Infectious meningitis. Why are the leptomeninges preferentially involved? Electron microscopic insights.

In infectious meningitis, pathogens preferentially attack the leptomeninges (pia mater and arachnoid) rather than the pachymeninges (dura mater). This study aims to provide ultra-anatomical insights from our extensive collection of electron microscopy images and propose mechanisms, highlighting structures that favor the introduction, adherence, colonization, and proliferation of microorganisms leading to spinal meningitis. Over several years, we analyzed an extensive collection of transmission and scanning electron microscopy images of human spinal meninges captured in our laboratories. Upon examining 378 of those images, we identified potential sites for the iatrogenic or hematogenic introduction and adherence of microorganisms, as well as sites for their colonization and proliferation. These included the outer surface of the spinal dural sac, structures within the epidural space, and the spinal dural sac itself, which comprises compact dura mater with interwoven collagen fibers and tightly bound arachnoid cells. Also, the subdural (extra-arachnoid) compartment, consisting of fragile neurothelial cells prone to rupture under force, formed an acquired spinal subdural space, a new subarachnoid compartment, limited by arachnoid trabeculae, that surrounded the nerve roots and spinal cord and the pia mater. Macrophages, fibroblasts, mast cells, and plasma cells were also observed within the dura mater, arachnoid layer, arachnoid trabeculae, and pia mater. These images illustrate how the characteristics of the meningeal layers could contribute to bacterial adhesion and proliferation at various locations, inducing selective inflammation during (iatrogenic) spinal meningitis. In addition, the images help to explain why magnetic resonance imaging enhancement appears preferentially at specific sites.

Identification of spread after deliberated intraneural injection in five mammalian species: not all animal models and needle types are valid for studying the effect of intraneural injections in humans.

INTRODUCTION: This research endeavors to investigate the phenomenon of intraneural spread across distinct locations: subcircumneurium, extrafascicular intraneural, intrafascicular intraneural, and intraperineurium after deliberate intraneural injections across five mammalian species. The study also aims to propose determinants influencing this spread. Furthermore, the investigation strives to ascertain the optimal animal species and needle configuration for extrapolating intraneural injection outcomes to human contexts. METHODS: This study examined 60 sciatic nerves from 30 fresh and untreated cadavers of rats, rabbits, dogs, pigs, and sheep. The specimens were organized into five groups, each comprising an equal number of nerves. Histological assessments were performed on 30 nerves, involving fascicle metrics. The remaining 30 nerves underwent intentional intraneural injections, facilitated by 19G and 23G needles under ultrasound and direct visualization guidance.Heparinized erythrocytes combined with a methylene blue solution were used as a marker to analyze the extent and patterns of intraneural spread. Needle orifice measurements were obtained, and these data were overlaid onto images of both nerves and needles. This enabled a comparative evaluation of sizes and an assessment of marker diffusion. RESULTS: The findings indicated that sciatic nerves in rats, rabbits, and dogs were oligofascicular, characterized by larger fascicles, whereas pigs and sheep exhibited polyfascicular nerves comprised of numerous smaller fascicles. Fascicular diameters were variable across species, with dogs presenting the largest measurements. While intraneural spread was observed and documented, intrafascicular marker spreading was rare, occurring only in one rabbit specimen. Needle orifice attributes were scrutinized and visually depicted. CONCLUSIONS: Despite the formidable challenges associated with the practical realization of intrafascicular injection, the utilization of animal models possessing monofascicular or oligofascicular nerves, such as rats, rabbits, and dogs, in conjunction with needles featuring aperture dimensions surpassing those of the fascicles, likely contributes to the compromised reliability of investigations into intraneural injection outcomes.

Feasibility of a brief mindfulness-based program for burnout in pain healthcare professionals.

Introduction: Stress inherent to health care, which is characterized by work overload and shortage of specialized staff, is associated with decreased quality of life and suboptimal patient care. Mindfulness-based programs have proved to be effective in reducing stress in healthcare providers. This study aims to assess the feasibility of an 8-week mindfulness program to reduce the burnout levels of the staff of a pain clinic in a tertiary public hospital. Materials and methods: A longitudinal study with a within subject pre/post-intervention design, consisting of daily face-to-face 10-min sessions and the creation of a virtual group using a social media platform. Variables measured: burnout, mindfulness, empathy, self-compassion, and demographic characteristics. Results: Program feasibility (i.e., reach, adherence, acceptability, and preliminary effectiveness) was evaluated in 10 participants (6 physicians, 2 nurse practitioners, 1 nursing assistant, and 1 administrative). The results revealed a high reach (i.e., participation rate of 90%), excellent adherence to the program (daily practice 95% of times), and very good acceptability of the group format and satisfaction with most treatment components. Regarding potential effectiveness, we report the results of the Wilcoxon signed-rank tests and its associated effect size (r). We observed improvements in mindfulness and all its subscales (-2.077 ≤ Z ≤ -2.703, 0.69 ≤ r ≤ 0.90, all p < 0.05) except for non-reactivity and all subcomponents of self-compassion (-2.501 ≤ Z ≤ -2.611, 0.83 ≤ r ≤ 0.87, all p < 0.05) but not on its global self-compassion score. Empathy and burnout did not change. In an exploratory manner, however, we found significant reductions in the burnout component of emotional exhaustion, but only in physicians (Z = -2.201, p = 0.028, r = 0.73). Discussion: We believe that the 8-week mindfulness-based program described in the present investigation might be a feasible and potentially effective method that can be easily implemented to reduce burnout and promote mindfulness in specialized pain clinics.

