowadays applied not only in the operating room but also in many other different locations within and outside the hospital. RECENT FINDINGS: Different methods of applying sedation are used. Recent studies have shown that the target-controlled infusion technique is advantageous in this context, as the incidence of side effects is lower and the amount of infused drugs is decreased. Several devices have been investigated in this setting, but, to date, none of them has been shown to be reliable. The combination of propofol and remifentanil for the purpose of analgosedation is increasingly used. The benefits of these drugs given simultaneously are supported by several investigations. Dexmedetomidine, the most recently introduced sedative, still needs to be more extensively studied in this context. Nurse-driven sedation will be inevitable in the future. Anesthesiologists should build up guidelines and nurse-teaching programs to fulfill this new development. SUMMARY: The explosion of sedation well beyond the world of regional anesthesia has raised new challenges. Some sedative procedures will be performed more and more often by nonanesthesiologists in the future. This trend is inevitable due to limited resources and stresses on the importance of building up education and teaching programs for nonanesthesiologists. The need for reliable devices for monitoring of sedation and new hypnotics, which have even better phamacokinetics than those available, are needed to match the new issues of sedation.

Some components of generalized anxiety disorder, such as physical symptoms, are thought to reflect autonomic nervous system arousal. This study primarily assessed the relationships between psychophysiological and clinical measures using venlafaxine extended release or applied relaxation, and secondarily, the impact of combination treatment in patients not remitting after 8 weeks. Fifty-eight patients were randomly assigned to 8 weeks of treatment with either venlafaxine or applied relaxation (Phase I). Non-remitted patients received combination treatment for an additional 8 weeks (Phase II). Assessments included the Hamilton Anxiety Scale (HAM-A), Beck Depression Inventory, Penn State Worry Questionnaire and the Stroop Color-Word Task coupled with electrophysiological measures (skin conductance and frontalis electromyography (EMG)). In Phase 1, a time effect was found for the clinical and skin conductance measures. Thirteen patients from each group were in remission. In Phase 2, seven additional patients remitted. Baseline psychophysiological measures were not associated with baseline clinical variables or with clinical outcomes. Independently of treatment allocation, a reduction in frontal EMG values at week 4 was significantly associated with a decrease in HAM-A scores at week 8. At week 4, responders from the applied relaxation group had lower electrophysiological activity than the venlafaxine group. Baseline psychophysiological measures were not linked with clinical measures at study inclusion or with treatment response. Frontal EMG response at week 4 is a possible predictor of treatment response. Treatment combination enhances treatment response after initial failure.

Platelets play crucial functions in hemostasis and the prevention of bleeding. During H1N1 influenza A virus infection, platelets display activation markers. The platelet activation triggers during H1N1 infection remain elusive. We observed that H1N1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. These activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). Considering that immune complexes in the H1N1 pandemic were reported to play a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulin G (IgG) to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of low-affinity type 2 receptor for Fc portion of IgG (FcγRIIA), a receptor for immune complexes, independently of thrombin. Using a combination of in vitro and in vivo approaches, we found that the antibodies from H3N2-immunized mice activate transgenic mouse platelets that express FcγRIIA when put in the presence of H1N1, suggesting that cross-reacting influenza antibodies suffice. Alternatively, H1N1 can activate platelets via thrombin formation, independently of complement and FcγRIIA. These observations identify both the adaptive immune response and the innate response against pathogens as 2 intertwined processes that activate platelets during influenza infections.

Toll-like receptors (TLR) recognize pathogen-associated molecular patterns and play important roles in the innate immune system. While single-stranded viral RNA is the natural ligand of TLR7/TLR8, the imidazoquinoline resiquimod (R-848) is recognized as a potent synthetic agonist of TLR7/TLR8. We investigated the effects of TLR7/8 activation on lipid mediator production in polymorphonuclear leukocytes exposed to R-848. Although R-848 had minimal effects by itself, it strongly enhanced leukotriene B4 formation on subsequent stimulation by fMLP, platelet-activating factor, and the ionophore A23187. R-848 acted via TLR8 but not TLR7 as shown by the lack of effect of the TLR7-specific ligand imiquimod. Priming with R-848 also resulted in enhanced arachidonic acid release and platelet-activating factor formation following fMLP stimulation, as well as enhanced prostaglandin E2 synthesis following the addition of arachidonic acid. Western blot analysis demonstrated that R-848 induced the phosphorylation of the cytosolic phospholipase A2alpha, promoted 5-lipoxygenase translocation and potently stimulated the expression of the type 2 cyclooxygenase. Bafilomycin A1, an inhibitor of endosomal acidification, efficiently inhibited all R-848-induced effects. These studies demonstrate that TLR8 signaling strongly promotes inflammatory lipid mediator biosynthesis and provide novel insights on innate immune response to viral infections.

