Search

With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied. The Study of Muscle, Mobility, and Aging (SOMMA) is a large cohort study with the primary objective to assess how aging muscle biology impacts clinically important traits. Using transcriptomics data from vastus lateralis muscle biopsies in 575 participants we have selected 49 denervation-responsive genes to provide insights to the burden of denervation in SOMMA, to test the hypothesis that greater expression of denervation-responsive genes negatively associates with SOMMA participant traits that included time to walk 400 meters, fitness (VO2peak), maximal mitochondrial respiration, muscle mass and volume, and leg muscle strength and power. Consistent with our hypothesis, increased transcript levels of: a calciumdependent intercellular adhesion glycoprotein (CDH15), acetylcholine receptor subunits (CHRNA1, CHRND, CHRNE), a glycoprotein promoting reinnervation (NCAM1), a transcription factor regulating aspects of muscle organization (RUNX1), and a sodium channel (SCN5A) were each negatively associated with at least 3 of these traits. VO2peak and maximal respiration had the strongest negative associations with 15 and 19 denervation-responsive genes, respectively. In conclusion, the abundance of denervationresponsive gene transcripts is a significant determinant of muscle and mobility outcomes in aging humans, supporting the imperative to identify new treatment strategies to restore innervation in advanced age.

Radiofrequency ablation of the medial branch is commonly used to treat chronic low back pain involving facet joints, which accounts for 12% to 37% of the total cases of chronic low back pain. An adverse effect of this procedure is the denervation of the multifidus muscle, which may lead to its atrophy which can affect the spine and possibly disc degeneration. This study aims to quantify changes in joint angles and loading caused by multifidus denervation after radiofrequency ablation. AnyBody model of the torso was used to evaluate intervertebral joints in flexion, lateral bending, and torsion. Force-dependent kinematics was used to calculate joint angles and forces. These dependent variables were investigated in intact multifidus, unilateral, and bilateral ablations of L3L4, L4L5, and L5S1 joints. The results showed pronounced angular joint changes, especially in bilateral ablations in flexion, when compared with other cases. The same changes' trend from intact to unilaterally then bilaterally ablated multifidus occurred in joint angles of lateral bending. Meanwhile, joint forces were not adversely affected. These results suggest that multifidus denervation after radiofrequency ablation affects spinal mechanics. Such changes may be associated with abnormal tissue deformations and stresses that can potentially alter their mechanobiology and homeostasis, thereby possibly affecting the health of the spine. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of critical limb-threatening ischemia (CLTI) is revascularization. Lumbar sympathectomy (LS) could be attempted when this is not amenable. Using laparoscopic techniques to perform LS adds the advantages of minimally invasive surgery. Methods: Twenty-four patients, presenting with non-reconstructable CLTI and rest pain, were randomly divided into group I (14 patients) who underwent retroperitoneoscopic lumbar sympathectomy (RPLS) and group II (10 patients) who had conventional open lumber sympathectomy (COLS). Results: RPLS patients had shorter hospital stays, fewer intraoperative complications, and less postoperative pain. However, the mean operative time was significantly longer (86.4 ± 9.1 min, p-value: 0.02) in the RPLS group but decreased with each subsequent case after that. The differences in post-operative capillary refill time, ABI, TBI, and TcPO2 were not statistically significant between both groups (p-values: 0.97, 0.13, 0.32, 0.10, respectively). However, the difference in the quality-of-life score was statistically significant; the mean (± SD) SF-36 score increased from 48 ± 6.8 to 81 ± 4.4 (p-value < 0.001) in RPLS group compared to 52 ± 8.8 to 59 ± 1.2 (p-value: 0.52) in COLS group. Conclusion: RPLS is feasible, safe, and has the advantages of minimally invasive surgery: minimal blood loss, less intraoperative complications, shorter hospital stay, and less postoperative pain. However, the operative time in RPLS cases is longer than in the COLS; training on the procedure is recommended to improve the learning curve. [ABSTRACT FROM AUTHOR]

Muscular atrophy accompanied by neuromuscular junction (NMJ) denervation is often observed after long-term chronic diseases and aging and is associated with substantial morbidity and mortality. Here, we report that histone methyltransferase G9a is elevated in the muscle of muscular atrophy model mice and that muscle-specific deficiency of G9a (Ehmt2Ckmm−KO) alleviates muscular atrophy in both aged and denervated mice. Moreover, increased nerve-to-myofiber ratios and increased Agrin-Lrp4-MuSK signaling, which maintains NMJ, are found in aged Ehmt2Ckmm−KO mice. Together, these data suggest that G9a promotes muscular atrophy and disrupts NMJ; thus, inhibiting the G9a level may be a potential therapy for muscular atrophy. [ABSTRACT FROM AUTHOR]

Background Medial branch blocks are used to select patients for cervical facet joint radiofrequency neurotomy (CRFN). Blocks are typically performed under fluoroscopic guidance (ie, fluoroscopy-guided blocks [FLBs]). The validity of ultrasound-guided blocks (USBs) is not well established. No prior research has compared cervical USB validity and FLB validity with CRFN outcome used as the criterion standard. Objective To evaluate cervical USB versus FLB validity with CRFN outcome used as the criterion standard. Methods Demographic and outcome data were extracted from the electronic medical records of 2 affiliated musculoskeletal pain management clinics for all patients between 2015 and 2023 inclusive who had cervical USB leading to CRFN. CRFN outcomes of each USB patient were compared with those of a matched FLB patient from the radiofrequency neurotomy (RFN) outcome database of the same clinics. Matching variables included patient age, sex, pain duration, diagnostic/prognostic block paradigm, and CRFN number. Each patient completed a numeric rating scale (NRS) pain score and Pain Disability Quality-of-Life Questionnaire (PDQQ) just before and 3 months after CRFN. At repeat CRFN, patients provided a retrospective estimate of the duration and average magnitude (percentage) of relief after the CRFN. Results USB and FLB groups were comprised of 27 patients (58 RFNs) and 38 patients (58 RFNs), respectively. Post-RFN NRS pain severity and PDQQ-Spine scores demonstrated comparable (P  > .05) absolute improvements, proportion of patients achieving ≥50% improvement, and attainment of the minimum clinically important difference. Retrospective estimates of pain relief magnitude and duration were also comparable. Conclusions This study finds cervical USB and FLB to be comparably valid as defined by their ability to predict CRFN outcome. Within the limitations of operator competence, USB can be used to select patients for CRFN. [ABSTRACT FROM AUTHOR]

