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Background: Ankle blocks typically include the block of 5 nerves, the 4 branches that trace their origin back to the sciatic nerve plus the saphenous nerve (SaN). The sensory area of the SaN in the foot is variable. Based on our clinical experience, we decided to study the sensory distribution of the SaN in the foot and determine whether the block of this nerve is necessary as a component of an ultrasound-guided ankle block for bunion surgery.Methods: One hundred patients scheduled for bunion surgery under ankle block were prospectively studied. We performed ultrasound-guided individual blocks of the tibial, deep peroneal, superficial peroneal, and sural nerves. After obtaining complete sensory block of these nerves, we mapped the SaN sensory territory as such area without anesthesia on the medial side of the foot.Results: Every nerve block was successful within 10 minutes of injection. The saphenous territory extended into the foot to 57 ± 13 mm distal to the medial malleolus. This distal margin was 22 ± 11 mm proximal to the first tarsometatarsal joint. The proximal end of the surgical incision was located 1 cm distal to the first tarsometatarsal joint. In only 3 patients (3%), the area of SaN innervation reached the proximal end of the planned incision.Conclusions: Ultrasound-guided ankle block is a highly effective technique for bunion surgery. The sensory territory of the SaN in the foot seems to extend only to the midfoot. According to our sample, 97% of the patients undergoing bunion surgery under an ankle block would not benefit from having a SaN block. [ABSTRACT FROM AUTHOR]

Background and Objectives: Major nerves and vessels run alongside each other in a "neurovascular bundle" kept together by connective tissue that is often referred to by anatomists, surgeons, and anesthesiologists as the "sheath." Our goal was to macroscopically demonstrate the brachial plexus sheath in embalmed and fresh cadaver dissections.Methods: Systematic dissections were performed on 11 embalmed cadavers (6 females and 5 males), plus one fresh, unembalmed male cadaver. Dissections were started in the arm, and progressed proximally to the axilla and the supraclavicular area. Notes and photographic documentation were obtained.Results: A sheath around the neurovascular bundle of the brachial plexus was visible to the naked eye in every dissection. The sheath had a fibrous external appearance, and was filled with loose connective tissue. No evidence of septa was found.Conclusions: We observed a macroscopic fibrous structure surrounding the plexus, which was filled with loose connective tissue lacking any apparent organization. [ABSTRACT FROM AUTHOR]

DNA can be readily amplified through replication, enabling the detection of a single-target copy. A comparable performance for proteins in immunoassays has yet to be fully assessed. Surface-plasmon-resonance (SPR) serves as a probe capable of performing assays at concentrations typically around 10⁻⁹ molar. In this study, plasmonic single-molecule assays for both proteins and DNA are demonstrated, achieving limits-of-detections (LODs) as low as 10⁻ 2 ⁰ molar (1 ± 1 molecule in 0.1 mL), even in human serum, in 1 h. This represents an improvement in typical SPR LODs by eleven orders-of-magnitude. The single-molecule SPR assay is achieved with a millimeter-wide surface functionalized with a physisorbed biolayer comprising trillions of recognition-elements (antibodies or protein-probe complexes) which undergo an acidic or alkaline pH-conditioning. Potentiometric and surface-probing imaging experiments reveal the phenomenon underlying this extraordinary performance enhancement. The data suggest an unexplored amplification process within the biomaterial, where pH-conditioning, driving the biolayer in a metastable state, induces a self-propagating aggregation of partially misfolded proteins, following single-affinity binding. This process triggers an electrostatic rearrangement, resulting in the displacement of a charge equivalent to 1.5e per 10 2 recognition elements. Such findings open new opportunities for reliable SPR-based biosensing at the physical detection limits, with promising applications in point-of-care plasmonic systems., (© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

A ground-breaking graphene-based biosensor designed for label-free detection of immunoglobulin M (IgM) achieving a remarkable concentration of 100 zeptomolar (10 -19 m), is reported. The sensor is a two-terminal device and incorporates a millimeter-wide gold interface, bio-functionalized with ≈10 12 anti-IgM antibodies and capacitively coupled to a bare graphene electrode through a water-soaked paper strip. In this configuration, few affinity binding events trigger a collective electrostatic reorganization of the protein layer, leading to an extended surface potential (SP) shift of the biofunctionalized Au surface. The SP shift, mediated by electrolyte capacitive coupling, induces a corresponding shift in the Fermi level of graphene. This shifts the graphene phonon frequencies, which are measured by Raman spectroscopy. Decoupling the sensing interface from the transducing graphene layer provides flexibility in surface chemistry modifications, while preserving the graphene integrity. A key aspect of this biosensor is its ability to precisely determine the graphene charge neutrality point from the voltage dependence of phonon frequency shifts, enabling detections of biomarker at unprecedented low concentrations. The integration of graphene with optical probing demonstrates a proof-of-concept and establishes a ground-breaking approach to in situ biomarker detection, setting the stage for a future generation of portable opto-electronic high-performance diagnostic tools for single-marker detection., (© 2025 The Author(s). Small Methods published by Wiley‐VCH GmbH.)

