BACKGROUND: Systemic lupus erythematosus is a chronic, multisystem, inflammatory disease of autoimmune etiology occurring predominantly in women. A major hurdle to the diagnosis, treatment, and therapeutic advancement of this disease is its heterogeneous nature, which presents as a wide range of symptoms such as fatigue, fever, musculoskeletal involvement, neuropsychiatric disorders, and cardiovascular involvement with varying severity. The current therapeutic approach to this disease includes the administration of immunomodulatory drugs that may produce unfavorable secondary effects.
OBJECTIVE: This study explores the known relationship between the autonomic nervous system and inflammatory pathways to improve patient outcomes by treating autonomic nervous system dysregulation in patients via noninvasive vagus nerve stimulation. In this study, data including biomarkers, physiological signals, patient outcomes, and patient quality of life are being collected and analyzed. After completion of the clinical trial, a computer model will be developed to identify the biomarkers and physiological signals related to lupus activity in order to understand how they change with different noninvasive vagus nerve stimulation frequency parameters. Finally, we propose building a decision support system with integrated noninvasive wearable technologies for continuous cardiovascular and peripheral physiological sensing for adaptive, patient-specific optimization of the noninvasive vagus nerve stimulation frequency parameters in real time.
METHODS: The protocol was designed to evaluate the efficacy and safety of transauricular vagus nerve stimulation in patients with systemic lupus erythematosus. This multicenter, national, randomized, double-blind, parallel-group, placebo-controlled study will recruit a minimum of 18 patients diagnosed with this disease. Evaluation and treatment of patients will be conducted in an outpatient clinic and will include 12 visits. Visit 1 consists of a screening session. Subsequent visits up to visit 6 involve mixing treatment and evaluation sessions. Finally, the remaining visits correspond with early and late posttreatment follow-ups.
RESULTS: On November 2022, data collection was initiated. Of the 10 participants scheduled for their initial appointment, 8 met the inclusion criteria, and 6 successfully completed the entire protocol. Patient enrollment and data collection are currently underway and are expected to be completed in December 2023.
CONCLUSIONS: The results of this study will advance patient-tailored vagus nerve stimulation therapies, providing an adjunctive treatment solution for systemic lupus erythematosus that will foster adoption of technology and, thus, expand the population with systemic lupus erythematosus who can benefit from improved autonomic dysregulation, translating into reduced costs and better quality of life.
BACKGROUND: ClinicalTrials.gov NCT05704153; https://clinicaltrials.gov/study/NCT05704153.
UNASSIGNED: DERR1-10.2196/48387.

OBJECTIVE: The global prevalence of overactive bladder (OAB) is estimated at 11.8%. Despite existing treatment options such as sacral neuromodulation, a substantial number of patients remain untreated. One potential alternative is noninvasive transcutaneous electrical stimulation. This form of stimulation does not necessitate the implantation of an electrode, thereby eliminating the need for highly skilled surgeons, expensive implantable devices, or regular hospital visits. We hypothesized that alternative neural pathways can impact bladder contraction.
METHODS: In this pilot study, we conducted transcutaneous electrical stimulation of the abdominal wall (T6-L1), the ear (vagus nerve), and the ankle (tibial nerve) of 3 anesthetized female Sprague-Dawley rats. Stimulation was administered within a range of 20 Hz to 20 kHz, and its impact on intravesical pressure was measured. We focused on 3 primary outcomes related to intravesical pressure: (1) the pressure change from the onset of a contraction to its peak, (2) the average duration of contraction, and (3) the number of contractions within a specified timeframe. These measurements were taken while the bladder was filled with either saline or acetic acid (serving as a model for OAB).
RESULTS: Transcutaneous stimulation of the abdominal wall, ear, and ankle at a frequency of 20 Hz decreased the number of bladder contractions during infusion with acetic acid. As revealed by a comparison of various stimulation frequencies of the tibial nerve during bladder infusion with acetic acid, the duration of contraction was significantly shorter during stimulation at 1 kHz and 3 kHz relative to stimulation at 20 Hz (P = 0.025 and P = 0.044, respectively).
CONCLUSIONS: The application of transcutaneous electrical stimulation to the abdominal wall, ear, and tibial nerve could provide less invasive and more cost-effective treatment options for OAB relative to percutaneous tibial nerve stimulation and sacral neuromodulation. A follow-up study involving a larger sample size is recommended.