Objective: To compare the prevalence of mental health disorders in individuals with facial synkinesis, facial paralysis alone, and the general population. Study Design: Retrospective cohort. Setting: Eighty‐two health care organizations across the United States. Methods: The TriNetX Research Network was queried from 2011 to 2021 for patients with facial paralysis without synkinesis, facial paralysis and documented synkinesis, and controls, matched for age, sex, race, and ethnicity. Cases included infectious, iatrogenic, or idiopathic facial paralysis. Patients with pre‐existing depression or anxiety were excluded. Two‐year rates of newly diagnosed depression, anxiety, and mental health prescriptions were compared. Results: Among 127,573 patients with facial paralysis, 92.5% (n = 117,976) had facial paralysis alone, and 7.5% (n = 9597) also had documented synkinesis. Compared to controls, patients with facial paralysis alone had increased risks of new depression (8.9% vs 7.3%, P <.001) and anxiety (10.1% vs 9.6%, P <.001), with higher mental health medication rates (16.6% vs 13.1%, P <.001). Patients with documented synkinesis, in comparison to controls, had the highest risks of depression (19.8% vs 8.6%, P <.001), anxiety (20.5% vs 10.5%, P <.001), and prescriptions (28.1% vs 15.8%, P <.001). The 27.8% (n = 2669) of synkinetic patients treated with chemodenervation had lower rates of depression (8.5% vs 23.5%, P <.001), anxiety (9.0% vs 23.8%, P <.001), and prescriptions (21.6% vs 30.0%, P <.001) compared to synkinetic patients who were not. Conclusion: Facial paralysis, particularly synkinesis, is linked to increased mental health disorders. Integrating mental health screening and treatment into a comprehensive approach is crucial. Chemodenervation is associated with decreased mental health disorders in synkinesis, highlighting its therapeutic potential. [ABSTRACT FROM AUTHOR]

Purpose: Preliminary data suggest that gait abnormalities in Parkinson disease (PD) may be associated with sympathetic cardiac denervation. No kinematic gait studies were performed to confirm this observation. We aimed to correlate spatiotemporal kinematic gait parameters with cardiac sympathetic denervation as determined by cardiac [11C]HED PET in PD. Methods: Retrospective database analysis of 27 PD patients with cardiac sympathetic denervation. All patients underwent spatiotemporal kinematic gait assessment (medication 'off' state), cardiac [11C]HED and dopaminergic brain [11C]DTBZ PET scans. We employed a hierarchical regression approach to examine associations between the extent of cardiac denervation, dopaminergic nigrostriatal neurodegeneration, and three gait parameters - velocity, step length and cadence. Results: More extensive cardiac denervation was associated with slower velocity (estimate: -1.034, 95% CI [-1.65, -0.42], p = 0.002), shorter step length (estimate: -0.818, 95% CI [-1.43, -0.21], p = 0.011) and lower cadence (estimate: -0.752, 95% CI [-1.28, -0.23], p = 0.007) explaining alone 30% (Adjusted-R²: 0.297), 20% (Adjusted-R²: 0.202) and 23% (Adjusted-R²: 0.227) of the variability, respecivetly. These associations remained independent of striatal dopaminergic impairment and confounding factors such as age, Hoehn and Yahr (HY) stages, peripheral neuropathy, cognition, and autonomic symptoms. In contrast, striatal dopaminergic denervation was significantly associated with step length (estimate: 0.883, 95% CI [0.29, 1.48], p = 0.005), explaining about 24% of the variability but was dependent of HY stage. Conclusions: More severe cardiac noradrenergic denervation was associated with lower gait velocity, independent of striatal dopaminergic denervation and HY stage, impacting both step length and cadence. These results suggest independent contributions of the peripheral autonomic system degeneration on gait dynsfunction in PD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation, as well as to investigate the potential underlying mechanisms. Methods: Experimental research was conducted using an animal model. Myocardial infarction was induced, followed by defibrillation treatment for ventricular fibrillation cases, and the electrophysiological markers of early recurrence were recorded. Subsequently, a subset of animals underwent sympathetic renal denervation intervention, and the therapeutic effects were compared between the sympathetic renal denervation group and the control group. Electrocardiogram monitoring, histological analysis of myocardial tissue, and neurotransmitter measurements were also performed. Results: Following defibrillation treatment, early recurrence was observed in ventricular fibrillation cases. The electrophysiological markers revealed significantly higher ST segment elevation and T wave changes in the early recurrence group. However, in the sympathetic renal denervation intervention group, the early recurrence rate was significantly reduced, and the electrocardiogram showed improved stability and regularity. Additionally, histological analysis of myocardial tissue demonstrated less cellular damage and lower levels of myocardial fibrosis in the sympathetic renal denervation group. Neurotransmitter measurements revealed a significant decrease in sympathetic nerve activity in the sympathetic renal denervation intervention group. Conclusion: The results of this study indicate an association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation. Sympathetic renal denervation intervention can significantly reduce the early recurrence rate, improve electrocardiogram characteristics, and alleviate myocardial damage and fibrosis. Furthermore, the reduction in sympathetic nerve activity may be one of the potential underlying mechanisms of sympathetic renal denervation intervention. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the effectiveness of circumferential patellar denervation in reducing anterior knee pain (AKP) and improving clinical outcomes after total knee arthroplasty (TKA) without patellar resurfacing. Materials and methods: This prospective, non-randomized, observational study included patients who underwent primary TKA at our institution between August 2023 and January 2024. Patients were divided into two groups: those who received patellar denervation (PD group) and those who did not (NPD group). The primary outcome was the reduction in anterior knee pain (AKP), measured by the Visual Analog Scale (VAS). Secondary outcomes included the Kujala Knee Score, Western Ontario and McMaster Universities Arthritis Index (WOMAC), and range of motion (ROM). Assessments were conducted preoperatively and at 3 and 6 months postoperatively. Results: Four patients in the PD group and five in the NPD group were excluded from the study due to failure to complete follow-up. Thus, 74 female and 16 male patients with a mean age of 67.4 ± 4.2 years were included in the final analysis. There were no significant differences between the two groups with respect to age, sex, side of surgery, height, weight, BMI, grade of patellofemoral osteoarthritis, preoperative ROM, VAS score, Kujala score, and WOMAC score (p: n.s. for all variables). No significant differences were found between the groups for VAS, Kujala, and WOMAC scores at any time point (p: n.s.). Significant improvements in these scores over time were indicated by repeated measures ANOVA (p = 0.001 for both groups). Pairwise comparisons showed significant improvements from preoperative to postoperative months three and six and from postoperative months three to six (p = 0.001 for all comparisons). Both groups experienced decreased knee ROM at third month, which returned to preoperative values at sixth month with no significant differences. No complications were observed during the study. Conclusions: Circumferential patellar denervation does not provide additional benefit in reducing anterior knee pain or improving functional outcomes compared to the non-denervation approach in TKA without patellar resurfacing. Level of evidence: Level III, Prospective comparative study. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effect of patellar denervation (PD) on pain, function and ability to kneel after unicompartmental knee arthroplasty (UKA). Methods: Patients with medial knee osteoarthritis who underwent UKA were prospectively selected. Patients were randomly divided into PD and non-PD groups based on whether patellar denervation was performed. Clinical assessment was performed using the Hospital for Special Surgery (HSS) knee score, Kujiala score, visual analogue scale (VAS) and forgotten joint score (FJS-12), as well as postoperative complications were recorded. The patients' postoperative self-perception and actual ability to perform different kneeling positions were assessed in the two groups. Results: UKA patients treated with PD achieved better Kujiala scores and FJS-12 scores, reduced anterior knee pain and improved kneeling ability postoperatively, validating the effectiveness of PD in UKA. Perception and actual performance of kneeling remained mismatched in PD patients, but performance during different kneeling activities was generally better than in non-PD patients. Trial registration: Clinical Trial Registration: ChiCTR1900025669. Conclusion: Patellar denervation can safely and effectively improve patellofemoral joint function, pain and kneeling ability in the early postoperative period after UKA. [ABSTRACT FROM AUTHOR]

