The correlation between altmetric score and traditional measures of article impact for studies pertaining to spine trauma.

PURPOSE: It is becoming increasingly common for researchers to share scientific literature via social media. Traditional bibliometrics have long been utilized to measure a study's academic impact, but they fail to capture the impact generated through social media sharing. Altmetric Attention Score (AAS) is a weighted count of all the online attention garnered by a study, and it is currently unclear whether a relationship with traditional bibliometrics exists. METHODS: We identified the five highest-rated spine-specific and five highest-rated general orthopedic journals by Scopus CiteScore 2020. We then identified all the spine trauma studies across a 5-year span (2016-2020) within these journals and compared AAS with traditional bibliometrics using Independent t-tests and Pearson's correlational analyses. RESULTS: No statistically significant relationships were identified between AAS and traditional bibliometrics for articles pertaining to spine trauma: Level of Evidence (R = - 0.02, p = 0.34), H-Index Primary Author (R = < - 0.01, p = 0.50), H-Index Senior Author (R = - 0.04, p = 0.24), and Number of Citations (R = 0.01, p = 0.40). The top five articles by AAS include those pertaining to motorcycle injuries (AAS = 687), orthosis in thoracolumbar fractures (AAS = 199), golfing injuries (AAS = 166), smartphone-based teleradiology (AAS = 41), and auto racing injuries (AAS = 39). CONCLUSION: The lack of overlap between these types of metrics suggests that AAS or similar alternative metrics should be used to measure an article's social impact. The social impact of an article should likewise be a factor in determining an article's overall impact along with its academic impact as measured by bibliometrics.

Biomechanical and ergonomic risks associated with cervical musculoskeletal dysfunction amongst surgeons: A systematic review.

INTRODUCTION: Surgeons are at high risk of developing musculoskeletal symptoms due to a range of factors including, maladaptive positioning and surgical ergonomics. Cervical muscle strain and biomechanical load is most prevalent due to repetitive motions and prolonged static neck positioning. This issue is apparent through reports of prevalence between 10 and 74.4% among surgeons. The aim of this systematic review is to provide an objective assessment of the clinical evidence available and a descriptive analysis of the effects of kinematics and surgical ergonomics on the prevalence of surgeons' cervical musculoskeletal pain. METHODS: This is PRISMA-compliant systematic review of clinical studies assessing the prevalence of cervical musculoskeletal dysfunction in surgeons by searching PUBMED and Ovid EMBASE databases from inception to 19th October 2023. Study quality was graded according to the National Institutes of Health study quality assessment tools. RESULTS: A total of 9 studies were included in the final qualitative analysis. The use of loupes, open surgery and excessive neck flexion (>30°) were associated with cervical dysfunction. Comparison of study outcomes was challenging due to heterogeneity within study methods and the paucity of methodological quality. CONCLUSION: The current literature assessing ergonomic and biomechanical factors predisposing surgeons to cervical musculoskeletal dysfunction is insufficient to provide reliable guidance for clinicians. Although the literature identifies factors contributing to work-related cervical dysfunction, few attempt to evaluate interventions for improved surgical ergonomics. An objective assessment of interventions that prompt postural correction with the aim to improve neck pain in surgeon cohorts is warranted.

Nocturnal swallowing augments arousal intensity and arousal tachycardia.

Cortical arousal from sleep is associated with autonomic activation and acute increases in heart rate. Arousals vary considerably in their frequency, intensity/duration, and physiological effects. Sleep and arousability impact health acutely (daytime cognitive function) and long-term (cardiovascular outcomes). Yet factors that modify the arousal intensity and autonomic activity remain enigmatic. In this study of healthy human adults, we examined whether reflex airway defense mechanisms, specifically swallowing or glottic adduction, influenced cardiac autonomic activity and cortical arousal from sleep. We found, in all subjects, that swallows trigger rapid, robust, and patterned tachycardia conserved across wake, sleep, and arousal states. Tachycardia onset was temporally matched to glottic adduction-the first phase of swallow motor program. Multiple swallows increase the magnitude of tachycardia via temporal summation, and blood pressure increases as a function of the degree of tachycardia. During sleep, swallows were overwhelmingly associated with arousal. Critically, swallows were causally linked to the intense, prolonged cortical arousals and marked tachycardia. Arousal duration and tachycardia increased in parallel as a function of swallow incidence. Our findings suggest that cortical feedback and tachycardia are integrated responses of the swallow motor program. Our work highlights the functional influence of episodic, involuntary airway defense reflexes on sleep and vigilance and cardiovascular function in healthy individuals.