The Objective of the present study was to evaluate paravertebral brachial plexus block in sheep. A group of 13 healthy sheep with 20.10 ± 2.20 kg weight and five months of age were used. In phase I, in five sheep, an insulated needle attached to a nerve stimulator was directed to the location of C6, C7, C8 and T1 nerves and a 1.50 mL of a solution containing 1:1 methylene blue 1.00% and lidocaine 1.00% was injected at each site. Then, the cervical and thoracic areas were dissected and assessed in the cadavers. In phase II, cervical paravertebral block with 2.00% lidocaine and subsequent assessments were done in eight live sheep. Cadaveric evaluations revealed dye spread in C6 to T1 nerves: 61.75 ± 5.50, 72.75 ± 9.18, 40.75 ± 2.99 and 18.75 ± 3.30 mm, respectively. In three sheep, dye distribution in the anterior mediastinum was observed. In phase II, the onsets of anesthesia were determined within 10 and 15 min for sensory and motor blocks, respectively. Anesthesia at axillary, musculocutaneous, radial and ulnar skin sites and motor block lasted for 67.50 ± 15.80, 63.70 ± 16.00, 55.00 ± 21.70, 56.70 ± 19.70 and 76.40 ± 24.30 min, respectively. In three sheep, no anesthesia was observed for radial and ulnar skin sites. In conclusion, paravertebral brachial plexus block in sheep provided an acceptable block for the upper parts of the elbow joint, however, it was not effective and reliable for more distal structures.

UNASSIGNED: To evaluate changes in cortical thickness and right posterior insula (r-pIns) gamma-aminobutyric acid (GABA) concentrations in veterans with fibromyalgia treated with auricular percutaneous electric nerve field stimulation (PENFS).
UNASSIGNED: This was a randomized, controlled, open label investigation conducted in a government hospital. Twenty-one veterans with fibromyalgia were randomized to receive either standard therapy (ST; i.e., 4 weekly visits with a pain practitioner) or ST with auricular PENFS (ST + PENFS). Neuroimaging data was collected at baseline (i.e. before the first treatment session) and again within 2 weeks post-treatment.​ Clinical pain and physical function were also assessed at these timepoints. Single-voxel magnetic resonance spectroscopy was carried out in r-pIns to assess changes in r-pIns GABA concentrations and high-resolution T1-weighted images were collected to assess changes in regional gray matter volume using cortical thickness.
UNASSIGNED: Both the ST + PENFS and ST groups reported a decrease in pain with treatment. Volumetric: Cortical thickness significantly decreased in the left middle posterior cingulate (p = 0.018) and increased in the left cuneus (p = 0.014) following ST + PENFS treatment. These findings were significant following FDR correction for multiple comparisons. ST group right hemisphere insula cortical thickness increased post-treatment and was significantly (p = 0.02) inversely correlated with pain scores. ST + PENFS group right hemisphere posterior dorsal cingulate size significantly (p = 0.044) positively correlated with pain scores. GABA: There were no significant correlations with GABA, though a trend was noted towards increased GABA following treatment in both groups (p = 0.083) using a linear mixed effects model.
UNASSIGNED: Results suggest a novel effect of PENFS reflected by differential volumetric changes compared to ST. The changes in GABA that occur in both groups are more likely related to ST. Insular GABA and cortical thickness in key regions of interest may be developed as potential biomarkers for evaluating chronic pain pathology and treatment outcomes.