Hypertension is a leading risk factor for cardiovascular morbidity and mortality. Despite the widespread availability of both pharmacological and lifestyle therapeutic options, blood pressure control rates across the globe are worsening. In fact, only 23% of individuals with high blood pressure in the United States achieve treatment goals. In 2023, the US Food and Drug Administration approved renal denervation, a catheter-based procedure that ablates the renal sympathetic nerves, as an adjunctive treatment for patients in whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure. This approval followed the publication of multiple randomized clinical studies using rigorous trial designs, all incorporating renal angiogram as the sham control. Most but not all of the new generation of trials reached their primary end point, demonstrating modest efficacy of renal denervation in lowering blood pressure across a spectrum of hypertension, from mild to truly resistant. Individual patient responses vary, and further research is needed to identify those who may benefit most. The initial safety profile appears favorable, and multiple ongoing studies are assessing longer-term efficacy and safety. Multidisciplinary teams that include hypertension specialists and adequately trained proceduralists are crucial to ensure that referrals are made appropriately with full consideration of the potential risks and benefits. Incorporating patient preferences and engaging in shared decision-making conversations will help patients make the best decisions given their individual circumstances. Although further research is clearly needed, renal denervation presents a novel treatment strategy for patients with uncontrolled blood pressure. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is an incurable, progressive respiratory disease that may have a significant negative impact on the morbidity and mortality of affected patients. A substantial portion of the world's population is affected by COPD, and despite optimal medical management with medications, supplemental oxygen, and pulmonary rehabilitation, many patients are left debilitated because of this disease. Bronchoscopic treatment modalities offer a less-invasive method for the treatment of refractory COPD compared to surgical interventions and have expanded the potential therapeutic options for these patients. Bronchoscopic lung volume reduction is aimed at decreasing the hyperinflation and air trapping that occur in emphysema, and the most studied and successful intervention is endobronchial valve placement. Endobronchial coils, polymeric sealants, and thermal ablation are other researched alternatives. Additional interventional procedures are being investigated for the treatment of the mucus hypersecretion and cough that are associated with the chronic bronchitis phenotype of COPD and include targeted lung denervation, metered dose spray cryotherapy, deobstruction balloon, and bronchial rheoplasty. This review summarizes the most recent evidence pertaining to available therapies for the management of COPD, including chronic bronchitis, with a particular focus on bronchoscopic interventions. [ABSTRACT FROM AUTHOR]

Background: Sympathetic nerve activation followed by obstructive sleep apnea (OSA) accounts for blood pressure elevation. The effectiveness of renal denervation (RDN) in controlling blood pressure in patients with OSA remains controversial. In this systematic review, we tried to pool currently available data to assess the effects of RDN therapy on blood pressure in OSA patients. Methods: We retrieved Pubmed, EMbase and Cochrane Library through 17 May 2023, using the following key words: "renal denervation" and"obstructive sleep apnea". Full articles reporting the change of blood pressure after RDN procedure were included. Results: A total of five studies were included in the meta-analysis. Pooled analysis showed that RDN markedly reduced both 24-h ambulatory systolic blood pressure (24 h-SBP) (Mean difference (MD): -7.54mmHg; 95%Cl: -10.16 to -4.91mmHg; I2 = 0%) and 24-h ambulatory diastolic blood pressure (24 h-DBP) (MD: -5.28mmHg; 95%Cl: -7.35 to -3.22mmHg; I2=0%). Daytime systolic blood pressure (dSBP) was reduced after RDN (MD: -7.54mmHg; 95%Cl: -10.82 to -4.57mmHg; I2 = 54%). With regards to nocturnal blood pressure, we found that RDN resulted in a significant reduction in nighttime systolic blood pressure (nSBP) (MD: -6.91mmHg; 95%Cl: -10.69 to -2.85mmHg; I2=0%). Subgroup analysis showed that dSBP was reduced by 12.00 mmHg, 12.00 mmHg, and 7.25 mmHg at 1 month, 3 months and 6 months, respectively. Our pooled analysis showed that AHI was not significantly changed by RDN. No major compilations were associated with RDN. Conclusions: RDN exerts a considerable blood pressure-lowering effect in hypertensive patients with OSA, which was sustained at least 6 months. [ABSTRACT FROM AUTHOR]