Measurement of the Nucleon F_{2}

The ratio of the nucleon F_{2} structure functions, F_{2}^{n}/F_{2}^{p}, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from ^{3}H and ^{3}He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19

Pragmatic diagnostic and therapeutic algorithms to optimize new potassium binder use in cardiorenal disease.

BACKGROUND: Pivotal randomized trials demonstrating efficacy, safety and good tolerance, of two new potassium binders (patiromer and sodium zirconium cyclosilicate) led to their recent approval. A major hurdle to the implementation of these potassium-binders is understanding how to integrate them safely and effectively into the long-term management of cardiovascular and kidney disease patients using renin angiotensin aldosterone system inhibitors (RAASi), the latter being prone to induce hyperkalaemia. METHODS: A multidisciplinary academic panel including nephrologists and cardiologists was convened to develop consensus therapeutic algorithm(s) aimed at optimizing the use of the two novel potassium binders (patiromer and sodium zirconium cyclosilicate) in stable adults who require treatment with RAASi and experience(d) hyperkalaemia in a non-emergent setting. RESULTS: Two dedicated pragmatic algorithms are proposed. The lowest intervention threshold (i.e. 5.1 mmol/L or greater) was the one used in the patiromer and sodium zirconium cyclosilicate) pivotal trials, both drugs being indicated to treat hyperkalaemia in a non -emergent setting. Acknowledging the heterogeneity across specialty guidelines in hyperkalaemia definition and thresholds to intervene when facing hyperkalaemia, we have been mindful to use soft language i.e. "it is to consider", not necessarily "to do". CONCLUSIONS: Providing the clinical community with pragmatic algorithms may help optimize the management of high-risk patients by avoiding the risks of both hyper and hypokalaemia and of suboptimal RAASi therapy.

Tracking the progress of inflammation with PET/MRI in a canine model of myocardial infarction.

BACKGROUND: Following myocardial infarction, tissue undergoes pathophysiological changes involving inflammation and scar tissue formation. However, little is known about the pathophysiology and prognostic significance of any corresponding changes in remote myocardium. The aim of this study was to investigate the potential application of a combined constant infusion of 18F-FDG and Gd-DTPA to quantitate inflammation and extracellular volume (ECV) from 3 to 40 days after myocardial infarction. METHODS: Eight canine subjects were imaged at multiple time points following induction of an MI with a 60-minute concurrent constant infusion of Gd-DTPA and 18F-FDG using a hybrid PET/MRI scanner. RESULTS: There was a significant increase in ECV in remote myocardium on day 14 post-MI (P = .034) and day 21 (P = .021) compared to the baseline. ECV was significantly elevated in the infarcted myocardium compared to remote myocardium at all time points post-MI (days 3, 7, 14, 21, and 40) (P < .001) while glucose uptake was also increased within the infarct on days 3, 7, 14, and 21 but not 40. CONCLUSIONS: The significant increase in ECV in remote tissue may be due to an ongoing inflammatory process in the early weeks post-infarct.

Simultaneous measurements of myocardial glucose metabolism and extracellular volumes with hybrid PET/MRI using concurrent injections of Gd-DTPA and [18F]FDG.