Patients with lower limb fracture often have acute pain and discomfort from changes in position, and such pain affects early postoperative recovery. This study aimed to compare the applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block (LSPB) in the supine versus lateral position during lower limb fracture surgery.
We included 126 patients who underwent elective internal fixation for lower limb fracture who were divided into the S group and the L group by the random number table method and underwent LSPB guided by ultrasound combined with a nerve stimulator in the supine and lateral positions, respectively. The primary outcome was the dose of sufentanil used in surgery. The secondary outcomes were the maximum VAS (visual analogue scale) pain score at position placing for LSPB, the time of position placing, the time for nerve block,the number of puncture attempts,the haemodynamic indicators, the VAS score at 1, 12, and 24 h following surgery, postoperative satisfactory degree to analgesia and adverse events related to nerve block.
There was no statistically significant difference in dose of sufentanil used between the two groups(P = 0.142). The maximum VAS pain score at position placing(P < 0.01), the time of position placement(P < 0.01), the time for lumbar plexus block and the time of puncture attempts were significantly lower in the S group than in the L group (P < 0.01). However, the time for sacral plexus block was higher in the S group than in the L group (P = 0.029). There was no significant difference in haemodynamic indicators,number of puncture attempts for the sacral plexus, postoperative VAS scores, postoperative satisfactory degree to analgesia or adverse events related to nerve block between the two groups (all P > 0.05).
Our study provides a more comfortable and better accepted anaesthetic regimen for patients undergoing lower limb fracture surgery. LSPB in the supine position is simple to apply and has definite anaesthetic effects. Additionally, it has a high level of postoperative analgesia and therefore should be widely applied.
The trial was registered prior to patient enrolment at the Chinese Clinical Trail Registry (Date:11/03/2021 Number: ChiCTR2100044117 ).

暂无摘要。

BACKGROUND: Repetitive peripheral nerve sensory stimulation (RPSS) is a potential add-on intervention to motor training for rehabilitation of upper limb paresis after stroke. Benefits of RPSS were reported in subjects in the chronic phase after stroke, but there is limited information about the effects of this intervention within the 1st weeks or months. The primary goal of this study is to compare, in a head-to-head proof-of-principle study, the impact of a single session of suprasensory vs. subsensory RPSS on the upper limb motor performance and learning in subjects at different phases after stroke subacute and chronic phases and mild upper limb motor impairments after stroke. In addition, we examine the effects of RPSS on brain perfusion, functional imaging activation, and γ-aminobutyric acid (GABA) levels. Subjects with mild upper limb motor impairments will be tested with MRI and clinical assessment either at an early (7 days to 3 months post-stroke) or at a chronic (>6 months) stage after stroke.
METHODS: In this multicenter, randomized, parallel-group, proof-of-principle clinical trial with blinded assessment of outcomes, we compare the effects of one session of suprasensory or subsensory RPSS in patients with ischemic or hemorrhagic stroke and upper limb paresis. Clinical assessment and MRI will be performed only once in each subject (either at an early or at a chronic stage). The primary outcome is the change in performance in the Jebsen-Taylor test. Secondary outcomes: hand strength, cerebral blood flow assessed with arterial spin labeling, changes in the blood oxygenation level-dependent (BOLD) effect in ipsilesional and contralesional primary motor cortex (M1) on the left and the right hemispheres assessed with functional MRI (fMRI) during a finger-tapping task performed with the paretic hand, and changes in GABA levels in ipsilesional and contralesional M1 evaluated with spectroscopy. The changes in outcomes will be compared in four groups: suprasensory, early; subsensory, early; suprasensory, chronic; and subsensory, chronic.
CONCLUSIONS: The results of this study are relevant to inform future clinical trials to tailor RPSS to patients more likely to benefit from this intervention.
BACKGROUND: NCT03956407.

This paper presents data from a transcutaneous vagus nerve stimulation experiment that point towards a blunted cardiac baroreceptor sensitivity (cBRS) in young males compared to females during electrical stimulation of the forearm and a rhythmic breathing task. Continuous electrocardiography, impedance cardiography and continuous blood-pressure recordings were assessed in a sex-matched cohort of twenty young healthy subjects. Electrical stimulation of the median nerve was conducted by using a threshold-tracking method combined with two rhythmic breathing tasks (0.1 and 0.2 Hz) before, during and after active or sham transcutaneous vagus nerve stimulation. Autonomic and hemodynamic parameters were calculated, and differences were analyzed by using linear mixed models and post hoc F-tests. None of the autonomic and hemodynamic parameters differed between the sham and active conditions. However, compared to females, male participants had an overall lower total cBRS independent of stimulation condition during nerve stimulation (females: 14.96 ± 5.67 ms/mmHg, males: 11.89 ± 3.24 ms/mmHg, p = 0.031) and rhythmic breathing at 0.2 Hz (females: 21.49 ± 8.47 ms/mmHg, males: 15.12 ± 5.70 ms/mmHg, p = 0.004). Whereas vagus nerve stimulation at the left inner tragus did not affect the efferent vagal control of the heart, we found similar patterns of baroreceptor sensitivity activation over the stimulation period in both sexes, which, however, significantly differed in their magnitude, with females showing an overall higher cBRS.