Visual hallucinations can increase the burden of disease for both patients with Parkinson's disease and their caregivers. Multiple neurotransmitters have been implicated in the neuropathology of visual hallucinations, which provide targets for treatment and prevention. In this study, we assessed the association between cholinergic denervation and visual hallucinations in Parkinson's disease in vivo , using PET imaging of the cholinergic system. A total of 38 patients with Parkinson's disease participated in this study. A group of 10 healthy subjects, matched for age, sex and education, was included for comparison. None of the participants used cholinergic drugs. Thirteen patients who had experienced visual hallucinations in the past month (VH+) were compared with 20 patients who had never experienced visual hallucinations in their lives (VH−). Cholinergic system integrity was assessed with PET imaging using 18F-fluoroethoxybenzovesamicol as the tracer. We assessed the differences in tracer uptake between groups by cluster-based analysis and by analysis of predefined regions of interest consisting of the ventral visual stream, the dorsal attentional network, the ventral attentional network and the lateral geniculate nucleus and mediodorsal nucleus of the thalamus. The Parkinson's disease group (n = 38) showed an extensive pattern of decreased tracer uptake throughout the brain compared with the controls (n = 10). Within the Parkinson's disease group, the VH+ group (n = 13) showed a cluster of decreased tracer uptake compared with the VH− group (n = 20), which covered most of the left ventral visual stream and extended towards superior temporal areas. These results were mirrored in the regions of interest-based analysis, in which the VH+ group showed the strongest deficits in the left inferior temporal gyrus and the left superior temporal gyrus compared with the VH− group. Visual hallucinations in Parkinson's disease are associated with a marked cholinergic deficiency in the left ventral visual stream and the left superior temporal lobe, in addition to an extensive global cholinergic denervation in the general Parkinson's disease population. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a major public health issue due to its association with cardiovascular disease risk. Despite the availability of effective antihypertensive drugs, rates of blood pressure (BP) control remain suboptimal. Renal denervation (RDN) has emerged as an effective non-pharmacological, device-based treatment option for patients with hypertension. The multicenter, single-arm, observational Global Paradise™ System (GPS) registry has been designed to examine the long-term safety and effectiveness of ultrasound RDN (uRDN) with the Paradise System in a large population of patients with hypertension. Methods: The study aims to enroll up to 3000 patients undergoing uRDN in routine clinical practice. Patients will be recruited over a 4-year period and followed for 5 years (at 3, 6, and 12 months after the uRDN procedure and annually thereafter). Standardized home BP measurements will be taken every 3 months with automatic upload to the cloud. Office and ambulatory BP and adverse events will be collected as per routine clinical practice. Quality-of-Life questionnaires will be used to capture patient-reported outcomes. Conclusions: This observational registry will provide real-world information on the safety and effectiveness of uRDN in a large population of patients treated during routine clinical practice, and also allow for a better understanding of responses in prespecified subgroups. The focus on home BP in this registry is expected to improve completeness of long-term follow-up and provide unique insights into BP over time. Global Paradise System registry study design. ABP, ambulatory blood pressure; BP, blood pressure; FU, follow-up; M, month; OBP, office blood pressure. [ABSTRACT FROM AUTHOR]

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence. [ABSTRACT FROM AUTHOR]

Introduction: Glucose homeostasis is a physiological process mediated by a variety of hormones. Fibroblast growth factor (FGF) 21 is a protein expressed in the liver, adipose tissue, muscle and pancreas and exerts actions in multiple targets including adipose, liver, pancreas and hypothalamus. The aim of this study was to examine the possible involvement of FGF21 in pancreatic and central control of glucose by measuring reflective changes in the release of insulin and glucagon. Methods: Thirty adult male Wistar Albino rats were divided; Control, PD + aCSF, PD + FGF21 groups (n = 10). Effects of intracerebroventricular (icv) FGF21 administration to pancreatic denervated (PD) rats. Agouti-related protein (AgRP), Pro-opiomelanocortin (POMC) levels and blood glucose homeostasis were investigated. Results: Administration of FGF21 to 3rd ventricle increased food consumption but body weight didn't change significantly. AgRP level increased, pancreatic insulin levels increased, and glucagon level decreased. Conclusion: Central FGF21 administration is effective in regulating blood glucose homeostasis by increasing the amount and efficiency of insulin and changing glucose use. [ABSTRACT FROM AUTHOR]

The cardiac autonomic nervous system plays a key role in maintaining normal cardiac physiology, and once disrupted, it worsens the cardiac disease states. Neuromodulation therapies have been emerging as new treatment options, and various techniques have been introduced to mitigate autonomic nervous imbalances to help cardiac patients with their disease conditions and symptoms. In this review article, we discuss various neuromodulation techniques used in clinical settings to treat cardiac diseases. [ABSTRACT FROM AUTHOR]

Percutaneous neuromodulation is emerging as a promising therapeutic approach for atrial fibrillation (AF). This article explores techniques such as ganglionated plexi (GP) ablation, and vagus nerve stimulation, pinpointing their potential in modulating AF triggers and maintenance. Noninvasive methods, such as transcutaneous low-level tragus stimulation, offer innovative treatment pathways, with early trials indicating a significant reduction in AF burden. GP ablation may address autonomic triggers, and the potential for GP ablation in neuromodulation is discussed. The article stresses the necessity for more rigorous clinical trials to validate the safety, reproducibility, and efficacy of these neuromodulation techniques in AF treatment. [ABSTRACT FROM AUTHOR]

Introduction: Chronic hip pain is a common painful condition in the elderly population. A mini invasive technique that is increasingly being considered for management of CHP is the percutaneous denervation of hip articular branches via radiofrequency ablation. We described a new ultrasound-guided technique based on the combination of 90° ultrasound-guided anterior radiofrequency ablation of the articular branches of femoral nerve, accessory obturator nerve and obturator nerve for anterior hip, combined with 90° ultrasound-guided ablation of the articular branches of the nerve of the quadratus femoris for posterior pericapsular neurolysis of the hip. Material e methods: We retrospectively analyzed the medical records of patients from September 2022 to September 2023 treated for chronic hip pain in the ambulatory of Pain Management, identifying 22 patients who underwent ultrasound guided radiofrequency denervation of anterior hip articular branches alone (Group B); and 22 patients in which was also applied a radiofrequency denervation of the posterior articular branches, in addition to the anterior denervation (Group A). We analysed the pain intensity of both groups measured with numeric rating scale. Result: The combined anterior plus posterior approach ensured that the results obtained were maintained 6 months after the procedure (T3) with excellent pain control and an average NRS of 1455 for group A. While for the group B, with the anterior approach alone, the NRS at six months showed an upward trend with an average NRS of 3818. The dual approach is more effective in pain relief at 6 months with a statistically significant difference in NRS values (p < 0.001). Conclusion: This retrospective observational study highlighted the greater impact of the double approach (anterior plus posterior) in the denervation of the hip joint, compared to anterior neurolysis alone. [ABSTRACT FROM AUTHOR]