Background: Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks., Methods: We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%-74% agreement., Results: A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research., Conclusions: We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care., Competing Interests: Competing interests: EA: grants from Swiss Academy for Anesthesia Research, Bbraun, Swiss National Science Foundation. Honoraria from Bbraun and Sintetica. JG: consulting fees from Pacira Biosciences and Pajunk Medical. AP: honoraria from FuijiFilm Sonosite. MW: advisory Board for Sintetica, Honoraria from Wisonic and Medovate. SA: Advisory Panel for DATAR innovations. JA: moderator of the Working Group Regional Anaesthesia Switzerland, Honoraria from Medtronic and Sintetica. AMRA: honoraria form AllerganSébastien Bloc—Consulting fees from BBraun—GE Medical Systems—Pajunk—Pfizer SAS. JB: Consulting fees from Intelligent Ultrasound. BC: jonoraria from Bbraun and Rivanna, Consulting from Stryker and Flat Medical, Research funding from Pacira, Share Options from Flat Medical. AC: speaking honoraria from GE Healthcare, royalties from textbook Oxford University Press. SC: consulting fees from MSD, Bbraun Medical, Wisonic, research grants from BARA (Belgian association of Regional anesthesia), ESRA and BeSARP (Belgian anesthesia society) HE-Consulting/Advisory Board Neuronoff, SPR, GateScience, NeuronoffBenjamin Fox—Speaking fees from Medovate and Sintetica. SG: consulting and speaking fees from MSD Switzerland. PH: royalties from Bestek Products. NH: Honoraria from Butterfly Network. RMGH- Honoraria from GE Healthcare. MH: consulting fees from Pacira Biosciences, Honoraria from Parcira Biosciences and Pajunk Medical. BMI: research funding to institution from SPR Therapeutics, Infutronix, Epimed International. AM: Consultant fees from Intelligent Ultrasound. CM: consultant fees from Masimo Corporation. SGM: Owner SGM Consulting, Partner Parvizi Surgical Innovations, Patent for Multicatheter infusion system. AN: Research support from SPR Therapeutics. SLO: Royalties from book Wolters-Kluwer. APawa: Honoraria from GE Healthcare, Consulting fees from Pacira Biosciences. PP: equipment support from Sonosiite Fujifilm Canada. MPS: Medovate speaking but no honoraria paid. SKS- Cofounder of Gate Science (developing a catheter for performing nerve blocks) JS: consulting fees from Sintetica. RT: Consulting fees from Clarius Mobile Health. VU: Associate Editor of the Canadian Journal of Anesthesia and Regional Anesthesia & Pain Medicine journals. TV: honoraria from CSL Behring, Pajunk., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The development of ultrasensitive electronic sensors for in vitro diagnostics is essential for the reliable monitoring of asymptomatic individuals before illness proliferation or progression. These platforms are increasingly valued for their potential to enable timely diagnosis and swift prognosis of infectious or progressive diseases. Typically, the responses from these analytical tools are recorded as digital signals, with electronic data offering simpler processing compared to spectral and optical data. However, preprocessing electronic data from potentiometric biosensor arrays is still in its infancy compared to more established optical technologies. This study utilized the Single-Molecule with a Large Transistor (SiMoT) array, which has achieved a Technology Readiness Level of 5, to explore the impact of data preprocessing on electronic biosensor outcomes. A dataset consisting of plasma and cyst fluid samples from 37 patients with pancreatic precursor cyst lesions was analyzed. The findings revealed that standard signal preprocessing can produce misleading conclusions due to artifacts introduced by mathematical transformations. The study offers strategies to mitigate these effects, ensuring that data interpretation remains accurate and reflective of the underlying biochemical information in the samples., (© 2024 The Author(s). ChemPlusChem published by Wiley-VCH GmbH.)

Pancreatic cancer, ranking as the third factor in cancer-related deaths, necessitates enhanced diagnostic measures through early detection. In response, SiMoT-Single-molecule with a large Transistor multiplexing array, achieving a Technology Readiness Level of 5, is proposed for a timely identification of pancreatic cancer precursor cysts and is benchmarked against the commercially available chemiluminescent immunoassay SIMOA (Single molecule array) SP-X System. A cohort of 39 samples, comprising 33 cyst fluids and 6 blood plasma specimens, undergoes detailed examination with both technologies. The SiMoT array targets oncoproteins MUC1 and CD55, and oncogene KRAS, while the SIMOA SP-X planar technology exclusively focuses on MUC1 and CD55. Employing Principal Component Analysis (PCA) for multivariate data processing, the SiMoT array demonstrates effective discrimination of malignant/pre-invasive high-grade or potentially malignant low-grade pancreatic cysts from benign non-mucinous cysts. Conversely, PCA analysis applied to SIMOA assay reveals less effective differentiation ability among the three cyst classes. Notably, SiMoT unique capability of concurrently analyzing protein and genetic markers with the threshold of one single molecule in 0.1 mL positions it as a comprehensive and reliable diagnostic tool. The electronic response generated by the SiMoT array facilitates direct digital data communication, suggesting potential applications in the development of field-deployable liquid biopsy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Infective endocarditis caused by Gemella species is increasingly recognized as an emerging clinical entity. Gemella species are fastidious gram-positive cocci that are typically commensal organisms but can become opportunistic pathogens. This systematic review aimed to provide a comprehensive overview of endocarditis due to  Gemella  species by synthesizing existing evidence. A total of 52 case reports were identified through a rigorous search and selection process. The most prevalent causative species were G. morbillorum (46.3%) and G. haemolysans (25.9%), with a striking male predominance (79.6%). The clinical presentation was largely nonspecific, mirroring typical infective endocarditis. However, the indolent nature of the illness and fastidious growth requirements of Gemella species often led to diagnostic delays. Echocardiography, particularly transesophageal echocardiography, played a crucial role in the diagnosis, enabling the detection of valvular vegetation and the assessment of complications. Management posed significant challenges, including the need for broad-spectrum empirical antibiotic therapy and increasing antimicrobial resistance among Gemella isolates. Surgical intervention was frequently required for severe valvular dysfunction, persistent infection, or embolic complications. Despite advances in diagnosis and treatment, endocarditis due to  Gemella  species remains associated with significant morbidity and mortality, underscoring the importance of early recognition and multidisciplinary management. This review highlights the emerging clinical significance of Gemella species as causative agents of infective endocarditis and identifies areas for further research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gonzalez et al.)

