Spatiotemporal Distribution of Electrically Evoked Spinal Compound Action Potentials During Spinal Cord Stimulation.

OBJECTIVES: Recent studies using epidural spinal cord stimulation (SCS) have demonstrated restoration of motor function in individuals previously diagnosed with chronic spinal cord injury (SCI). In parallel, the spinal evoked compound action potentials (ECAPs) induced by SCS have been used to gain insight into the mechanisms of SCS-based chronic pain therapy and to titrate closed-loop delivery of stimulation. However, the previous characterization of ECAPs recorded during SCS was performed with one-dimensional, cylindrical electrode leads. Herein, we describe the unique spatiotemporal distribution of ECAPs induced by SCS across the medial-lateral and rostral-caudal axes of the spinal cord, and their relationship to polysynaptic lower-extremity motor activation. MATERIALS AND METHODS: In each of four sheep, two 24-contact epidural SCS arrays were placed on the lumbosacral spinal cord, spanning the L3 to L6 vertebrae. Spinal ECAPs were recorded during SCS from nonstimulating contacts of the epidural arrays, which were synchronized to bilateral electromyography (EMG) recordings from six back and lower-extremity muscles. RESULTS: We observed a triphasic P1, N1, P2 peak morphology and propagation in the ECAPs during midline and lateral stimulation. Distinct regions of lateral stimulation resulted in simultaneously increased ECAP and EMG responses compared with stimulation at adjacent lateral contacts. Although EMG responses decreased during repetitive stimulation bursts, spinal ECAP amplitude did not significantly change. Both spinal ECAP responses and EMG responses demonstrated preferential ipsilateral recruitment during lateral stimulation compared with midline stimulation. Furthermore, EMG responses were correlated with stimulation that resulted in increased ECAP amplitude on the ipsilateral side of the electrode array. CONCLUSIONS: These results suggest that ECAPs can be used to investigate the effects of SCS on spinal sensorimotor networks and to inform stimulation strategies that optimize the clinical benefit of SCS in the context of managing chronic pain and the restoration of sensorimotor function after SCI.

Definitions for Loss of Domain: An International Delphi Consensus of Expert Surgeons.

BACKGROUND: No standardized written or volumetric definition exists for 'loss of domain' (LOD). This limits the utility of LOD as a morphological descriptor and as a predictor of peri- and postoperative outcomes. Consequently, our aim was to establish definitions for LOD via consensus of expert abdominal wall surgeons. METHODS: A Delphi study involving 20 internationally recognized abdominal wall reconstruction (AWR) surgeons was performed. Four written and two volumetric definitions of LOD were identified via systematic review. Panelists completed a questionnaire that suggested these definitions as standardized definitions of LOD. Consensus on a preferred term was pre-defined as achieved when selected by ≥80% of panelists. Terms scoring <20% were removed. RESULTS: Voting commenced August 2018 and was completed in January 2019. Written definition: During Round 1, two definitions were removed and seven new definitions were suggested, leaving nine definitions for consideration. For Round 2, panelists were asked to select all appealing definitions. Thereafter, common concepts were identified during analysis, from which the facilitators advanced a new written definition. This received 100% agreement in Round 3. Volumetric definition: Initially, panelists were evenly split, but consensus for the Sabbagh method was achieved. Panelists could not reach consensus regarding a threshold LOD value that would preclude surgery. CONCLUSIONS: Consensus for written and volumetric definitions of LOD was achieved from 20 internationally recognized AWR surgeons. Adoption of these definitions will help standardize the use of LOD for both clinical and academic activities.

Nomenclature in Abdominal Wall Hernias: Is It Time for Consensus?

Abdominal wall reconstruction is a rapidly evolving area of surgical interest. Due to the increase in prevalence and size of ventral hernias and the high recurrence rates, the academic community has become motivated to find the best reconstruction techniques. Whilst interrogating the abdominal wall reconstruction literature, we discovered an inconsistency in hernia nomenclature that must be addressed. The terms used to describe the anatomical planes of mesh implantation 'inlay', 'sublay' and 'underlay' are misinterpreted throughout. We describe the misinterpretation of these terms and give evidence of where it exists in the literature. We give three critical arguments of why these misinterpretations hinder advances in abdominal wall reconstruction research. The correct definitions of the anatomical planes, and their respective terms, are described and illustrated. Clearly defined nomenclature is required as academic surgeons strive to improve abdominal wall reconstruction outcomes and lower complication rates.

Anatomical Variation of Abdominal Wall Musculature: An Objective Assessment Using Cross-Sectional Imaging.