Background and objectives: Same-day surgery is common for foot surgery. Continuous regional anesthesia for outpatients has been shown effective but the economic impact on the perioperative process-related healthcare costs remains unclear. Methods: One hundred twenty consecutive patients were included in this assessor-blinded, prospective cohort study and allocated according to inclusion criteria in the day-care or in the in-patient group. Standardized continuous popliteal sciatic nerve block was performed in both groups for 48 h using an elastomeric pump delivering ropivacaine 0.2 % at a rate of 5 ml/h with an additional 5 ml bolus every 60 min. Outpatients were discharged the day of surgery and followed with standardized telephone interviews. The total direct health costs of both groups were compared. Moreover, the difference in treatment costs and the difference in terms of quality of care and effectiveness between the groups were compared. Results: Total management costs were significantly reduced in the day-care group. There was no difference between the groups regarding pain at rest and with motion, persistent pain after catheter removal and the incidence of PONV. Persistent motor block and catheter inflammation/infection were comparable in both groups. There was neither a difference in the number of unscheduled ambulatory visits nor in the number of readmissions. Conclusions: Day-care continuous regional analgesia leads to an overall positive impact on costs by decreasing the incidence of unplanned ambulatory visits and unscheduled readmissions, without compromising on the quality of analgesia, patients’ satisfaction, and safety.

Background To potentially optimize intubation skill teaching in an American Heart Association® Airway Management Course® for novices, we investigated the transfer of skills from video laryngoscopy to direct laryngoscopy and vice versa using King Vision® and Macintosh blade laryngoscopes respectively. Methods Ninety volunteers (medical students, residents and staff physicians) without prior intubation experience were randomized into three groups to receive intubation training with either King Vision® or Macintosh blade or both. Afterwards they attempted intubation on two human cadavers with both tools. The primary outcome was skill transfer from video laryngoscopy to direct laryngoscopy assessed by first attempt success rates within 60 s. Secondary outcomes were skill transfer in the opposite direction, the efficacy of teaching both tools, and the success rates and esophageal intubation rates of Macintosh blade versus King Vision®. Results Performance with the Macintosh blade was identical following training with either Macintosh blade or King Vision® (unadjusted odds ratio [OR] 1.09, 95% confidence interval [95% CI] 0.5–2.6). Performance with the King Vision® was significantly better in the group that was trained on it (OR 2.7, 95% CI 1.2–5.9). Success rate within 60 s with Macintosh blade was 48% compared to 52% with King Vision® (OR 0.85, 95% CI 0.4–2.0). Rate of esophageal intubations with Macintosh blade was significantly higher (17% versus 4%, OR 5.0, 95% CI 1.1–23). Conclusions We found better skill transfer from King Vision® to Macintosh blade than vice versa and fewer esophageal intubations with video laryngoscopy. For global skill improvement in an airway management course for novices, teaching only video laryngoscopy may be sufficient. However, success rates were low for both devices. Electronic supplementary material The online version of this article (doi:10.1186/s12871-016-0296-9) contains supplementary material, which is available to authorized users.