Study Design: Systematic review of the literature and subsequent meta-analysis for the development of a new guideline. Objectives: This manuscript summarizes the recommendations from a new clinical guideline published by the German Spine Society. It covers the current evidence on recommendations regarding the indication, test blocks and use of radiofrequency denervation. The guidelines aim is to improve patient care and efficiency of the procedure. Methods: A multidisciplinary working group formulated recommendations based on the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) approach and the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Results: 20 clinical questions were defined for guideline development, with 87.5% consensus achieved by committee members for one recommendation and 100% consensus for all other topics. Specific questions that were addressed included clinical history, examination and imaging, conservative treatment before injections, diagnostic blocks, the injected medications, the cut-off value in pain-reduction for a diagnostic block as well as the number of blocks, image guidance, the cannula trajectories, the lesion size, stimulation, repeat radiofrequency denervation, sedation, cessation or continuation of anticoagulants, the influence of metal hardware, and ways to mitigate complications. Conclusion: Radiofrequency (RF) denervation of the spine and the SI joint may provide benefit to well-selected individuals. The recommendations of this guideline are based on very low to moderate quality of evidence as well as professional consensus. The guideline working groups recommend that research efforts in relation to all aspects of management of facet joint pain and SI joint pain should be intensified. [ABSTRACT FROM AUTHOR]

Background: Hyposmia in Parkinson's disease (PD) had been studied before but had not been detailed by its temporal progression. This study observed how each olfactory subtype evolved in terms of motor symptoms, cardiac sympathetic innervation, and cognition. Methods: Two hundred and three early PD patients were classified as normosmia, hyposmia-converter (hypo-converter), and hyposmia. Their presynaptic monoamine availability at the time of diagnosis was assessed by positron emission tomography imaging using 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane and compared across the subtypes. Motor symptoms were evaluated in all patients, cardiac denervation was examined in 183 patients, and cognition in 195 patients were assessed using a neuropsychological battery. The domains were re-assessed 2–4 times, and the longitudinal data were analyzed to discern the natural course of each subtype. Results: Twenty-nine (14.3%) patients belonged to the normosmia group, 34 (16.7%) to the hypo-converter group, and the rest to the hyposmia (69.0%) group. 85.7% of the total population became hyposmic during an average 3 years of follow-up. The baseline motor symptoms, cardiac denervation, and cognition were comparable across the olfactory subtypes. Across the subtypes, a decline in the presynaptic monoamine densities of the caudate, especially the ventral-anterior subdivisions, correlated inversely with olfaction dysfunction. Over time, motor and cardiac denervation burdens worsened regardless of olfactory subtypes, but hypo-converters experienced faster cognitive deterioration than the other two groups. Conclusions: The results suggest that the olfactory subtypes have differential significance along the disease course, which might reflect the involvement of different neuro-biochemical circuitries. [ABSTRACT FROM AUTHOR]

Introduction: Uncontrolled hypertension is the leading risk factor for global mortality. Most hypertensive patients can be controlled with standard medication combinations, but some may not respond adequately to ≥3 or even to ≥5 antihypertensive agents. Areas covered: In this review, we summarize the recent literature on difficult-to-treat hypertension identified by a Medline search, and we discuss the options for fourth line and subsequent therapy. Expert opinion: It is essential to confirm resistant hypertension with out-of-office blood pressure measurements and to consider lifestyle factors, adherence to medication and secondary causes of hypertension. When true resistant hypertension is confirmed and blood pressure is not controlled with an optimal triple combination, preferably as a fixed dose combination tablet, spironolactone is usually recommended as the fourth medication. Comorbid conditions should be treated as appropriate with sodium-glucose-cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, sacubitril-valsartan or finerenone. Renal denervation appears to be a useful addition to overcome some of the problems of medication adherence. The endothelin antagonist aprocitentan may be a final option in some countries. Of the drugs in development, the RNA based therapeutics that inhibit angiotensinogen synthesis appear to be some of the most promising. [ABSTRACT FROM AUTHOR]

Background: Gap junction remodeling is an important cause of ventricular arrhythmia in heart failure. However, it remains unclear whether renal denervation (RDN) regulates gap junction remodeling in heart failure. To explore the effect of RDN on gap junction remodeling in dogs with high-pacing-induced heart failure. Methods: Fifteen dogs were randomly divided into control (n=5), heart failure (HF) (n=5), and RDN+HF (n=5) group. A high-pacing-induced-heart failure model was established using rapid right ventricular pacing for 4 weeks. The RDN+HF group underwent surgical and chemical ablation of both renal arteries before 4 weeks rapid right ventricular pacing. After 4 weeks, echocardiography, High-Performance Liquid Chromatography-Mass Spectrometry test for norepinephrine and epinephrine, and pathological analysis were performed in the above 3 groups. Further, immunohistochemical staining was used to detect tyrosine hydroxylase, ChaT, connexin 43 (Cx43), and connexin 40 (Cx40). Connexin 43 and Cx40 expression was detected by western blotting. Transmission electron microscopy was used to observe the gap junction. Results: Compared to the control group, myocardial fibrosis and sympathetic hyperactivity were observed in the HF group. Immunohistochemical staining and western blotting showed that Cx40 expression and Cx43 expression was significantly reduced in the HF group. Compared with the HF group, the RDN+HF group showed reduced sympathetic hyperactivity, Cx40 expression, Cx40/Cx43 ratio, and increased Cx43 expression. Conclusion: Renal denervation alleviates gap junction remodeling in high-pacinginduced heart failure dogs. [ABSTRACT FROM AUTHOR]

Immobilization‐induced skeletal unloading results in muscle atrophy and rapid bone loss, thereby increasing the risk of falling and the need for implant therapy in patients with extended bed rest or neuromuscular injuries. Skeletal unloading causes bone loss by altering bone growth and resorption, suggesting that implant performance might be affected. To test this, we focused on early events in implant osseointegration. We used the rat sciatic neurectomy‐induced disuse model under two different settings. In Study 1, 16 Sprague Dawley rats (SD) were separated into control, sham operated+cast immobilization, and sciatic neurectomy+casting groups; titanium implants with multiscale microtextured topography and hydrophilic chemistry (modSLA) were inserted in the distal femoral metaphysis. Neurectomy surgeries and casting were performed at the same surgical setting as implant placement; rats were euthanized 4 weeks post‐implantation. In Study 2, we established the unloaded condition before implantation. A total of 12 SD rats were divided into control and sciatic+femoral neurectomy groups. A total of 24 days after sciatic and femoral neurectomy surgery, rats received implants. Study 2 rats were euthanized at 4 weeks post‐implantation. MicroCT and histomorphometry showed that trabecular bone and osseointegration were reduced when disuse was established before implantation. Osteoblasts isolated from Study 1 sciatic neurectomy tibial bones exhibited impaired differentiation on modSLA culture disks, revealing a possible mechanism responsible for the decreased osseointegration observed in the Study 2 rats. This study addressed the importance of considering the mechanical unloading and muscle function history before implant insertion and suggests that implant performance was reduced due to poor cellular ability to regenerate. [ABSTRACT FROM AUTHOR]