OBJECTIVE: Ultrasound guidance does not eliminate the risk of intraneural injection, which must be avoided during PNB. Combining ultrasound guidance (USG), nerve stimulation (NS), and injection pressure monitoring is advocated to prevent nerve injury during PNB. We hypothesized that combining patient-tailored dynamic NS and real-time pressure sensing (RTPS) could reduce the incidence of intraneural injection and nerve puncture during USG PNB compared with a traditional fixed thresholds (Control) procedure.
METHODS: Randomized, prospective study.
METHODS: Operating room.
METHODS: One hundred ASA physical status I to III patients undergoing orthopedic surgery.
METHODS: Patient anesthetized using axillary, sciatic or femoral USG PNB were randomized to the PresStim group (Dynamic RTPS and NS set at 1.5 mA then decreased; n = 50) or Control group (fixed thresholds for in-line pressure mechanical manometer and NS at 0.2 mA; n = 50).
METHODS: Procedural ultrasound images and videos were recorded, stored and reviewed in random order by two experts in ultrasound-guided PNB blinded to the group. They noted the needle-to-nerve relationship and intraneural injection for all blocked nerves.
RESULTS: One hundred and twenty-three USG PNBs were performed (56 axillary brachial plexus blocks, 40 femoral nerve blocks and 27 sciatic popliteal nerve blocks); 235 blocked nerves and videos were recorded and analyzed (PresStim, 118; Control, 117). Less paresthesia was noted in the PresStim group (12.7%) compared with the Control group (18.8%). The risk of intraneural injection was significantly higher in the Control group (odds ratio [OR], 17.1; 95% confidence interval [CI], 2.2-135, P = 0.007). The risk of nerve puncture (OR, 22.7; 95% CI, 2.9-175, p = 0.003) and needle-nerve contact (OR, 4.7; 95% CI, 2.4-9.5, p < 0.001) was significantly higher in the Control group than the PresStim group.
CONCLUSIONS: Under the conditions of the study, dynamic triple monitoring combining RTPS, NS and USG decreases intraneural injection and unintentional needle-nerve contact and puncture during a PNB procedure.

Surgical repair of the Achilles tendon can lead to prolonged calf atrophy and functional limitations, even with early weightbearing. The use of neuromuscular electrical stimulation (NMES) has been studied in muscle rehabilitation programs following anterior cruciate ligament repair. Accelerated recovery and pain reduction were noted. The aim of the present study was to evaluate the use of electrical stimulation on maintaining calf muscle cross-sectional area volume and improving patient reported outcome measures following Achilles tendon surgery. Randomized controlled clinical trial. Forty patients were enrolled. All patients had undergone repair of the Achilles tendon. A 4 lead NMES device was applied at time of surgery with both patient and surgeon blinded to activity of the device. All patients followed a standardized postoperative protocol. Group 1 consisted of 20 patients who received protocol specific NMES. Group 2 was the \"sham device\" control group, receiving subtherapeutic electrical stimulation. Preoperative and postoperative calf circumference (2, 6, 12 weeks) and magnetic resonance imaging (MRI) scans (2, 6 weeks) were conducted. Patient-reported functional outcome scores were measured. Of the 40 patients, 23 (57.5%) were male and 17 (42.5%) were female. The mean age was 48.9 years (11.1 standard deviation [SD]) with a mean body mass index of 32.2 kg/m2 (5.7 SD). Calf measurements for Group 1 (39.3 cm and 39.7 cm) were slightly higher compared Group 2 (38.4 cm and 39.2 cm) at 6 and 12 weeks postoperative. Functional scores were similar between Groups 1 and 2 at final follow-up. Foot/Ankle Computer Adaptive Test scores were 55.1 (6.9 SD) versus 58.4(8.6 SD), and American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scores were 82.3 (8.2 SD) and 83.9 (9.3 SD), respectively. The visual analog scale at 12-week visit for Groups 1 and 2 was 8.4 (9.3 SD) and 8.4 (9.1 SD), respectively. This prospective randomized controlled trial was undertaken to quantify and validate the effect and ability of NMES to minimize calf atrophy after acute or chronic repair. No statistically significant difference was found between active NMES and sham control group. There was a trend showing some maintenance of calf volume per MRI study.