Visceral versus somatic pain: an educational review of anatomy and clinical implications.

Somatic and visceral nociceptive signals travel via different pathways to reach the spinal cord. Additionally, signals regulating visceral blood flow and gastrointestinal tract (GIT) motility travel via efferent sympathetic nerves. To offer optimal pain relief and increase GIT motility and blood flow, we should interfere with all these pathways. These include the afferent nerves that travel with the sympathetic trunks, the somatic fibers that innervate the abdominal wall and part of the parietal peritoneum, and the sympathetic efferent fibers. All somatic and visceral afferent neural and sympathetic efferent pathways are effectively blocked by appropriately placed segmental thoracic epidural blocks (TEBs), whereas well-placed truncal fascial plane blocks evidently do not consistently block the afferent visceral neural pathways nor the sympathetic efferent nerves. It is generally accepted that it would be beneficial to counter the effects of the stress response on the GIT, therefore most enhanced recovery after surgery protocols involve TEB. The TEB failure rate, however, can be high, enticing practitioners to resort to truncal fascial plane blocks. In this educational article, we discuss the differences between visceral and somatic pain, their management and the clinical implications of these differences.

Telemonitoring in Chronic Pain Management Using Smartphone Apps: A Randomized Controlled Trial Comparing Usual Assessment against App-Based Monitoring with and without Clinical Alarms.

BACKGROUND: The usefulness of mHealth in helping to target face-to-face interventions for chronic pain more effectively remains unclear. In the present study, we aim to test whether the Pain Monitor mobile phone application (app) is well accepted by clinicians, and can help improve existent medical treatments for patients with chronic musculoskeletal pain. Regarding this last goal, we compared three treatment conditions, namely usual treatment, usual treatment with an app without alarms and usual treatment with an app with alarms. All treatments lasted one month. The three treatments were compared for all outcomes, i.e., pain severity and interference, fatigue, depressed mood, anxiety and anger. METHODS: In this randomized controlled trial, the usual monitoring method (i.e., onsite; n = 44) was compared with daily ecological momentary assessment using the Pain Monitor app-both with (n = 43) and without alarms (n = 45). Alarms were sent to the clinicians in the presence of pre-established undesired clinical events and could be used to make treatment adjustments throughout the one-month study. RESULTS: With the exception of anger, clinically significant changes (CSC; 30% improvement) were greater in the app + alarm condition across outcomes (e.g., 43.6% of patients experienced a CSC in depressed mood in the app + alarm condition, which occurred in less than 29% of patients in the other groups). The clinicians were willing to use the app, especially the version with alarms. CONCLUSIONS: The use of apps may have some benefits in individual health care, especially when using alarms to tailor treatments.

A novel marker for identifying and studying the membranes, barriers, and compartments surrounding peripheral nerves microscopically.

Recent anatomical discoveries indicate the importance of identifying membranes and compartments surrounding peripheral nerves into which local anesthetic agents can be injected and continuous nerve block catheters placed during regional anesthetic procedures. However, current markers used in anatomical studies have multiple drawbacks, specifically extravasation into noninjected locations, which can result in inadequate treatment. We studied a readily-available new marker, heparinized blood solution (HBS), which is easy to identify by microscopy and can remain in the nerve compartment into which it is deposited without distorting the tissue. We collected blood from 22 patients and prepared it as HBS. This was then injected into four fresh cadavers as in routine clinical practice for ultrasound-guided nerve blocks to form a so-called "doughnut" by "hydro-dissecting" at 32 sites. All samples, including nerves and neighboring tissues, were then prepared and examined by light microscopy. Although no deliberate intraneural injection was attempted, the marker was identified inside all the nerve compartments except the fascicles. Apart from leaking through the needle entry site in some instances, there was no extravasation of the HBS into neighboring nerve compartments in either direction. The tissues were not distorted and the erythrocytes did not form a thrombus. Nerve membranes and compartments could be clearly identified with routine staining. This technique enabled us to study the longitudinal and circumferential spread in all nerve compartments and to collect data for better interpretation of factors influencing an anesthetic nerve block and situations in which complications could possibly arise. HBS seemed superior to other markers because it did not leave the compartments into which it had been injected, did not distort the tissue, and was easily visible under the light microscope. Clin. Anat., 31:1050-1057, 2018. © 2018 Wiley Periodicals, Inc.