Purpose: To determine normal anatomical variation of abdominal wall musculature. Methods: A retrospective analysis of CT scans was performed on adults (>18 years) with normal abdominal wall muscles. Two radiologists analysed the images independently. Distances from three fixed points in the midline were measured. The fixed points were; P1, mid-way between xiphoid and umbilicus, P2, at the umbilicus, and P3, mid-way between umbilicus and pubic symphysis. From these three fixed points the following measurements were recorded; midline to lateral innermost border of the abdominal wall musculature, midline to lateral edge of rectus abdominis muscle, and midline to medial edges of all three lateral abdominal wall muscles. To obtain aponeurotic width, rectus abdominis width was subtracted from the distance to medial edge of lateral abdominal wall muscle. Results: Fifty normal CT scan were evaluated from between March 2023 to August 2023. Mean width of external oblique aponeurosis at P1 was 16.2 mm (IQR 9.2 mm to 20.7 mm), at P2 was 23.5 mm (IQR 14 mm to 33 mm), and at P3 no external oblique muscle was visible. Mean width of the internal oblique aponeurosis at P1 was 32.1 mm (IQR 17.5 mm to 45 mm), at P2 was 10.13 (IQR 1 mm to 17.5 mm), and at P3 was 9.2 mm (IQR 3.0 mm to 13.7 mm). Mean width of the transversus abdominis aponeurosis at P1 was -25.1 mm (IQR 37.8 mm to -15.0 mm), at P2 was 29.4 mm (IQR 20 mm to 39.8 mm), and at P3 was 20.3 mm (IQR 12 mm to 29 mm). Conclusion: In this study we describe normal anatomical variation of the abdominal wall muscles. Assessing this variability on the pre-operative CT scans of ventral hernia patients allows for detailed operative planning and decision making.

A Ventral Hernia Management Pathway; A "Getting It Right First Time" approach to Complex Abdominal Wall Reconstruction.

INTRODUCTION: Abdominal wall reconstruction (AWR) is an emerging specialty, involving complex multi-stage operations in patients with high medical and surgical risk. At our hospital, we have developed a growing interest in AWR, with a commitment to improving outcomes through a regular complex hernia MDT. An MDT approach to these patients is increasingly recognized as the path forward in management to optimize patients and improve outcomes. METHODS: We conducted a literature review and combined this with our experiential knowledge of managing these cases to create a pathway for the management of our abdominal wall patients. This was done under the auspices of GIRFT (Getting It Right First Time) as a quality improvement project at our hospital. RESULTS: We describe, in detail, our current AWR pathway, including the checklists and information documents we use with a stepwise evidence and experience-based approach to identifying the multiple factors associated with good outcomes. We explore the current literature and discuss our best practice pathway. CONCLUSION: In this emerging specialty, there is limited guidance on the management of these patients. Our pathway, the "Complex Hernia Bundle," currently provides guidance for our abdominal wall team and may well be one that could be adopted/adapted by other centers where challenging hernia cases are undertaken.

X-Ray Visible Protein Scaffolds by Bulk Iodination.

Protein-based biomaterial use is expanding within medicine, together with the demand to visualize their placement and behavior in vivo. However, current medical imaging techniques struggle to differentiate between protein-based implants and surrounding tissue. Here a fast, simple, and translational solution for tracking transplanted protein-based scaffolds is presented using X-ray CT-facilitating long-term, non-invasive, and high-resolution imaging. X-ray visible scaffolds are engineered by selectively iodinating tyrosine residues under mild conditions using readily available reagents. To illustrate translatability, a clinically approved hernia repair mesh (based on decellularized porcine dermis) is labeled, preserving morphological and mechanical properties. In a mouse model of mesh implantation, implants retain marked X-ray contrast up to 3 months, together with an unchanged degradation rate and inflammatory response. The technique's compatibility is demonstrated with a range of therapeutically relevant protein formats including bovine, porcine, and jellyfish collagen, as well as silk sutures, enabling a wide range of surgical and regenerative medicine uses. This solution tackles the challenge of visualizing implanted protein-based biomaterials, which conventional imaging methods fail to differentiate from endogenous tissue. This will address previously unanswered questions regarding the accuracy of implantation, degradation rate, migration, and structural integrity, thereby accelerating optimization and safe translation of therapeutic biomaterials.

An active electronic bidirectional interface for high resolution interrogation of the spinal cord.