BACKGROUND: The aims of this study were to investigate the application of a constant infusion (CI) to mitigate the issue of constantly changing Gd-DTPA contrast levels in a bolus injection for extracellular volume (ECV) measurements by (a) comparing a CI alone to a bolus alone and a bolus followed by CI in healthy myocardium, (b) evaluating the impact of glucose suppression using heparin on ECV. METHODS: Five healthy canine subjects were imaged to compare three different protocols for injecting Gd-DTPA and FDG: bolus alone, CI alone, bolus followed by CI. Suppression of myocardial glucose uptake was induced using a continuous infusion of 20% lipid at a rate of 0.25 mL·min-1·kg-1 as well as 2000 units of intravenous heparin injected 20 minutes prior to FDG/Gd-DTPA injection. RESULTS: There was no significant effect on ECV measurement when heparin was used for glucose suppression at equilibrium irrespective of infusion protocol). Measurements of ECV in myocardium, regardless of infusion protocol showed no significant difference at all time points (P = 0.21) prior to washout. CONCLUSIONS: The suppression of myocardial uptake of [18F]FDG with heparin did not alter the determination of myocardial ECV though a larger sample size may show differences. Further, the infusion protocol (bolus or constant infusion) had no effect on the calculated ECV.

The efficacy of remote virtual care in comparison to traditional clinical visits for elective orthopaedic patients: A meta-analysis of prospective randomised controlled trials.

INTRODUCTION: The Orthopaedic Trauma Association has recommended limitation of in-person encounters to absolute necessity. One method of ensuring standard patient care within these guidelines is through the implementation of telemedicine. AIMS: To evaluate the efficacy of telemedicine for elective orthopaedic patients in the recovery and/or rehabilitation period. METHODS: A systematic review and meta-analysis of articles in Medline/PubMed and The Cochrane Library databases was performed according to the PRISMA guidelines for prospective randomised controlled trials to compare clinical and symptomatic measures for elective patients managed routinely with remote care compared to those managed with standard in-clinic management. To be included for meta-analysis, parameters must be evaluated in ≥3 studies. RESULTS: Eleven studies were included in the meta-analyses. Both telemedicine and control cohorts were comparable for patient satisfaction (RR, 0.98; 95% CI, 0.90-1.07; I2 = 0%; p = 0.52) and patient retention analysis (RR, 1.25; 95% CI, 0.51-3.06; p = 0.54; I2 = 0%). Similarly, there was no statistical difference appreciated between cohorts for overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (p = 0.30), Timed Up and Go Test (p = 0.40), and Stair Test (p = 0.18). Significant difference did exist for visual analogue scale (VAS) scores (p = 0.02) in favour of in-clinic management. CONCLUSION: Telemedicine will serve an integral aspect of healthcare delivery throughout the current COVID-19 pandemic and beyond in an effort to deliver safe, efficient and time-sensitive care to the orthopaedic patient population. The results of our meta-analyses indicate that virtual consultations are as effective as traditional in-person consultations for the care of elective orthopaedic patients in the recovery and rehabilitation period. However, further studies are needed to evaluate for initial consultations and certain sub-specialties of orthopaedics.

Altered inflammasome activation in neonatal encephalopathy persists in childhood.

Neonatal encephalopathy (NE) is characterized by altered neurological function in term infants and inflammation plays an important pathophysiological role. Inflammatory cytokines interleukin (IL)-1ß, IL-1ra and IL-18 are activated by the nucleotide-binding and oligomerization domain (NOD)-, leucine-rich repeat domain (LRR)- and NOD-like receptor protein 3 (NLRP3) inflammasome; furthermore, we aimed to examine the role of the inflammasome multiprotein complex involved in proinflammatory responses from the newborn period to childhood in NE. Cytokine concentrations were measured by multiplex enzyme-linked immunosorbent assay (ELISA) in neonates and children with NE in the absence or presence of lipopolysaccharide (LPS) endotoxin. We then investigated expression of the NLRP3 inflammasome genes, NLRP3, IL-1ß and ASC by polymerase chain reaction (PCR). Serum samples from 40 NE patients at days 1 and 3 of the first week of life and in 37 patients at age 4-7 years were analysed. An increase in serum IL-1ra and IL-18 in neonates with NE on days 1 and 3 was observed compared to neonatal controls. IL-1ra in NE was decreased to normal levels at school age, whereas serum IL-18 in NE was even higher at school age compared to school age controls and NE in the first week of life. Percentage of LPS response was higher in newborns compared to school-age NE. NLRP3 and IL-1ß gene expression were up-regulated in the presence of LPS in NE neonates and NLRP3 gene expression remained up-regulated at school age in NE patients compared to controls. Increased inflammasome activation in the first day of life in NE persists in childhood, and may increase the window for therapeutic intervention.