Introduction: Renovascular hypertension (RVH) remains underdiagnosed despite its significant cardiovascular and renal morbidity. Aim: This survey investigated screening and management practices for RVH among hypertensive patients in Italian hypertension centres in a real-life setting. Secondary, we analysed the current spread of renal denervation (RDN) and the criteria used for its eligibility. Methods: A 12 item-questionnaire was sent to hypertension centres belonging to the European Society of Hypertension and to the Italian Society of Hypertension (SIIA) in Italy. Data concerning the screening and management of RVH and of RDN were analysed according to the type of centre (excellence vs non-excellence centres), geographical area and medical specialty. Results: Eighty-two centres participated to the survey. The number of patients diagnosed in each centre with RVH and fibromuscular dysplasia during the last five years was 3 [1;6] and 1 [0;2], respectively. Despite higher rates of RVH diagnosis in excellence centres (p = 0.017), overall numbers remained unacceptably low, when compared to expected prevalence estimates. Screening rates were inadequate, particularly among young hypertensive patients, with only 28% of the centres screening for RVH in such population. Renal duplex ultrasound was underused, with computed tomographic angiography or magnetic resonance angiography reserved for confirming a RVH diagnosis (76.8%) rather than for screening (1.9–32.7%, according to patients' characteristics). Scepticism and logistical challenges limited RDN widespread adoption. Conclusions: These findings underscore the need for improving RVH screening strategies and for a wider use of related diagnostic tools. Enhanced awareness and adherence to guidelines are crucial to identifying renovascular hypertension and mitigating associated cardiovascular and renal risks. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction and objectives: Radiofrequency (RF) renal denervation (RDN) has been shown to be a safe and effective treatment option for patients with uncontrolled hypertension. This analysis sought to explore the cost-effectiveness of this therapy in Spain. Methods: A decision-analytic Markov model projected clinical events, quality-adjusted life years (QALY) and costs over the patients’ lifetime. Treatment effectiveness in the base case analysis was informed by the change in office systolic blood pressure observed in the full cohort of the SPYRAL HTN-ON MED trial (–4.9 mmHg vs sham control). Alternate scenarios were calculated for effect sizes reported in the HTN-ON MED subcohort of patients on 3 antihypertensive medications treated outside the United States, the HTN-OFF MED trial, and the Global SYMPLICITY Registry high-risk and very high-risk cohorts. The analysis was conducted from the Spanish National Health System perspective and a willingness-to-pay a threshold of €25 000 per QALY gained was considered. Results: RF RDN therapy resulted in clinical event reductions (10-year relative risk 0.80 for stroke, 0.88 for myocardial infarction, and 0.72 for heart failure) and a lifetime gain of 0.35 (13.99 vs 13.63) QALYs. Incremental lifetime costs were €5335 (€26 381 vs €21 045), resulting in an incremental cost-effectiveness ratio of €15 057 per QALY gained. Cost-effectiveness was further improved among all the other clinical evidence scenarios. Conclusions: The results of this study suggest that RF RDN can provide a cost-effective alternative in the treatment of uncontrolled hypertension in Spain.

Abstract Purpose The treatment of critical limb-threatening ischemia (CLTI) is revascularization. Lumbar sympathectomy (LS) could be attempted when this is not amenable. Using laparoscopic techniques to perform LS adds the advantages of minimally invasive surgery. Methods Twenty-four patients, presenting with non-reconstructable CLTI and rest pain, were randomly divided into group I (14 patients) who underwent retroperitoneoscopic lumbar sympathectomy (RPLS) and group II (10 patients) who had conventional open lumber sympathectomy (COLS). Results RPLS patients had shorter hospital stays, fewer intraoperative complications, and less postoperative pain. However, the mean operative time was significantly longer (86.4 ± 9.1 min, p-value: 0.02) in the RPLS group but decreased with each subsequent case after that. The differences in post-operative capillary refill time, ABI, TBI, and TcPO2 were not statistically significant between both groups (p-values: 0.97, 0.13, 0.32, 0.10, respectively). However, the difference in the quality-of-life score was statistically significant; the mean (± SD) SF-36 score increased from 48 ± 6.8 to 81 ± 4.4 (p-value

Abstract Muscular atrophy accompanied by neuromuscular junction (NMJ) denervation is often observed after long-term chronic diseases and aging and is associated with substantial morbidity and mortality. Here, we report that histone methyltransferase G9a is elevated in the muscle of muscular atrophy model mice and that muscle-specific deficiency of G9a (Ehmt2 Ckmm−KO) alleviates muscular atrophy in both aged and denervated mice. Moreover, increased nerve-to-myofiber ratios and increased Agrin-Lrp4-MuSK signaling, which maintains NMJ, are found in aged Ehmt2 Ckmm−KO mice. Together, these data suggest that G9a promotes muscular atrophy and disrupts NMJ; thus, inhibiting the G9a level may be a potential therapy for muscular atrophy.

Abstract Objective This study aimed to explore the association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation, as well as to investigate the potential underlying mechanisms. Methods Experimental research was conducted using an animal model. Myocardial infarction was induced, followed by defibrillation treatment for ventricular fibrillation cases, and the electrophysiological markers of early recurrence were recorded. Subsequently, a subset of animals underwent sympathetic renal denervation intervention, and the therapeutic effects were compared between the sympathetic renal denervation group and the control group. Electrocardiogram monitoring, histological analysis of myocardial tissue, and neurotransmitter measurements were also performed. Results Following defibrillation treatment, early recurrence was observed in ventricular fibrillation cases. The electrophysiological markers revealed significantly higher ST segment elevation and T wave changes in the early recurrence group. However, in the sympathetic renal denervation intervention group, the early recurrence rate was significantly reduced, and the electrocardiogram showed improved stability and regularity. Additionally, histological analysis of myocardial tissue demonstrated less cellular damage and lower levels of myocardial fibrosis in the sympathetic renal denervation group. Neurotransmitter measurements revealed a significant decrease in sympathetic nerve activity in the sympathetic renal denervation intervention group. Conclusion The results of this study indicate an association between electrophysiological markers of early recurrence after defibrillation in post-myocardial infarction ventricular fibrillation and the therapeutic effects of sympathetic renal denervation. Sympathetic renal denervation intervention can significantly reduce the early recurrence rate, improve electrocardiogram characteristics, and alleviate myocardial damage and fibrosis. Furthermore, the reduction in sympathetic nerve activity may be one of the potential underlying mechanisms of sympathetic renal denervation intervention.