Epidural electrical stimulation (EES) has shown promise as both a clinical therapeutic tool and research aid in the study of nervous system function. However, available clinical paddles are limited to using a small number of contacts due to the burden of wires necessary to connect each contact to the therapeutic device. Here, we introduce for the first time the integration of a hermetic active electronic multiplexer onto the electrode paddle array itself, removing this interconnect limitation. We evaluated the chronic implantation of an active electronic 60-contact paddle (the HD64) on the lumbosacral spinal cord of two sheep. The HD64 was implanted for 13 months and 15 months, with no device-related malfunctions or adverse events. We identified increased selectivity in EES-evoked motor responses using dense stimulating bipoles. Further, we found that dense recording bipoles decreased the spatial correlation between channels during recordings. Finally, spatial electrode encoding enabled a neural network to accurately perform EES parameter inference for unseen stimulation electrodes, reducing training data requirements. A high-density EES paddle, containing active electronics safely integrated into neural interfaces, opens new avenues for the study of nervous system function and new therapies to treat neural injury and dysfunction.

A Review of Functional Restoration From Spinal Cord Stimulation in Patients With Spinal Cord Injury.

Traumatic spinal cord injury often leads to loss of sensory, motor, and autonomic function below the level of injury. Recent advancements in spinal cord electrical stimulation (SCS) for spinal cord injury have provided potential avenues for restoration of neurologic function in affected patients. This review aims to assess the efficacy of spinal cord stimulation, both epidural (eSCS) and transcutaneous (tSCS), on the return of function in individuals with chronic spinal cord injury. The current literature on human clinical eSCS and tSCS for spinal cord injury was reviewed. Seventy-one relevant studies were included for review, specifically examining changes in volitional movement, changes in muscle activity or spasticity, or return of cardiovascular pulmonary, or genitourinary autonomic function. The total participant sample comprised of 327 patients with spinal cord injury, each evaluated using different stimulation protocols, some for sensorimotor function and others for various autonomic functions. One hundred eight of 127 patients saw improvement in sensorimotor function, 51 of 70 patients saw improvement in autonomic genitourinary function, 32 of 32 patients saw improvement in autonomic pulmonary function, and 32 of 36 patients saw improvement in autonomic cardiovascular function. Although this review highlights SCS as a promising therapeutic neuromodulatory technique to improve rehabilitation in patients with SCI, further mechanistic studies and stimulus parameter optimization are necessary before clinical translation.

Development of Fluoride Protective Values for Aquatic Life Using Empirical Bioavailability Models.

The derivation of protective values for aquatic life can be enhanced by the development and use of bioavailability models. Recent advances to metals bioavailability modeling are applicable to other analyte groups and should be widely considered. We conducted a meta-analysis of the available aquatic toxicity literature for fluoride to evaluate the utility of hardness, alkalinity, and chloride as toxicity-modifying factors (TMFs) in empirical bioavailability models of freshwater taxa. The resulting optimal multiple linear regression model predicting acute fluoride toxicity to the invertebrate Hyalella azteca included all three TMFs (observed vs. predicted 50% lethal concentrations, R2 = 0.88) and the optimal model predicting toxicity to the fish Oncorhynchus mykiss included alkalinity and hardness (R2 = 0.37). At >20 mg/L chloride, the preliminary final acute values for fluoride were within 1 order of magnitude and ranged from approximately 18.1 to 56.3 mg/L, depending on water chemistry. Sensitivity of H. azteca to low-chloride conditions increased model uncertainty when chloride was <20 mg/L. Because of limited toxicity data, chronic bioavailability models were not developed, and final chronic values were derived using an acute-to-chronic ratio (ACR) approach. Accounting for TMFs, the geometric mean ACR was 5.4 for fish and invertebrate taxa (n = 6). The present assessment highlights the need to expand bioavailability modeling to include inorganic anions, particularly fluoride, and demonstrates that existing promulgated protective values for fluoride are likely overly conservative. More toxicological studies are recommended to further refine multivariate empirical bioavailability models for inorganic anions. Environ Toxicol Chem 2022;41:396-409. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Fast inference of spinal neuromodulation for motor control using amortized neural networks.