Diabetic retinopathy (DR) is a leading cause of global visual impairment, necessitating a comprehensive understanding of its vascular and neural components for effective therapeutic interventions. While vascular pathology is well-established, recent evidence suggests a neurodegenerative role in DR. Vascular endothelial growth factor (VEGF), traditionally implicated in angiogenesis, has emerged as a key player with neuroprotective potential. This systematic review evaluates the literature to shed light on molecular mechanisms and clinical implications in this regard. The review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassing a thorough search strategy across multiple databases. Three in vitro studies met the inclusion criteria, highlighting the limited research in this evolving field. Findings suggest VEGF's neuroprotective effects on retinal ganglion cells (RGCs) and retinal neurons, unveiling potential therapeutic avenues. However, concerns arise regarding anti-VEGF therapies' impact on RGC survival. The review discusses the need for further research to delineate specific isoforms and signaling pathways responsible for VEGF-mediated neuroprotection. The delicate balance between angiogenesis and neuroprotection poses challenges in therapeutic development, emphasizing the importance of targeted interventions. Despite limitations, this review provides valuable insights into the intricate relationship between VEGF and neuroprotection in DR, paving the way for future investigations and redefining therapeutic strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Yadav et al.)

Single-molecule detection at a nanometric interface in a femtomolar solution, can take weeks as the encounter rate between the diffusing molecule to be detected and the transducing nanodevice is negligibly small. On the other hand, several experiments prove that macroscopic label-free sensors based on field-effect-transistors, engaging micrometric or millimetric detecting interfaces are capable to assay a single-molecule in a large volume within few minutes. The present work demonstrates why at least a single molecule out of a few diffusing in a 100 µL volume has a high probability to hit a large capturing and detecting electronic interface. To this end, sensing data, measured with an electrolyte-gated FET whose gate is functionalized with 10 12 capturing anti-immunoglobulin G, are here provided along with a Brownian diffusion-based modeling. The EG-FET assays solutions down to some tens of zM in concentrations with volumes ranging from 25 µL to 1 mL in which the functionalized gates are incubated for times ranging from 30 s to 20 min. The high level of accordance between the experimental data and a model based on the Einstein's diffusion-theory proves how the single-molecule detection process at large-capturing interfaces is controlled by Brownian diffusion and yet is highly probable and fast., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

This paper shows one of the few examples in the literature on the feasibility of novel materials from natural and biocompatible polymers like inulin (INU) or glycol chitosan (GCS) templated by the formation of o / w (inverse) high internal phase emulsion (HIPE). To the best of our knowledge, this is the first example of inverse polyHIPEs obtained from glycol chitosan or inulin. The obtained polyHIPEs were specifically designed for possible wound dressing applications. The HIPE (pre-crosslinking emulsion) was obtained as inverse HIPE, i.e., by forming a cream-like 80:20 v/v o / w emulsion by using the isopropyl myristate in its oil phase, which is obtained from natural sources like palm oil or coconut oil. The surfactant amount was critical in obtaining the inverse HIPE and the pluronic F127 was effective in stabilizing the emulsion comprising up to 80% v / v as internal phase. The obtained inverse HIPEs were crosslinked by UV irradiation for methacrylated INU or by glutaraldehyde-crosslinking for GCS. In both cases, inverse poly-HIPEs were obtained, which were physicochemically characterized. This paper introduces a new concept in using hydrophilic, natural polymers for the formation of inverse poly-HIPEs.

Paravertebral block, especially thoracic paravertebral block, is an effective regional anesthetic technique that can provide significant analgesia for numerous surgical procedures, including breast surgery, pulmonary surgery, and herniorrhaphy. The technique, although straightforward, is not devoid of potential adverse effects. Proper anatomic knowledge and adequate technique may help decrease the risk of these effects. In this brief discourse, we discuss the anatomy and technical aspects of paravertebral blocks and emphasize the importance of appropriate needle manipulation in order to minimize the risk of complications. We propose that, when using a landmark-based approach, limiting medial and lateral needle orientation and implementing caudal (rather than cephalad) needle redirection may provide an extra margin of safety when performing this technique. Likewise, recognizing a target that is not in close proximity to the neurovascular bundle when using ultrasound guidance may be beneficial.

Background: Adequate phonation is self-regulated by auditory feedback. Children with bilateral profound hearing loss (PHL) lack this feedback resulting in abnormal voice. Adequate hearing aid use and auditory-verbal therapy (AVT) may improve voice quality in deaf children., Objective: To study whether hearing aid use and AVT approach improve acoustic parameters of voice of children with bilateral PHL., Materials and Methods: Nineteen children with bilateral PHL were studied. Age range 2-5 years (X = 53.04 months; SD = 9.54). All children were fitted with hearing aids according to auditory testing and they underwent a 1-year auditory habilitation period using the AVT approach. Acoustic analysis of voice including F0, shimmer, and jitter was performed at the onset and at the end of the auditory habilitation period. Final acoustic data were compared to a matched control group of 19 children, age range 2-5 years (X = 52.85; SD = 9.74) with normal hearing., Results: Mean fundamental frequency (F0) was significantly increased after AVT intervention. Shimmer and jitter significantly (P < 0.05) improved after the intervention period. However, despite the improvements, mean F0 at the end of the intervention period was still significantly (P < 0.05) decreased as compared to controls. Also, mean shimmer and jitter at the end of the habilitation period were still significantly (P < 0.05) higher as compared to controls., Conclusions: The results of this preliminary study suggest that hearing aid use and auditory habilitation with AVT approach improved acoustic voice parameters of children with PHL. However, acoustic parameters persisted abnormal as compared to matched normal hearing controls. AVT approach and regular hearing aid use seem to be safe and reliable clinical tools for improving voice quality of children with PFL., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Summarize the current thinking concerning the clinically relevant aspects of nerve anatomy and best injection sites for nerve blocks., Recent Findings: The widespread use of ultrasound in regional anesthesia has changed the practice of regional anesthesia and created new possibilities. Among them is the ability to identify fascial planes, and this has become the basis for a new group of blocks, the fascial plane blocks. In this kind of blocks, the target for injection is the plane itself and not a nerve in particular. transversus abdominis plane, pectoralis muscles, erector spinae plane blocks are some examples of fascial blocks. Because injecting into a fascial plane is not controversial, these blocks are not included in our discussion of optimal placement of the needle.To determine optimal needle placement, it is important to have a clear definition of what constitutes intraneural. Although, there is almost universal agreement that the violation of the epineurium defines the intraneural concept, the literature include several studies where this assessment is erroneous.Although intentional intraneural injection is still considered objectionable, some literature suggests that injecting intraneurally, especially if extrafascicular, may be benign. This evidence is limited and anecdotal., Summary: It is necessary to have a better understanding of what intraneural injection is when dealing with any type of nerve blocks, be that single nerve, plexuses, or the sciatic nerve. Perineural injections provide successful anesthesia without putting the nerve integrity at risk. That practice is supported by years of experience and common sense. Currently, there is no evidence to support any kind of intraneural injections, intrafascicular or extrafascicular.