Short-acting regional anesthetics have already been successfully used for peripheral nerve blocks in an ambulatory surgery setting. However, the impact on direct and indirect perioperative costs comparing 2 different short-acting local anesthetics has not been performed yet.Observational, prospective, case-control, cost-minimization study.Operating room, regional hospitalOne hundred adult American Society of Anesthesiologists status I-III patients scheduled for popliteal block after minor ambulatory foot surgery.Application of 30 mL chloroprocaine 3% or of 30 mL mepivacaine 1.5% for anesthesia.Cost-minimization evaluation. Direct and indirect perioperative costs were calculated. Block success, onset time and block duration, patient satisfaction, and unplanned outpatient visits or readmissions after discharge were also assessed.Onset time (sensory: 4.3 ± 2.4 vs 11.5 ± 3.2 minutes; motor: 7.1 ± 3.7 vs 18.4 ± 4.5 minutes) and block duration (sensory: 105 ± 26 vs 317 ± 46 minutes; motor: 91 ± 25 vs 216 ± 31 minutes) were significantly shorter (P.001) when chloroprocaine 3% was used. This translated to P.001, basically due to a faster discharge home 55 ± 1 vs 175 ± 2 minutes; P.001) in favor of chloroprocaine 3%, without negatively affecting either block efficacy or patients satisfaction. There were no unplanned outpatient visits or readmissions and no complications in the follow-up at 6 weeks.We conclude that the more expensive chloroprocaine 3% for ambulatory foot surgery can reduce total perioperative costs and reduce length of stay in outpatient patients. Moreover, the saved time and personal resources could be used for additional cases, further increasing the revenues of an ambulatory surgical center.

Study objective Beach chair position is considered a potential risk factor for central neurological events particularly if combined with low blood pressure. The aim of this study was to assess the impact of regional anesthesia on cerebral blood flow and neurobehavioral outcome. Design This is a prospective, assessor-blinded observational study evaluating patients in the beach chair position undergoing shoulder surgery under regional anesthesia. Setting University hospital operating room. Patients Forty patients with American Society of Anesthesiologists classes I-II physical status scheduled for elective shoulder surgery. Interventions Cerebral saturation and blood flow of the middle cerebral artery were measured prior to anesthesia and continued after beach chair positioning until discharge to the postanesthesia care unit. The anesthesiologist was blinded for these values. Controlled hypotension with systolic blood pressure≤100mm Hg was maintained during surgery. Measurements Neurobehavioral tests and values of regional cerebral saturation, bispectral index, the mean maximal blood flow of the middle cerebral artery, and invasive blood pressure were measured prior to regional anesthesia, and measurements were repeated after placement of the patient on the beach chair position and every 20 minutes thereafter until discharge to postanesthesia care unit. The neurobehavioral tests were repeated the day after surgery. Main results The incidence of cerebral desaturation events was 5%. All patients had a significant blood pressure drop 5 minutes after beach chair positioning, measured at the heart as well as the acoustic meatus levels, when compared with baseline values ( P P =.136) or the maximal blood flow of the middle cerebral artery ( P =.212) at the same time points. Some neurocognitive tests showed an impairment 24 hours after surgery ( P Conclusions Beach chair position in patients undergoing regional anesthesia for shoulder surgery had no major impact on cerebral blood flow and cerebral oxygenation. However, some impact on neurobehavioral outcome 24 hours after surgery was observed.

The presence of the cryptic species belonging to the Candida glabrata complex has not been studied in Argentina. We analyzed a collection of 117 clinical isolates of C. glabrata complex belonging to a National Culture Collection of Instituto Nacional de Microbiología “Dr. Carlos G. Malbrán” from Argentina (40 isolates from blood samples, 18 from other normally sterile sites, 20 from vagina, 14 from urine, 7 from oral cavity, 3 from catheter, 1 from a stool sample and 14 isolates whose clinical origin was not recorded). The aims of this work were to determine the prevalence of the cryptic species Candida nivariensis and Candida bracarensis and to evaluate the susceptibility profile of isolates against nine antifungal drugs. Identification was carried out by using classical phenotypic tests, CHROMagar™ Candida, PCR and MALDI-TOF. The minimal inhibitory concentrations of amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, voriconazole, ketoconazole, posaconazole, caspofungin and anidulafungin were determined according to the EDef 7.3 (EUCAST) reference document. Of the 117 isolates, 114 were identified as C. glabrata and three as C. nivariensis by using PCR and MALDI-TOF. There were no major differences between C. nivariensis and C. glabrata susceptibility profiles. No resistant strains were found to echinocandins. We have found that the percentage of C. nivariensis in our culture collection was 2.56. This is the first description of C. nivariensis in Argentina, and data obtained could contribute to the knowledge of the epidemiology of this cryptic species. Fil: Morales López, Soraya Eugenia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Taverna, Costanza G.. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Bosco Borgeat, María Eugenia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Maldonado, Nuria Ivana. Laboratorios Domeq y Lafage; Argentina Fil: Vivot, Walter. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Szusz, Wanda. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina Fil: Garcia, Guillermo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina Fil: Córdoba, Susana Beatríz. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina

Background Invasion of extracellular matrix is a hallmark of malignant tumors. Clamping maneuvers during cancer surgery reduce blood loss, but trigger reperfusion injury (RI). RI increases cancer recurrence in the reperfused organ through up-regulation of matrix metalloproteinase-9 (MMP-9). Interleukin-8 is an important cytokine in RI promoting accumulation of neutrophils, a major source of MMP-9. Volatile anesthetics were demonstrated to reduce RI. We hypothesized that these anesthetics might attenuate MMP-9 up-regulation and consequently tumor cell invasion in RI. Methods Isolated human neutrophils (n = 6) were preconditioned with sevoflurane or desflurane, followed by stimulation with interleukin-8, phorbol myristate acetate, or chemokine CXC-ligand 1 (CXCL1) to differentiate intracellular pathways. MMP-9 release and activity were quantified by enzyme-linked immunosorbent assay and zymography, respectively. CXC-receptor-2 (CXCR2) expression and phosphorylation of extracellular signal-regulated kinases 1/2 were assessed by flow cytometry. The impact of MMP-9 on the invasion of neutrophils and MC-38 colon cancer cells was assessed using Matrigel-coated filters (n = 6). Results Preconditioning reduced interleukin-8-induced MMP-9-release by 41% (±13, 5%, sevoflurane) and 40% (±13%, desflurane). This was also evident following stimulation of CXCR2 with CXCL1. No impact on phosphorylation of extracellular signal-regulated kinases 1/2 and MMP-9 release was observed with receptor-independent stimulation of protein kinase C with phorbol myristate acetate. Preconditioning reduced transmigration of neutrophils and MC-38 tumor cells to baseline levels. Discussion Volatile anesthetics impair neutrophil MMP-9 release and interfere with pathways downstream of CXCR2, but upstream of protein kinase C. Through down-regulation of MMP-9, volatile anesthetics decrease Matrigel breakdown and reduce subsequent migration of cancer cells in vitro.

Candida pseudorugosa is a novel species closely related to Candida rugosa for which only one case has been reported. We report the first case of a bloodstream infection in humans caused by a Candida sp. closely related to C. pseudorugosa . We contribute evidence to show this organism as a potential human pathogen that may be misidentified by conventional methods, also pointing out its lower sensitivity to azoles and other antifungal agents.

Objective There is increasing evidence of a role for Toll-like receptors (TLRs) in inflammatory arthritis. The extra domain A (ED-A)–containing isoform of fibronectin is generated under pathologic conditions such as rheumatoid arthritis, and ED-A has been identified as an endogenous TLR-4 ligand. Leukotriene B4 (LTB4) and polymorphonuclear neutrophils (PMNs) play a critical role in murine models of inflammatory arthritis. The aim of this study was therefore to investigate the putative effects of ED-A on leukotriene biosynthesis and PMN migration through TLR signaling. Methods The effect of recombinant human ED-A (rhED-A) on leukotriene biosynthesis was evaluated in isolated human blood PMNs and monocytes by high-performance liquid chromatography. The capacity of rhED-A to stimulate PMN migration was evaluated using a transendothelial/matrix migration assay in vitro and the mouse air-pouch model in vivo. Results Recombinant human ED-A efficiently primed the biosynthesis of LTB4 in PMN and monocyte suspensions. This priming effect was dependent on TLR-4 activation, since the TLR-4–signaling inhibitor CLI-095 completely blocked the effect of rhED-A but not that of other TLR ligands (R-848, Pam2CSK4) or cytokines. Moreover, rhED-A stimulated transendothelial migration of PMNs in vitro, which was inhibited by 50–60% with the LTB4 receptor 1 (BLT1) antagonist CP105,696 or the cytosolic phospholipase A2α inhibitor pyrrophenone. In vivo, rhED-A induced a significant PMN recruitment into the air pouch of C3H/HeOuJ mice (expressing functional TLR-4), but not in C3H/HeJ mice (expressing nonsignaling TLR-4). Conclusion These results demonstrate the ability of rhED-A to promote LTB4 biosynthesis and PMN migration through TLR-4 activation, thus providing new insights on TLR-dependent mechanisms of regulation of LTB4 biosynthesis and PMN infiltration in inflammatory joint diseases.