Objective.Epidural electrical stimulation (EES) has emerged as an approach to restore motor function following spinal cord injury (SCI). However, identifying optimal EES parameters presents a significant challenge due to the complex and stochastic nature of muscle control and the combinatorial explosion of possible parameter configurations. Here, we describe a machine-learning approach that leverages modern deep neural networks to learn bidirectional mappings between the space of permissible EES parameters and target motor outputs.Approach.We collected data from four sheep implanted with two 24-contact EES electrode arrays on the lumbosacral spinal cord. Muscle activity was recorded from four bilateral hindlimb electromyography (EMG) sensors. We introduce a general learning framework to identify EES parameters capable of generating desired patterns of EMG activity. Specifically, we first amortize spinal sensorimotor computations in a forward neural network model that learns to predict motor outputs based on EES parameters. Then, we employ a second neural network as an inverse model, which reuses the amortized knowledge learned by the forward model to guide the selection of EES parameters.Main results.We found that neural networks can functionally approximate spinal sensorimotor computations by accurately predicting EMG outputs based on EES parameters. The generalization capability of the forward model critically benefited our inverse model. We successfully identified novel EES parameters, in under 20 min, capable of producing desired target EMG recruitment duringin vivotesting. Furthermore, we discovered potential functional redundancies within the spinal sensorimotor networks by identifying unique EES parameters that result in similar motor outcomes. Together, these results suggest that our framework is well-suited to probe spinal circuitry and control muscle recruitment in a completely data-driven manner.Significance.We successfully identify novel EES parameters within minutes, capable of producing desired EMG recruitment. Our approach is data-driven, subject-agnostic, automated, and orders of magnitude faster than manual approaches.

Concurrent stimulation and sensing in bi-directional brain interfaces: a multi-site translational experience.

Objective. To provide a design analysis and guidance framework for the implementation of concurrent stimulation and sensing during adaptive deep brain stimulation (aDBS) with particular emphasis on artifact mitigations.Approach. We defined a general architecture of feedback-enabled devices, identified key components in the signal chain which might result in unwanted artifacts and proposed methods that might ultimately enable improved aDBS therapies. We gathered data from research subjects chronically-implanted with an investigational aDBS system, Summit RC + S, to characterize and explore artifact mitigations arising from concurrent stimulation and sensing. We then used a prototype investigational implantable device, DyNeuMo, and a bench-setup that accounts for tissue-electrode properties, to confirm our observations and verify mitigations. The strategies to reduce transient stimulation artifacts and improve performance during aDBS were confirmed in a chronic implant using updated configuration settings.Main results.We derived and validated a 'checklist' of configuration settings to improve system performance and areas for future device improvement. Key considerations for the configuration include (a) active instead of passive recharge, (b) sense-channel blanking in the amplifier, (c) high-pass filter settings, (d) tissue-electrode impedance mismatch management, (e) time-frequency trade-offs in the classifier, (f) algorithm blanking and transition rate limits. Without proper channel configuration, the aDBS algorithm was susceptible to limit-cycles of oscillating stimulation independent of physiological state. By applying the checklist, we could optimize each block's performance characteristics within the overall system. With system-level optimization, a 'fast' aDBS prototype algorithm was demonstrated to be feasible without reentrant loops, and with noise performance suitable for subcortical brain circuits.Significance. We present a framework to study sources and propose mitigations of artifacts in devices that provide chronic aDBS. This work highlights the trade-offs in performance as novel sensing devices translate to the clinic. Finding the appropriate balance of constraints is imperative for successful translation of aDBS therapies.Clinical trial:Institutional Review Board and Investigational Device Exemption numbers: NCT02649166/IRB201501021 (University of Florida), NCT04043403/IRB52548 (Stanford University), NCT03582891/IRB1824454 (University of California San Francisco). IDE #180 097.

Intraoperative Monitoring of Spinal Cord Perfusion using Ultrasound in an Ovine Model.

Ultrasound imaging can be used to visualize the spinal cord and assess localized cord perfusion. We present in vivo data in an ovine model undergoing spinal cord stimulation and propose development of transcutaneous US imaging as a potential non-invasive imaging modality in spinal cord injury.Clinical Relevance- Ultrasound imaging can be used to aid in prognosis and diagnosis by providing qualitative and quantitative characterization of the spinal cord. This modality can be developed as a low cost, portable, and non-invasive imaging technique in spinal injury patients.

Penta-fluoro-phenyl (3R,4R,5S)-5-{[(3R,4R,5S)-5-azido-methyl-3,4-dimeth-oxy-2,3,4,5-tetra-hydro-furan-3-carboxamido]-meth-yl}-3,4-dimeth-oxy-2,3,4,5-tetra-hydro-furan-3-carboxyl-ate.