The popularity of ultrasound-guided nerve blocks has impacted the practice of regional anesthesia in profound ways, improving some techniques and introducing new ones. Some of these new nerve blocks are based on the concept of fascial plane blocks, in which the local anesthetic is injected into a plane instead of around a specific nerve. Pectoralis muscles (PECS) and serratus blocks, most commonly used for post op analgesia after breast surgery, are good examples. Among the nerves targeted by PECS/serratus blocks are different branches of the brachial plexus that traditionally have been considered purely motor nerves. This unsubstantiated claim is a departure from accepted anatomical knowledge and challenges our understanding of the sensory innervation of the chest wall. The objective of this Daring Discourse is to look beyond the ability of PECS/serratus blocks to provide analgesia/anesthesia of the chest wall, to concentrate instead on understanding the mechanism of action of these blocks and, in the process, test the veracity of the claim. After a comprehensive review of the evidence we have concluded that (1) the traditional model of sensory innervation of the chest wall, which derives from the lateral branches of the upper intercostal nerves and does not include branches of the brachial plexus, is correct. (2) PECS/serratus blocks share the same mechanism of action, blocking the lateral branches of the upper intercostal nerves, and so their varied success is tied to their ability to reach them. This common mechanism agrees with the traditional innervation model. (3) A common mechanism of action supports the consolidation of PECS/serratus blocks into a single thoracic fascial plane block with a point of injection closer to the effector site. In a nod to transversus abdominus plane block, the original inspiration for PECS blocks, we propose naming this modified block, the serratus anterior plane block., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Diltiazem hydrochloride, topically applied at 2% concentration, is considered effective for the treatment of chronic anal fissures, although it involves several side effects among which anal pruritus and postural hypotension. To test the hypothesis that a sustained delivery system of diltiazem hydrochloride may be helpful for the treatment of chronic anal fissures, in the present study we evaluated the potential of gels containing diltiazem hydrochloride entrapped in microsponges. Such microsponges were based on Eudragit RS 100 and the effect of some formulation variables was assessed by a 2 3 full factorial screening design. An optimized formulation of diltiazem hydrochloride microsponges was dispersed in Methylcellulose 2% or Poloxamer 407 20% and the resulting gels (micro-l-diltiazem hydrochloride 2%) were subjected to in vitro drug release, ex vivo permeability and drug deposition after application on porcine rectal mucosa. The results showed a prolonged release up to 24 h from micro-l-diltiazem hydrochloride at 2% in the gels. The permeation tests revealed up to 18% higher drug retention on the mucosal tissue after 24 h by the micro-l-diltiazem hydrochloride 2% gels compared to conventional diltiazem hydrochloride gels at 2%. These results suggest that diltiazem hydrochloride-loaded microsponges dispersed in rectal gels may be useful to overcome some limitations of conventional local chronic anal fissure therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The development of antibacterial coatings is of great interest from both industry and the consumer's point of view. In this study, we characterized tanned leather and polyurethane leatherette, typically employed in the automotive and footwear industries, which were modified by photo-deposition of antibacterial silver nanoparticles (AgNPs). Material surface chemical composition was investigated in detail by X-ray photoelectron spectroscopy (XPS). The material's antibacterial capability was checked against Escherichia coli and Staphylococcus aureus , as representative microorganisms in cross transmissions. Due to the presence of silver in a nanostructured form, nanosafety issues were considered, as well. Ionic release in contact media, as well as whole nanoparticle release from treated materials, were quantitatively evaluated, thus providing specific information on potential product nanotoxicity, which was further investigated through cytocompatibility MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays, also after surface abrasion of the materials. The proved negligible nanoparticle release, as well as the controlled release of antibacterial ions, shed light on the materials' potentialities, in terms of both high activity and safety., Competing Interests: The authors declare no conflict of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background and Objectives: The "stoplight" sign is a frequently described image during ultrasound-guided interscalene block, referring to 3 hypoechoic structures found between the anterior and middle scalene muscles.This study was designed to establish the ultrasound-anatomy correlation of this sign and to find any other anatomical features within the roots that could help with the interpretation of the ultrasound images obtained at the interscalene level., Methods: We performed 20 dissections of the brachial plexus in 10 embalmed human cadavers and systematically analyzed and measured the roots of C5 to C7 and then correlated these findings with ultrasonographic images on file., Results: We found that the C5 root is significantly smaller than either C6 or C7 (P < 0.0001). We also found that C6 and C7, but not C5, frequently present macroscopic evidence of intraroot splitting visible to the naked eye. We also found that the roots of C5 and C6, but not of C7, present frequent variations in their relationship with the scalene muscles., Conclusions: Our results provide the anatomic basis to define the stoplight sign as one made of, from cephalad to caudal, the root of C5, the upper fascicle(s) of C6, and the lower fascicle(s) of C6 without contribution from C7. The important clinical implication is that an injection attempted between what is commonly perceived as the gap between C6 and C7 would indeed be an intraneural injection at C6, which could potentially spread toward the neuraxial space.