Systems biology predicts that fibrosis in tuberculous granulomas may arise through macrophage-to-myofibroblast transformation.

Mycobacterium tuberculosis (Mtb) infection causes tuberculosis (TB), a disease characterized by development of granulomas. Granulomas consist of activated immune cells that cluster together to limit bacterial growth and restrict dissemination. Control of the TB epidemic has been limited by lengthy drug regimens, antibiotic resistance, and lack of a robustly efficacious vaccine. Fibrosis commonly occurs during treatment and is associated with both positive and negative disease outcomes in TB but little is known about the processes that initiate fibrosis in granulomas. Human and nonhuman primate granulomas undergoing fibrosis can have spindle-shaped macrophages with fibroblast-like morphologies suggesting a relationship between macrophages, fibroblasts, and granuloma fibrosis. This relationship has been difficult to investigate because of the limited availability of human pathology samples, the time scale involved in human TB, and overlap between fibroblast and myeloid cell markers in tissues. To better understand the origins of fibrosis in TB, we used a computational model of TB granuloma biology to identify factors that drive fibrosis over the course of local disease progression. We validated the model with granulomas from nonhuman primates to delineate myeloid cells and lung-resident fibroblasts. Our results suggest that peripheral granuloma fibrosis, which is commonly observed, can arise through macrophage-to-myofibroblast transformation (MMT). Further, we hypothesize that MMT is induced in M1 macrophages through a sequential combination of inflammatory and anti-inflammatory signaling in granuloma macrophages. We predict that MMT may be a mechanism underlying granuloma-associated fibrosis and warrants further investigation into myeloid cells as drivers of fibrotic disease.

The impact of medical and recreational marijuana laws on opioid prescribing in employer-sponsored health insurance.

Using data from Truven Health MarketScan Commercial Claims and Encounters Database between 2009 and 2015, we studied the effects of medical and recreational marijuana laws on opioid prescribing in employer-sponsored health insurance. We used a differences-in-differences (DD) approach and found that the implementation of medical marijuana laws (MMLs) and recreational marijuana laws (RMLs) reduced morphine milligram equivalents per enrollee by 7% and 13%, respectively. The reduction associated with MMLs was predominately in people aged 55-64, whereas the reduction associated with RMLs was largely in people aged 35-44 and aged 45-54. Our findings suggest that both MMLs and RMLs have the potential to reduce opioid prescribing in the privately insured population, especially for the middle-aged population.

A traditional Ugandan Ficus natalensis bark cloth exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus.

AIMS: Surgical site, soft tissue and wound infections are some of the most prominent causes of healthcare-associated infections (HCAIs). Developing novel antimicrobial textiles and wound dressings may help alleviate the risk of developing HCAIs. We aimed to determine the antimicrobial efficacy of natural Ugandan bark cloth derived exclusively from the Ficus natalensis tree. METHODS AND RESULTS: Antimicrobial contact and disc diffusion assays, coupled with time-kill kinetic assays, demonstrated that bark cloth inhibited the growth of a clinically relevant methicillin-resistant Staphylococcus aureus (MRSA) strain and acted as a bactericidal agent causing a seven-log reduction in bacterial viability. Scanning electron microscopy was used to reveal morphological changes in the bacterial cell ultrastructure when exposed to bark cloth, which supported a proposed mechanism of antimicrobial activity. CONCLUSIONS: The observed antimicrobial properties, combined with the physical characteristics elicited by bark cloth, suggest this product is ideally suited for wound and other skin care applications. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report where a whole bark cloth product made by traditional methods has been employed as an antimicrobial fabric against MRSA. Bark cloth is a highly sustainable and renewable product and this study presents a major advance in the search for natural fabrics which could be deployed for healthcare applications.