Microanatomical Nerve Architecture of 6 Mammalian Species: Is Trans-Species Translational Anatomic Extrapolation Valid?

BACKGROUND AND OBJECTIVES: Various animal models have historically been used to study iatrogenic nerve injury during performance of conduction nerve blocks. Our aims were to compare the microstructures of nerves in commonly used species to those of humans and to explore the validity of the extrapolating these findings to humans. METHODS: High-resolution, light-microscopic images were obtained from cross sections of sciatic nerves at their bifurcation from fresh rat, rabbit, pig, sheep, dog, and human cadavers. Various microanatomical characteristics were measured and compared between the species. P < 0.0033 indicated significant differences. RESULTS: Forty-four samples were studied. There were some interspecies similarities, but the majority of the microanatomical measurements of all 5 species differed significantly from those of humans. Exceptions were rat fascicle cross-sectional area (P = 0.367) and fascicle circumference (P = 0.396); ratio of dog, pig, and sheep fascicle area to total nerve area (dog: P = 0.350; pig: P = 0.958; sheep: P = 0.052); and number of fascicles (pig: P = 0.454; sheep P = 0.077). CONCLUSIONS: Although some of the metrics could reasonably be expected to differ because of the size of the species-for example, nerve cross-sectional area-there was little microanatomical similarity between the sciatic nerves of humans and those of the nonprimate mammalian species studied. This may question the validity of some conclusions reached over the years by direct translation from these species to humans. Further studies on nerve function, intraneural injection, and microanatomy of nonhuman primate species are warranted.

Improving pain treatment with a smartphone app: study protocol for a randomized controlled trial.

BACKGROUND: Chronic pain has become a major health problem across the world, especially in older adults. Unfortunately, the effectiveness of medical interventions is modest. Some have argued that assessment strategies should be improved if the impact of medical interventions is to be improved. Ecological momentary assessment using smartphones is now considered the gold standard in monitoring in health settings, including chronic pain. However, to the best of our knowledge, there is no randomized controlled trial to show that telemonitoring using a smartphone app can indeed improve the effectiveness of medical treatments in adults with chronic pain. The goal of this study will be to explore the effects of using a smartphone app for telemonitoring adults with chronic pain. METHODS: The study will be a randomized controlled trial with three groups: treatment as usual (TAU), TAU+app, and TAU+app+alarms. All groups will receive the adequate treatment for their pain, which will be prescribed the first day of study according to clinical guidelines. Assessment in the TAU group will be the usual at the Pain Clinic, that is, a paper-and-pencil evaluation at the onset of treatment (beginning of study) and at follow up (end of study, 30 days later). The other two groups (TAU+app and TAU+app+alarms) will be assessed daily using Pain Monitor, a smartphone app developed by our multidisciplinary team. Telemonitoring will only be made in the TAU+app+alarms group. For this group, physicians at the Pain Clinic may decide to adjust pain treatment in response to alarms. Telemonitoring is not the usual practice at the Pain Clinic and will not occur in the other two groups (TAU and TAU+app), so no changes in treatment are expected in these groups after the first appointment. The total sample size will be 150, with 50 patients in each group. The assessment protocol will be the same in all groups and will include pain intensity and side effects of the medication (primary outcomes), together with several pain-related variables like pain interference, activity level, use of rescue medication, pain catastrophizing, and pain acceptance, among others. DISCUSSION: We believe that the present trial has important clinical implications. We think that telemonitoring using ecological momentary assessment is crucial to improve current interventions for pain. The armamentarium of available treatments for pain is large, so physicians can turn to different treatments or dosages in the presence of an undesired event. The use of the app for telemonitoring can allow for this rapid detection of unwanted events, thus improving patient safety (i.e., withdrawal of treatment causing side effects) and augmenting treatment effectiveness (i.e., changing an ineffective treatment or dosage). In a time when smartphones are a mainstream technology, we should take advantage of them in the promotion of health care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03247725 . Registered on 25 July 2017.

An ultrasound-guided technique for axillary brachial plexus nerve block in rabbits.

Regional anesthesia techniques, such as nerve blocks, are routinely used in humans and can contribute to multimodal approaches to pain management in research animals. Ultrasound guidance is an emerging aspect of regional anesthesia that has the potential to optimize local delivery and distribution of anesthetic agents, thereby reducing the amounts of these agents that must be administered. The authors developed an ultrasound-guided technique for effective block of the axillary brachial plexus in rabbits. They used this technique to carry out nerve block in 14 rabbits. The procedure was accomplished in a relatively short amount of time and achieved successful nerve block in all rabbits with no adverse effects. Sonographic visualization of the distribution of the local anesthetic ropivacaine led to administration of smaller anesthetic doses in eight of the rabbits without affecting the duration of nerve block. The authors conclude that their technique is feasible and safe and provides effective analgesia of the thoracic limb in rabbits. They recommend that this technique be integrated into multimodal approaches to pain management in rabbits undergoing thoracic limb surgery.