Background and Objectives: Chronic knee pain is common in all age groups. Some patients who fail conservative therapy benefit from radiofrequency neurotomy. Knowledge of the anatomy is critical to ensure a successful outcome. The purpose of this study was to reanalyze the innervation to the anterior knee capsule from the perspective of the interventional pain practitioner., Methods: The study included a comprehensive literature review followed by dissection of 8 human knees to identify the primary capsular innervation of the anterior knee joint. Photographs and measurements were obtained for each relevant nerve branch. Stainless-steel wires were placed along the course of each primary innervation, and radiographs were obtained., Results: Literature review revealed a lack of consensus on the number and origin of nerve branches innervating the anterior knee capsule. All dissections revealed the following 6 nerves: superolateral branch from the vastus lateralis, superomedial branch from the vastus medialis, middle branch from the vastus intermedius, inferolateral (recurrent) branch from the common peroneal nerve, inferomedial branch from the saphenous nerve, and a lateral articular nerve branch from the common peroneal nerve. Nerve branches showed variable proximal trajectories but constant distal points of contact with femur and tibia. The inferolateral peroneal nerve branch was found to be too close to the common peroneal nerve, making it inappropriate for radiofrequency neurotomy., Conclusions: The innervation of the anterior capsule of the knee joint seems to follow a constant pattern making at least 3 of these nerves accessible to percutaneous ablation. To optimize clinical outcome, well-aligned radiographs are critical to guide lesion placement.

Background and Objectives: A femoral block sometimes fails to provide complete sensory anesthesia of the anterior aspect of middle and distal thigh, and a block of the lateral cutaneous nerve of the thigh (LCN) is often necessary to supplement it. The goal of this study was to demonstrate, both in the anatomy laboratory and in the clinical setting, a possible contribution of the LCN to the innervation of the anterior thigh., Methods: This was a prospective, observational study, including anatomic dissections and a clinical section in which 22 patients received an ultrasound-guided block of the LCN. The resulting area of anesthesia was determined 15 minutes later using pinprick examination., Results: In 1 of 3 thigh dissections, we found a dominant LCN innervating most of the anterior aspect of the middle and distal thigh, areas that are usually attributed to the femoral nerve. In the clinical part of the study, 10 patients (45.5%) developed an area of anesthesia that extended to the medial aspect of the thigh and distally to the patella., Conclusions: Our results, coming from a small sample, seem to indicate that the LCN may contribute to the innervation of the anterior thigh in some cases. A block of the LCN could be considered when a femoral block has failed to produce the expected area of anesthesia.

Two-dimensional (2D) ultrasound is commonly used for regional block of the axillary brachial plexus. In this technical case report, we described a real-time three-dimensional (3D) ultrasound-guided axillary block. The difference between 2D and 3D ultrasound is similar to the difference between plain radiograph and computer tomography. Unlike 2D ultrasound that captures a planar image, 3D ultrasound technology acquires a 3D volume of information that enables multiple planes of view by manipulating the image without movement of the ultrasound probe. Observation of the brachial plexus in cross-section demonstrated distinct linear hyperechoic tissue structures (loose connective tissue) that initially inhibited the flow of the local anesthesia. After completion of the injection, we were able to visualize the influence of arterial pulsation on the spread of the local anesthesia. Possible advantages of this novel technology over current 2D methods are wider image volume and the capability to manipulate the planes of the image without moving the probe.

Brachial plexus blockade is the cornerstone of the peripheral nerve regional anesthesia practice of most anesthesiologists. As part of the American Society of Regional Anesthesia and Pain Medicine's commitment to providing intensive evidence-based education related to regional anesthesia and analgesia, this article is a complete update of our 2002 comprehensive review of upper extremity anesthesia. The text of the review focuses on (1) pertinent anatomy, (2) approaches to the brachial plexus and techniques that optimize block quality, (4) local anesthetic and adjuvant pharmacology, (5) complications, (6) perioperative issues, and (6) challenges for future research.

Background and Objectives: This review of articles summarizes recent developments in relation to fat located in the epidural space and also in dural sleeves of spinal nerve roots in order to improve our understanding of the clinical effects of the epidural blockade., Method: Medline search was carried cross-matching of the following words: "epidural fat", "epidural space", "adipose tissue" and "fat cells" from 1966 to 2008 in which articles referring to different pathologies that alter the epidural fat were also reviewed. Techniques used by different authors included the use of samples from dissections, cryomicrotome sections, as well as light and electron microscopy., Results: Fat in the epidural space has a metameric distribution along the spinal canal that can be altered in some pathological conditions. Epidural fat is not evenly distributed. At cervical level fat is absent while in the lumbar region, fat in the anterior and posterior aspects of the epidural space forms two unconnected structures. Fat cells are found also in the thickness of dural sleeves enveloping spinal nerve roots but not in the region of the dural sac. Epidural lipomatosis is characterized by an increase in epidural fat content. When a patient has a combination of kyphosis and scoliosis of the spine, the epidural fat distributes asymmetrically. Spinal stenosis is frequently accompanied by a reduction in the amount of epidural fat around the stenotic area., Conclusions: The epidural space contains abundant epidural fat that distributes along the spinal canal in a predictable pattern. Fat cells are also abundant in the dura that forms the sleeves around spinal nerve roots but they are not embedded within the laminas that form the dura mater of the dural sac. Drugs stored in fat, inside dural sleeves, could have a greater impact on nerve roots than drugs stored in epidural fat, given that the concentration of fat is proportionally higher inside nerve root sleeves than in the epidural space, and that the distance between nerves and fat is shorter. Similarly, changes in fat content and distribution caused by different pathologies may alter the absorption and distribution of drugs injected in the epidural space.