A randomised trial of bilateral erector spinae plane block vs. no block for thoracolumbar decompressive spinal surgery.

Major spinal surgery causes significant postoperative pain. We tested the efficacy and safety of bilateral erector spinae block on quality of recovery and pain after thoracolumbar decompression. We randomly allocated 60 adults to standard care or erector spinae block. Erector spinae block improved the mean (SD) quality of recovery-15 score at 24 postoperative hours, from 119 (20) to 132 (14), an increase (95%CI) of 13 (4-22), p = 0.0044. Median (IQR [range]) comprehensive complication index was 1 (0-3 [0-5]) in the control group vs. 1 (0-1 [0-4]) after block, p = 0.4. Erector spinae block reduced mean (SD) area under the curve pain during the first 24 postoperative hours: at rest, from 78 (49) to 50 (39), p = 0.018; and on sitting, from 125 (51) to 91 (50), p = 0.009. The cumulative mean (SD) oxycodone consumption to 24 h was 27 (18) mg in the control group and 19 (26) mg after block, p = 0.20. In conclusion, erector spinae block improved recovery and reduced pain for 24 h after thoracolumbar decompression surgery.

Exploring Staff Implementation of a Self-directed Parenting Intervention for Parents with Mental Health Difficulties.

Parents with mental health difficulties face significant barriers in accessing evidence-based parenting interventions. Self-directed approaches may be a destigmatising, accessible alternative. Evidence has suggested that Triple P Positive Parenting Programme's self-directed format is as effective as more time- and cost-intensive delivery methods. The aim of the current study was to establish whether staff were able to use this intervention with parents with mental health difficulties and to explore staff experiences of implementation. Triple P self-help workbooks were provided to practitioners across three teams. Data were collected regarding workbook uptake and use. Interviews with staff exploring their experiences of implementation were analysed using thematic analysis. Overall, 41 participants were recruited, of which 12 (29.27%) also consented to interviews. Overall, six practitioners (14.63%) reported that they utilised the workbook. Uptake and utilisation were varied, but practitioners who used the workbook reported positive outcomes. Interviews revealed themes regarding practitioner concerns, views of the intervention and implementation issues. Self-directed Triple remains a promising intervention but its feasibility is dependent on addressing barriers to implementation and facilitating a family-focused approach to meet the needs of these parents and their children.

Same day comparison of PET/CT and PET/MR in patients with cardiac sarcoidosis.

BACKGROUND: Inflammatory cardiac disorders, in particular, sarcoidosis, play an important role in left ventricular dysfunction, conduction abnormalities, and arrhythmias. In this study, we compared the imaging characteristics and diagnostic information obtained when patients were imaged sequentially with PET/CT and then with hybrid PET/MRI on the same day following a single 18F-FDG injection. METHODS: Ten patients with known or suspected sarcoidosis underwent imaging in sequence of (a) 99mTc-MIBI, (b) 18F-FDG with PET/CT, and (c) 18F-FDG with 3T PET/MRI. Images were compared quantitatively by determination of SUVmax and SUV on a voxel by voxel basis, and qualitatively by two experienced observers. RESULTS: When both platforms were compared quantitatively, similar data for the evaluation of enhanced 18F-FDG uptake were obtained. Qualitatively, there were (1) several instances of normal perfusion with delayed enhancement and/or focal 18F-FDG uptake, (2) comparable enhanced 18F-FDG uptake on PET/CT vs. PET/MRI, and (3) diversity in disease patterns with delayed enhancement only, increased 18F-FDG uptake only, or both. CONCLUSION: In this limited patient study, PET/CT and PET/MR provided similar diagnostic data for 18F-FDG uptake, and the concurrent acquisition of MR images provided further insight into the disease process.