Abstract Background We aimed to investigate the compression and ischemic effects of two different tourniquet pressures on tissues during surgery show a clinical difference. Methods Patients aged 18–65 years who underwent foot and ankle surgery and applied a tourniquet in a single center between September 2022 and November 2023 were included in this prospective randomized study. Accordingly, tourniquet pressures were applied as limb occlusion pressure (LOP) + 50 mmHg in group 1 (12 patients) and LOP + 100 mmHg in group 2 (12 patients). The time point at which the femoral nerve motor evoked potential (MEP) decreased by 50%, the time point at which the MEP decreased by 100% for all nerves (femoral, tibial, and deep peroneal), and the time point at which all responses returned after the tourniquet was deflated were identified as the time points for analysis. Results There were no differences in demographic data (age, body mass index, and sex) between the two groups. The mean tourniquet pressure was 191 ± 16 mmHg in Group 1 and 247 ± 21 mmHg in Group 2 (p

Abstract Background This study aimed to evaluate the effectiveness of circumferential patellar denervation in reducing anterior knee pain (AKP) and improving clinical outcomes after total knee arthroplasty (TKA) without patellar resurfacing. Materials and methods This prospective, non-randomized, observational study included patients who underwent primary TKA at our institution between August 2023 and January 2024. Patients were divided into two groups: those who received patellar denervation (PD group) and those who did not (NPD group). The primary outcome was the reduction in anterior knee pain (AKP), measured by the Visual Analog Scale (VAS). Secondary outcomes included the Kujala Knee Score, Western Ontario and McMaster Universities Arthritis Index (WOMAC), and range of motion (ROM). Assessments were conducted preoperatively and at 3 and 6 months postoperatively. Results Four patients in the PD group and five in the NPD group were excluded from the study due to failure to complete follow-up. Thus, 74 female and 16 male patients with a mean age of 67.4 ± 4.2 years were included in the final analysis. There were no significant differences between the two groups with respect to age, sex, side of surgery, height, weight, BMI, grade of patellofemoral osteoarthritis, preoperative ROM, VAS score, Kujala score, and WOMAC score (p: n.s. for all variables). No significant differences were found between the groups for VAS, Kujala, and WOMAC scores at any time point (p: n.s.). Significant improvements in these scores over time were indicated by repeated measures ANOVA (p = 0.001 for both groups). Pairwise comparisons showed significant improvements from preoperative to postoperative months three and six and from postoperative months three to six (p = 0.001 for all comparisons). Both groups experienced decreased knee ROM at third month, which returned to preoperative values at sixth month with no significant differences. No complications were observed during the study. Conclusions Circumferential patellar denervation does not provide additional benefit in reducing anterior knee pain or improving functional outcomes compared to the non-denervation approach in TKA without patellar resurfacing. Level of evidence Level III, Prospective comparative study.

With the development of strabismology, the issues of using Botox in various eye movement pathologies are gaining relevance. The literature analysis shows that the data concerning the effectiveness of Botox are ambivalent and as a rule, are based on short-term results. The review presents the data on the efficiency of the botulinum toxin in the treatment of various oculomotor system diseases in comparison with traditional surgical interventions. Indications for such therapy, application techniques, doses and complications are discussed. The generalized modern data on the functional features of the onset of various pathologies in strabismology help assess the potentials of optimizing strabismus treatment with type A botulinum toxin. To search for the data published between 1973 and 2022, select and summarize them we used Google Scholar, PubMed and eLibrary databases.

Abstract Objective The aim of this study was to investigate the effect of patellar denervation (PD) on pain, function and ability to kneel after unicompartmental knee arthroplasty (UKA). Methods Patients with medial knee osteoarthritis who underwent UKA were prospectively selected. Patients were randomly divided into PD and non-PD groups based on whether patellar denervation was performed. Clinical assessment was performed using the Hospital for Special Surgery (HSS) knee score, Kujiala score, visual analogue scale (VAS) and forgotten joint score (FJS-12), as well as postoperative complications were recorded. The patients’ postoperative self-perception and actual ability to perform different kneeling positions were assessed in the two groups. Results UKA patients treated with PD achieved better Kujiala scores and FJS-12 scores, reduced anterior knee pain and improved kneeling ability postoperatively, validating the effectiveness of PD in UKA. Perception and actual performance of kneeling remained mismatched in PD patients, but performance during different kneeling activities was generally better than in non-PD patients. Trial registration Clinical Trial Registration: ChiCTR1900025669. Conclusion Patellar denervation can safely and effectively improve patellofemoral joint function, pain and kneeling ability in the early postoperative period after UKA.

Abstract Background Degeneration of the motoneuron and neuromuscular junction (NMJ) and loss of motor units (MUs) contribute to age‐related muscle wasting and weakness associated with sarcopenia. However, these features have not been comprehensively investigated in humans. This study aimed to compare neuromuscular system integrity and function at different stages of sarcopenia, with a particular focus on NMJ stability and MU properties. Methods We recruited 42 young individuals (Y) (aged 25.98 ± 4.6 years; 57% females) and 88 older individuals (aged 75.9 ± 4.7 years; 55% females). The older group underwent a sarcopenia screening according to the revised guidelines of the European Working Group on Sarcopenia in Older People 2. In all groups, knee extensor muscle force was evaluated by isometric dynamometry, muscle morphology by ultrasound and MU potential properties by intramuscular electromyography (iEMG). MU number estimate (iMUNE) and blood samples were obtained. Muscle biopsies were collected in a subgroup of 16 Y and 52 older participants. Results Thirty‐nine older individuals were non‐sarcopenic (NS), 31 pre‐sarcopenic (PS) and 18 sarcopenic (S). A gradual decrease in quadriceps force, cross‐sectional area and appendicular lean mass was observed across the different stages of sarcopenia (for all P