Background and Objectives: In 2003 we introduced the concept of a sciatic nerve block performed in the midgluteal area at a fixed distance from the midline in all adults regardless of gender and/or body size. The anatomic basis for that study suggested that a subgluteal block could also be accomplished in a similar fashion., Methods: After informed consent, 20 patients were prospectively recruited. Patients were positioned in lateral decubitus. The needle insertion site was located in the subgluteal fold at 10 cm from the midline. The needle was advanced parallel to the midline until a sciatic nerve response was elicited. With a visible response at 0.5 mA, 30 mL 1.5% mepivacaine plus 1:200,000 epinephrine was slowly injected. Sensory anesthesia was tested on the plantar and dorsal aspects of the foot as well as the posterior thigh., Results: Residents performed all blocks. The approach was 100% successful in locating the sciatic nerve with 3 attempts or less from a site located 10 cm from the midline. The block provided successful surgical anesthesia in 90% of the cases; 2 cases required local anesthetic supplementation. Only 3 patients developed anesthesia of the posterior thigh within 30 minutes of injection., Conclusions: This report shows that a sciatic nerve block can be performed in the subgluteal area at 10 cm from the midline in adult patients of both sexes and various sizes. Anesthesia of the posterior thigh is not consistently accomplished with this approach.

Regional anesthesia in the obese patient can be challenging and possibly carries a greater failure rate as compared with that in the non-obese patient. We retrospectively reviewed our prospectively gathered peripheral block data to determine the influence of body weight on success rate of the supraclavicular block. Obesity was defined as body mass index > or =30. The overall success rate was 97.3% in nonobese and 94.3% in obese patients (P < 0.01). Residents completed 80% of the blocks in nonobese patients and 73% in obese patients (P < 0.01). No difference in acute complications was observed. Obesity is associated with a slight decrease in success rate of supraclavicular block and an increase in its relative difficulty without apparent effect on acute complications.

Unlabelled: Portable nerve stimulators for nerve blocks have been available for more than 40 yr. It is generally accepted that seeking a motor response at low outputs increases the chances of success. It is customary to start the procedure at a higher current with the goal of finding the nerve. After an adequate response is elicited, the current is decreased before the local anesthetic is injected. However, how low is low enough and, for that matter, how high is too high have not been adequately determined. Our experience seems to indicate that, in the supraclavicular block, the type of response obtained is as important as the output at which it is elicited, provided that this current is not higher than 1 mA. In this context, it is theoretically possible that our initial seeking current of 0.9 mA could be an adequate injection current if it is combined with an appropriate response. We designed this study to test the hypothesis that a response of the fingers in flexion or extension, elicited at 0.9 mA, could be followed immediately by the local anesthetic injection. We did not intend to compare 0.5 and 0.9 mA as minimum stimulating currents but rather as currents able to elicit an unmistakable motor twitch. Sixty patients were randomly assigned to one of two groups. Group 1 (n = 30) was injected with a motor twitch in the fingers that was still visible at 0.5 mA. Group 2 (n = 30) was injected after a similar response to that in Group 1 was elicited, but at the initial output of 0.9 mA, without any further decrease. The blocks were injected with 40 mL of local anesthetic solution. One patient was excluded from the study for failing to meet protocol criteria. The success rate in the remaining 59 patients was 100%; success was defined as complete sensory blockade at the median, ulnar, and radial nerve territories of the hand that was accomplished in

Constrictive arterial remodeling accounts for a significant proportion of lumen loss in atherosclerotic progression and postangioplasty stenosis. Recent research suggests that constrictive remodeling is mediated by turnover of the extracellular matrix. We hypothesized that remodeling could be attenuated by treatment with the safe, effective matrix metalloproteinase (MMP) inhibitor doxycycline. Female rabbit abdominal aortas were denuded using a 4-Fr balloon embolectomy catheter, and reinjured 3 weeks later. Treatment with 30 mg/kg/day doxycycline was begun the day before the second injury. At 6 weeks after injury, lumen area measured 13.1 +/- 1.2 mm(2) in controls compared to 17.5 +/- 1.6 mm(2) in doxycycline-treated rabbits (p = 0.05). At 4 days after injury, MMP-2 activity was increased compared to uninjured controls, but doxycycline treatment reduced MMP-2 activity. Doxycycline treatment also inhibited fibrillar collagen deposition in the intima by 87% as detected by polarized light microscopy. Doxycycline was an effective inhibitor of constrictive arterial remodeling in the rabbit aorta. Treatment reduced MMP activity and attenuated the deposition of extracellular matrix particularly in the intima., (Copyright 2004 S. Karger AG, Basel)

Unlabelled: Bilateral regional anesthesia techniques in general and bilateral brachial plexus blocks in particular are rarely performed because they have few clinical indications. We present the case of a patient who presented to the operating room for bilateral upper extremity procedures where we thought regional anesthesia was appropriate. The anesthesia management is discussed as well as potential problems and complications., Implications: Reports on bilateral regional blocks are extremely rare in the literature. Whereas they have the potential for more complications than a single technique, they can be very useful in specific clinical situations.