Trends in Mental Health Presentations to a Paediatric Emergency Department.

Aims This study aimed to analyse trends in mental health presentations to the Emergency Department (ED), which anecdotally had increased over the past decade. Methods The ED's electronic 'Symphony' system was used to identify the annual number of presentations categorised as having a mental health complaint from 2006-2017. A detailed analysis was performed on presentations over a one-year period. Results The number of presentations increased from 69 in 2006 to a peak of 432 in 2016 (526% increase). The overall admission rate was 33.3%(n=99), while 52.5%(n=156) of presentations occurred outside of standard working hours. Similar increases were documented by other ED's worldwide, and the WHO estimate that neuropsychiatric disorders will become one of the top five causes of morbidity, mortality and disability among children by 2020. Conclusion With the number of mental health presentations dramatically increasing, carefully designed and integrated strategies are required to pro-actively tackle this growing epidemic.

Auto-Decompression - Preserved Neurological Function in Bilateral Cervical Facet Dislocations

Introduction Bilateral cervical facet dislocation (BCFD) is an uncommon injury with a high incidence of severe neurological impairment. We describe 4 cases of BCFD with preserved neurological function. Cases Case 1: A 78-year-old female who suffered two ground level falls (GLFs). Pre-operative American Spinal Injury Association (ASIA) Score was C5D. Imaging revealed a BCFD at C6/C7 and a C6 laminar fracture. Case 2: A 63-year-old male suffered a fall down 14 steps. Pre-operative ASIA score was E. Imaging demonstrated a BCFD at C7/T1, and a C6 laminar fracture. Case 3: A 46-year-old male collided with a tree while descending a hill on a bicycle. Pre-operative ASIA score was C6D. Imaging revealed a BCFD at C7/T1 and a C7 laminar fracture. Case 4: A 67-year-old male suffered a GLF while exiting a stationary car. Pre-operative ASIA score on admission was E. Imaging revealed a BCFD at C6/C7 with bilateral laminar fractures at C5 and C6. Outcome All cases underwent 2-stage surgical fixation. All cases maintained or had an improved ASIA score post-operatively. Conclusion In all cases, the presence of concurrent laminar fractures resulted in an auto-decompression of the spinal canal, preserving neurological function.

Discharge properties of human diaphragm motor units with ageing.

KEY POINTS: Ageing is associated with changes in the respiratory system including in the lungs, rib cage and muscles. Neural drive to the diaphragm, the principal inspiratory muscle, has been reported to increase during quiet breathing with ageing. We demonstrated that low-threshold motor units of the human diaphragm recruited during quiet breathing have similar discharge frequencies across age groups and shorter discharge times in older age. With ageing, motor unit action potential area increased. We propose that there are minimal functionally significant changes in the discharge properties of diaphragm motor units with ageing despite remodelling of the motor unit in the periphery. ABSTRACT: There are changes in the skeletal, pulmonary and respiratory neuromuscular systems with healthy ageing. During eupnoea, one study has shown relatively higher crural diaphragm electromyographic activity (EMG) in healthy older adults (>51 years) than in younger adults, but these measures may be affected by the normalisation process used. A more direct method to assess neural drive involves the measurement of discharge properties of motor units. Here, to assess age-related changes in neural drive to the diaphragm during eupnoea, EMG was recorded from the costal diaphragm using a monopolar needle electrode in participants from three age groups (n ≥ 7 each): older (65-80 years); middle-aged (43-55 years) and young (23-26 years). In each group, 154, 174 and 110 single motor units were discriminated, respectively. A mixed-effects linear model showed no significant differences between age groups for onset (group mean range 9.5-10.2 Hz), peak (14.1-15.0 Hz) or offset (7.8-8.5 Hz) discharge frequencies during eupnoea. The motor unit recruitment was delayed in the older group (by ∼15% of inspiratory time; p = 0.02 cf. middle-aged group) and had an earlier offset time (by ∼15% of inspiratory time; p = 0.04 cf. young group). However, the onset of multiunit activity was similar across groups, consistent with no global increase in neural drive to the diaphragm with ageing. The area of diaphragm motor unit potentials was ∼40% larger in the middle-aged and older groups (P < 0.02), which indicates axonal sprouting and re-innervation of muscle fibres associated with ageing, even in middle-aged participants.