The title compound, C(22)H(25)F(5)N(4)O(9), is a stable penta-fluoro-phenyl ester inter-mediate in the synthesis of novel homo-oligomeric structures containing branched carbon chains. The structure is epimeric to the previously characterized dimeric penta-fluoro-phenyl ester with stereochemistry (3R,4R,5R), which was synthesized using d-ribose as starting material. The crystal structure of the title mol-ecule removes any ambiguities arising from the relative stereochemistries of the six chiral centres. Two hydrogen bonds, bifurcating from the NH group, stabilize the crystal: one intra-molecular and one inter-molecular, both involving O atoms of the meth-oxy groups. The asymmetric unit contains two independent mol-ecules not related by any pseudo-symmetry operators. The major conformational differences are localized, leading to one mol-ecule being extended compared to the other. The collected crystal was twinned (twin ratio is 0.939:0.061), and the azide group is positionally disordered over two positions in one mol-ecule [occupancy ratio 0.511 (18):0.489 (18)].

"It's ok if it's hidden": The discursive construction of everyday racism for refugees and asylum seekers in Wales.

Wales has a long history of migration; however, the introduction of dispersed asylum seekers in 2001 has led to Wales becoming a more superdiverse nation. Wales has often been positioned as a more "tolerant nation" than England; however, the increasingly superdiverse nature of Wales in a postdevolution era may now be calling this tolerance thesis into question. Models of refugee and asylum seeker integration suggest that the absence of racism plays a key role in integration. This paper reports the findings of research that centres on refugee and asylum seeker integration in Wales. Nineteen interviews were conducted with refugees and asylum seekers who had been living in Wales for between 1 month and 12 years. Each interview was analysed using a discursive psychology approach. In this paper, I show that the interviewees appeared to negotiate a dilemma when talking about experiencing potentially racist incidents within the interviews, constructing them as trivial so as not to appear critical of the protection they have received in Wales. The findings also highlight the more everyday and banal forms of racism that are regularly experienced by refugees and asylum seekers living in Wales.

Incisional Hernia in Renal Transplant Recipients: A Systematic Review.

Incisional hernia follows midline laparotomy in 8 to 20 per cent of cases, but the rate following lateral incision is not well documented. This systematic review summarizes incisional hernia rate after open renal transplant. We searched EMBASE, MEDLINE, and the Cochrane Library databases from January 2000 to November 2016 inclusive. The outcomes included in our analysis were the posttransplant incisional hernia rate, significant patient risk factors for incisional hernia, the definition of incisional hernia used, the method used to detect incisional hernia, and the incision used for transplantation. Eight retrospective case series were identified, three describing renal transplant recipients and five describing incisional hernia repairs postrenal transplant. All reported the incisional hernia rate postrenal transplant at the host institution. The hernia rate ranged from 1.1 to 7.0 per cent, with a mean of 3.2 per cent. Factors associated with incisional hernia were body mass index >30, age >50, cadaveric graft, and reoperation through the same incision. Despite the significant comorbidity of renal transplant recipients, the incisional hernia rate postrenal transplant is significantly lower than that of post-midline laparotomy. The reasons for this are discussed. This demonstrates the importance of operative technique, local tissue quality and biomechanical factors in the formation of incisional hernia.

A systematic methodological review of reported perioperative variables, postoperative outcomes and hernia recurrence from randomised controlled trials of elective ventral hernia repair: clear definitions and standardised datasets are needed.

BACKGROUND: This systematic review assesses the perioperative variables and post-operative outcomes reported by randomised controlled trials (RCTs) of VH repair. This review focuses particularly on definitions of hernia recurrence and techniques used for detection. OBJECTIVE: Our aim is to identify and quantify the inconsistencies in perioperative variable and postoperative outcome reporting, so as to justify future development of clear definitions of hernia recurrence and a standardised dataset of such variables. METHODS: The PubMed database was searched for elective VH repair RCTs reported January 1995 to March 2016 inclusive. Three independent reviewers performed article screening, and two reviewers independently extracted data. Hernia recurrence, recurrence rate, timing and definitions of recurrence, and techniques used to detect recurrence were extracted. We also assessed reported post-operative complications, standardised operative outcomes, patient reported outcomes, pre-operative CT scan hernia dimensions, intra-operative variables, patient co-morbidity, and hernia morphology. RESULTS: 31 RCTs (3367 patients) were identified. Only 6 (19.3%) defined hernia recurrence and methods to detect recurrence were inconsistent. Sixty-four different clinical outcomes were reported across the RCTs, with wound infection (30 trials, 96.7%), hernia recurrence (30, 96.7%), seroma (29, 93.5%), length of hospital stay (22, 71%) and haematoma (21, 67.7%) reported most frequently. Fourteen (45%), 11 (35%) and 0 trials reported CT measurements of hernia defect area, width and loss of domain, respectively. No trial graded hernias using generally accepted scales. CONCLUSION: VH RCTs report peri- and post-operative variables inconsistently, and with poor definitions. A standardised minimum dataset, including definitions of recurrence, is required.