Recent research has shown that the tetracycline antibiotics are pluripotent drugs that inhibit the activity of matrix metalloproteinases (MMPs) and affect many cellular functions including proliferation, migration, and matrix remodeling. We have shown that doxycycline inhibits MMP activity and intimal thickening after injury of the rat carotid artery, however we do not know whether these effects are because of the antibiotic, anti-MMP, or other actions of doxycycline. Recently, chemically modified tetracyclines have been synthesized that lack antibiotic activity but retain anti-MMP activity (CMT-3), or lack both antibiotic and anti-MMP activity (CMT-5). In the current study we have assessed the effects of treatment with CMT-3 or CMT-5 on intimal thickening after balloon catheter injury of the rat carotid artery. Rats were treated by oral gavage with 15 mg/kg/day CMT-3 or CMT-5. CMT-3 significantly reduced smooth muscle cell (SMC) proliferation in both the medial and intimal layers of the injured rat carotid artery compared to CMT-5. Furthermore, CMT-3 inhibited SMC migration from the media to the intima by 86% at 4 days after injury. CMT-3 also decreased MMP-2 activity. Finally, we found that CMT-3 treatment resulted in a significant reduction in intimal cross-sectional area from 0.23 +/- 0.01 mm(2) in the CMT-5 control group to 0.19 +/- 0.01 mm(2). There was also a reduction in elastin and collagen accumulation within the intima. We conclude that CMT-3 attenuated intimal thickening after arterial injury by inhibiting SMC proliferation, migration and MMP activity, and accumulation of extracellular matrix. The inhibitory effects of CMT-3 were independent of the antibiotic properties, but were dependent on the anti-MMP activity of the tetracycline family.

The collagen matrix constitutes a major portion of the vascular extracellular matrix and imparts blood vessels with tensile strength and, even more important, modulates smooth muscle cell (SMC) responses via specific receptors and signaling pathways. This review is focused on the interactions of SMCs with the collagen matrix, how these interactions are involved in sensing the local environment, and the receptors that mediate these processes. Better understanding of the pathways involved in cell matrix interactions promises to provide novel therapeutic targets and treatment strategies for the prevention of arterial occlusive diseases such as atherosclerosis and restenosis.

Background and Objectives: Buprenorphine added to local anesthetic solutions for supraclavicular block was found to triple postoperative analgesia duration in a previous study when compared with local anesthetic block alone. That study, however, did not control for potentially confounding factors, such as the possibility that buprenorphine was affecting analgesia through intramuscular absorption or via a spinal mechanism. To specifically delineate the role of buprenorphine in peripherally mediated opioid analgesia, the present study controlled for these 2 factors., Methods: Sixty American Society of Anesthesiologists (ASA) P.S. I and II, consenting adults for upper extremity surgery, were prospectively assigned randomly in double-blind fashion to 1 of 3 groups. Group I received local anesthetic (1% mepivacaine, 0.2% tetracaine, epinephrine 1:200,000), 40 mL, plus buprenorphine, 0.3 mg, for axillary block, and intramuscular (IM) saline. Group II received local anesthetic-only axillary block, and IM buprenorphine 0.3 mg. Group III received local anesthetic-only axillary block and IM saline. Postoperative pain onset and intensity were compared, as was analgesic medication use., Results: The mean duration of postoperative analgesia was 22.3 hours in Group I; 12.5 hours in group II, and 6.6 hours in group III. Differences between groups I and II were statistically significant (P =.0012). Differences both between groups I and III and II and III were also statistically significant (P <.001)., Conclusions: Buprenorphine-local anesthetic axillary perivascular brachial plexus block provided postoperative analgesia lasting 3 times longer than local anesthetic block alone and twice as long as buprenorphine given by IM injection plus local anesthetic-only block. This supports the concept of peripherally mediated opioid analgesia by buprenorphine.

Background and Objectives: Over the past 10 years, several studies have suggested that the addition of certain opiates to the local anesthetic used for brachial block may provide effective, long-lasting postoperative analgesia. One of these studies indicated that the agonist-antagonist, buprenorphine, added to bupivacaine provided a longer period of postoperative analgesia than the traditional opiates, but in this study, it is impossible to determine the relative contributions of the local anesthetic and the opiate to the postoperative analgesia because of the extremely long duration of the anesthesia provided by the local anesthetic, bupivacaine. By repeating the study using a local anesthetic of a shorter duration, the present study delineates more clearly the contribution of the buprenorphine to postoperative analgesia when added to a shorter-acting local anesthetic., Methods: Forty, healthy, consenting adult patients scheduled for upper extremity surgery were enrolled in the study. Premedication was provided by intravenous midazolam 2 mg/70 kg and anesthesia by a subclavian perivascular brachial plexus block. The patients were assigned randomly to 1 of 2 equal groups based on the agents used for the blocks. The patients in group I received 40 mL of a local anesthetic alone, while those in group II received the same local anesthetic plus buprenorphine 0.3 mg. The study was kept double-blind by having 1 anesthesiologist prepare the solutions, a second anesthesiologist perform the blocks, and a third anesthesiologist monitor the anesthesia and analgesia thereafter, up to and including the time of the first request for an analgesic medication. The data were reported as means (+/- SEM), and differences between groups were determined using repeated measures of analysis of variance (ANOVA) and chi(2), followed by the Fisher exact test for post hoc comparison. A P value of less than.05 was considered to be statistically significant., Results: The mean duration of postoperative pain relief following the injection of the local anesthetic alone was 5.3 (+/- 0.15) hours as compared with 17.4 (+/- 1.26) hours when buprenorphine was added, a difference that was statistically (and clinically) significant (P <.0001)., Conclusions: The addition of buprenorphine to the local anesthetic used for brachial plexus block in the present study provided a 3-fold increase in the duration of postoperative analgesia, with complete analgesia persisting 30 hours beyond the duration provided by the local anesthetic alone in 75% of the patients. This practice can be of particular benefit to patients undergoing ambulatory upper extremity surgery by providing prolonged analgesia after discharge from the hospital.