Central sensitization increases the pupil dilation elicited by mechanical pinprick stimulation.

High-frequency electrical stimulation (HFS) of skin nociceptors triggers central sensitization (CS), manifested as increased pinprick sensitivity of the skin surrounding the site of HFS. Our aim was to assess the effect of CS on pinprick-evoked pupil dilation responses (PDRs) and pinprick-evoked brain potentials (PEPs). We hypothesized that the increase in the positive wave of PEPs following HFS would result from an enhanced pinprick-evoked phasic response of the locus coeruleus-noradrenergic system (LC-NS), indicated by enhanced PDRs. In 14 healthy volunteers, 64- and 96-mN pinprick stimuli were delivered to the left and right forearms, before and 20 minutes after HFS was applied to one of the two forearms. Both PEPs and pinprick-evoked PDRs were recorded. After HFS, pinprick stimuli were perceived as more intense at the HFS-treated arm compared with baseline and control site, and this increase was similar for both stimulation intensities. Importantly, the pinprick-evoked PDR was also increased, and the increase was stronger for 64- compared with 96-mN stimulation. This is in line with our previous results showing a stronger increase of the PEP positivity at 64 vs. 96-mN stimulation and suggests that the increase in PEP positivity observed in previous studies could relate, at least in part, to enhanced LC-NS activity. However, there was no increase of the PEP positivity in the present study, indicating that enhanced LC-NS activity is not the only determinant of the HFS-induced enhancement of PEPs. Altogether, our results indicate that PDRs are more sensitive for detecting CS than PEPs. NEW & NOTEWORTHY We provide the first demonstration in humans that activity-dependent central sensitization increases pinprick-evoked autonomic arousal measured by enhanced pupil dilation response.

Treatment of heart failure with sodium glucose co-transporter-2 inhibitors in people with type 2 diabetes mellitus: current evidence and future directions.

Diabetes is one the most common comorbidities among people with established heart failure. Interest in heart failure as an outcome among people with diabetes has emerged since it was shown that there was an association between increased risk of hospitalization for heart failure with use of thiazolidinediones and some dipeptidyl peptidase-4 inhibitors. Recently, sodium-glucose co-transporter-2 inhibitors were shown to lead to a reduction in the risk of cardiovascular death and hospitalization for heart failure in people with Type 2 diabetes mellitus and either cardiovascular risk factors or atherosclerotic cardiovascular disease. These findings appear to be consistent in people both with and without a baseline history of heart failure. Based on current evidence there are several clinical scenarios in which the use of sodium-glucose co-transporter-2 inhibitors would be justified for people with heart failure and atherosclerotic cardiovascular disease: (1) in people with a new diagnosis of Type 2 diabetes and for whom anti-hyperglycaemic management strategies are being considered; (2) in people with sub-optimal glycaemic control, regardless of baseline antihyperglycaemic therapy; and (3) in people with symptomatic heart failure (or other high-risk features such as recent hospitalization for heart failure), if glycaemic control is optimized and the individual is on a sulfonylurea or dipeptidyl peptidase-4 inhibitor; here, it may be reasonable to consider substituting one of those therapies for a sodium-glucose co-transporter-2 inhibitor. There are now a number of ongoing trials evaluating the role of sodium-glucose co-transporter-2 inhibitors as therapy for people with established heart failure (with preserved or with reduced ejection fraction) and regardless of the presence of diabetes. These trials will provide the evidence for the safety and efficacy of sodium-glucose co-transporter-2 inhibitors among people with established heart failure.