Background and Objectives: Among the supraclavicular approaches to the brachial plexus, the subclavian perivascular technique is a well-established method of anesthesia of the upper extremity. Ever since Kulenkampf described his technique, eliciting a paresthesia has been almost mandatory ("no paresthesia, no anesthesia"). Lately, nerve stimulators have become more popular. However, up to the present time, clinical studies involving the nerve stimulator have failed to show success rates comparable to paresthesia techniques., Methods: Data from 1,001 consecutive, subclavian perivascular blocks were prospectively gathered over 2.5 years. All blocks were performed according to Winnie's technique, but using a nerve stimulator instead of a paresthesia. When an adequate response was obtained, 35 to 40 mL of local anesthetic solution was injected., Results: Nine hundred seventy-three blocks (97.2%) were completely successful; 16 blocks (1.6%) were incomplete and needed supplementation; and 12 blocks (1.2%) failed and required general anesthesia, giving a success rate for regional anesthesia of 98.8%., Conclusions: The subclavian perivascular block consistently provides an effective block for surgery on the upper extremity. At the site of injection with this technique, the plexus is reduced to its smallest components and the sheath is reduced to its smallest volume, which explains in great part the success obtained with this block. We believe that we have demonstrated a nerve stimulator technique that is both highly successful and safe; no clinical pneumothorax was found nor did any other major complications develop.

The intragenomic location of the elements of the I, G, jockey, F, and Doc transposon families has been studied by the Southern blot analysis, in 12 laboratory Drosophila melanogaster stocks. Elements located in euchromatin, heterochromatin, and on the Y chromosome are identified, and their stability has been assessed by comparing the autoradiographs detected in different stocks and analysis of individual flies. Evidence is shown suggesting that preferential location in euchromatin or heterochromatin and the distribution within heterochromatin are distinctive of transposon families. Elements located in heterochromatin can be unstable. These results are discussed in the context of the relationship between transposable elements and the host genome.

Background: A significant number of vascular injuries occur with the use of percutaneous diagnostic and therapeutic procedures. This study was done to indicate the types of these injuries and their management., Methods: Over a 30-month period, 55 patients required operation for vascular complications after percutaneous femoral procedures including infrarenal arteriography (six patients) and angioplasty (22 patients), coronary angiography (16 patients) and angioplasty (five patients), and aortic balloon pump insertion (six patients)., Results: The 14 iliac and 41 femoral artery injuries included 29 pseudoaneurysms, six lacerations with persistent bleeding, seven dissections, six occlusions, three ruptures, two arteriovenous fistulas, and two large hematomas. Control for all femoral and distal external iliac artery lesions was obtained solely through a groin incision in 45 (82%) patients. Our technique for exposure of the external iliac artery through the groin is described. A separate retroperitoneal incision was necessary in 10 patients because of proximal injury, massive pseudoaneurysm, morbid obesity, or heavily scarred groins. In this series 34 lateral suture repairs, 11 interposition or bypass grafts, four patch angioplasties, one endarterectomy, three thrombectomies, and two hematoma evacuations were performed. Although no limb loss occurred, we encountered nine wound complications, five myocardial infarctions, and two deaths., Conclusions: This experience shows the wide variety of vascular complications caused by percutaneous procedures and the different techniques necessary for their management.

Transcutaneous oxygen (TcPO2) measurement has proven to be an accurate means of predicting healing of ischemic wounds. This study compares the ability of TcPO2 and laser Doppler, modified by the addition of a heated probe (LDHP), to assess wound outcome. TcPO2 and LDHP measurements were made at the same site for 80 wounds, which consisted of 51 amputations (25 above knee, 6 below knee, 20 forefoot) and 29 ulcerations. Healing was defined as complete wound closure. Failure to heal was defined by the necessity for proximal amputation in 22 wounds (6 amputations, 16 ulcers). Outcome criteria were chosen to maximize accuracy and either positive or negative predictive values. Criteria with the greatest accuracy and positive predictive value for wound healing were > or = 11 mmHg for TcPO2 and > or = 50 mv for LDHP range. Criteria with the most appropriate accuracy and negative predictive value for wound failure were < 5 mmHg for TcPO2 and < 35 mv LDHP range. All wounds whose LDHP range was < 35 mv failed to heal, whereas some wounds with a TcPO2 of 0-1 mmHg healed successfully. An absolute prediction of wound healing (100% specificity and negative predictive value) was offered when either LDHP range was > or = 125 mv or TcPO2 was > or = 33 mmHg, although accuracy of either measurement at this criteria was unacceptable for more general application. We conclude that TcPO2 or LDHP will assess wound outcome with similar overall accuracy, although each test may be better for predicting a specific outcome.

Superoxide anion (O2-) and polymorphonuclear leukocytes (PMNs) have been implicated in the genesis of skeletal muscle ischemia-reperfusion (I-R) injury, but the source of (O2-) has not been established. We studied PMNs as a potential source of O2- using a ferricytochrome reduction assay in 5 anesthetized dogs. Using a gracilis muscle model of I-R, 6 hours of ischemia was followed by 2 hours of reperfusion. The contralateral muscle served as control. Prior to ischemia and after 0.5 and 2.0 hours of reperfusion, PMNs were separated from the gracilis venous effluent of ischemic (I) and control (C) muscles. Central venous samples were also obtained prior to surgical preparation and after reperfusion. Assays for O2- were performed with and without zymosan (Z) activation. Results are expressed as nmol O2-/2 x 10(6) PMNs +/- SEM. Baseline production of O2- was 0.49 +/- 0.54 in central venous samples; Z increased the values to 6.77 +/- 2.13. After 2 hrs of reperfusion, central O2- was 1.57 +/- 0.75, which increased to 7.1 +/- 1.04 with Z. Gracilis venous samples O2- values with and without Z are reported in Table I. One way measures of analysis of variance showed no significant (p > 0.05) differences between samples. Our results demonstrate that PMNs are not the sole source of O2- in the pathophysiology of skeletal muscle I-R injury. PMN associated injury may be mediated by mechanisms other than O2- production.