Background. At present, degenerative lumbar scoliosis is considered as the severest form of degenerative diseases of the spine. As a rule, it occurs at the final stage of the disease development. Advanced age of the patients, high comorbidity and poor bone tissue quality increase risk of complications development at any stage of the treatment. All things considered, the majority of specialists continue their search for minimally invasive surgeries able to improve the life quality of patients with such pathology. Aim of the study — comparative analysis of the surgical treatment results of patients with degenerative lumbar deformities operated using percutaneous and endoscopic denervation techniques. Methods. The study enrolled 58 patients: 42 (72.4%) women and 16 (27.6%) men. Median age accounted for 64 (60-69) years, minimum follow-up period — 2 years. In 28 cases, we performed endoscopic denervation of the lumbar facet joints at the apex of the deformity on both sides (group A), in 30 cases — percutaneous radiofrequency denervation in the appropriate volume (group В). Evaluation of the treatment effectiveness was based on the dynamics of pain syndrome (VAS), patients’ quality of life (ODI), as well as on the frequency of complications and repeated surgical interventions. Results. Mean operative duration and radiation exposure were significantly higher in endoscopic intervention (p0.001). Group A showed an earlier reduction in back pain syndrome compared to group B (p0.001). Assessment of patients’ life quality by ODI showed a high degree of correlation with the level of back pain syndrome. Significant complications of the surgical treatment were not revealed in any patient of both groups. Repeated denervation was performed during the two-year follow-up period in 18 patients (60%) of group B and in 2 patients (7.1%) of group A (p0.001). Analysis of the factors associated with the efficacy of percutaneous denervation showed the significance of deformation magnitude in the frontal plane. Efficiency of percutaneous treatment decreased at the deformity value of 30° and more with a sensitivity of 77% and specificity of 67%. Conclusions. A more pronounced decrease in the intensity of back pain syndrome with preservation of the effect during the whole period of follow-up was noted in patients after endoscopic denervation. However, this was accompanied by a longer duration of intervention and radiation load. According to our data, low efficacy of percutaneous denervation is due to the use of this technique in patients with severe deformity of the lumbar spine.

Abstract Background Renal Denervation (RDN) is a novel non-pharmacological technique to treat hypertension. This technique lowers blood pressure by blocking the sympathetic nerve fibers around the renal artery, then causing a decrease in system sympathetic nerve excitability. This study aimed to visualize and analyze research hotspots and development trends in the field of RDN for hypertension through bibliometric analysis. Methods In total, 1479 studies were retrieved on the Web of Science Core Collection (WoSCC) database from 2004 to 2023. Using CiteSpace (6.2.R4) and VOSviewer (1.6.18), visualization maps were generated by relevant literature in the field of RDN for hypertension to demonstrate the research status and frontiers. Results The number of publications was found to be generally increasing. Europe and the United States were the first countries to carry out research on different techniques and related RDN clinical trials. The efficacy and safety of RDN have been repeatedly verified and gained increasing attention. The study involves multiple disciplines, including the cardiovascular system, peripheral vascular disease, and physiological pathology, among others. Research hotspots focus on elucidating the mechanism of RDN in the treatment of hypertension and the advantages of RDN in appliance therapy. Additionally, the research frontiers include improvement of RDN instruments and techniques, as well as exploration of the therapeutic effects of RDN in diseases with increased sympathetic nerve activity. Conclusion The research hotspots and frontiers reflect the status and development trend of RDN in hypertension. In the future, it is necessary to strengthen international collaboration and cooperation, conduct long-term clinical studies with a large sample size, and continuously improve RDN technology and devices. These measures will provide new options for more patients with hypertension, thereby improving their quality of life.

CT and MRI findings of tongue ptosis and atrophy should alert radiologists to potential pathology along the course of the hypoglossal nerve (cranial nerve XII), a purely motor cranial nerve which supplies the intrinsic and extrinsic muscles of the tongue. While relatively specific for hypoglossal nerve pathology, these findings do not accurately localize the site or cause of denervation. A detailed understanding of the anatomic extent of the nerve, which crosses multiple anatomic spaces, is essential to identify possible underlying pathology, which ranges from benign postoperative changes to life-threatening medical emergencies. This review will describe key imaging findings of tongue denervation, segmental anatomy of the hypoglossal nerve, imaging optimization, and comprehensive imaging examples of diverse pathology which may affect the hypoglossal nerve. Armed with this knowledge, radiologists will increase their sensitivity for detection of pathology and provide clinically relevant differential diagnoses when faced with findings of tongue ptosis and denervation.

Purpose of review: Resistant Hypertension (RH) poses a significant public health challenge, contributing to increased mortality, cardiovascular events and organ damage. Both clinical and experimental research are striving for higher standards in a translational manner to integrate new findings and confirm hypotheses. Considering that many are the aspects of RH that are still under investigation, this review aims to shed light on the advances made in experimental research concerning RH. It seeks to underscore the pivotal role of experimental studies in shaping clinical practices and also explore future perspectives. Recent findings: It is important to emphasize the significance of experimental models, primarily for advancing our understanding: experimental models have greatly contributed to our comprehension of the underlying mechanisms in RH, including factors like sympathetic activation, endothelial dysfunction and structural vessel abnormalities. Secondly, for assessing treatment approaches: animal models have also played a crucial role in evaluating the potential effectiveness of diverse treatment approaches for RH. These encompass both pharmacological options, involving combinations of established drugs or novel pharmaceuticals, and non-pharmacological alternatives, which include surgical procedures like renal denervation, medical devices like baroreceptor stimulators, and lifestyle modifications. Summary: The most lacking component in translational research is the fact that there is no well-established animal model that perfectly replicates RH. Consequently, alternative strategies, including the combination of models, must be considered. What remains clear is that the development of animal models closely mimicking RH holds the promise of providing valuable insights into the essential mechanisms and responses necessary to combat or slow the global progression of RH. [ABSTRACT FROM AUTHOR]

Objective(s): Atrophy of the muscles following denervation can lead to the death of myofibers. This study evaluated the sciatic nerve and tibialis cranialis muscle (TCM) regeneration using scaffold and cells. Materials and Methods: Ninety adult male Wistar rats were divided into six main groups (n=15) and three subgroups (2, 4, and 8 weeks). Groups: control; without surgery, Tr; sciatic nerve transected in silicone tube, S; collagen gel put inside the silicone tube, MC; placed 3x104 mast cells mixed with scaffold, MSC; placed 3x104 mesenchymal stem cells mixed with scaffold, and MC+MSC; 3x104 of each of the mast cell and mesenchymal stem cells along with scaffold. Animals were euthanized and sampled for muscle and nerve histological and nerve immunohistochemical evaluations. Results: Diameter of muscle fibers, ratio of the muscle fiber's nuclei to the fibrocyte nuclei (mn/fn), ratio of the muscle fibers nuclei number to the muscle fiber's number (mn/mf), and ratio of the blood vessels number to the number of muscle fibers (v/mf) in all treatment groups, especially the MC + MSC group, increased compared to the Tr group but the number of mast cells, the percentage of sarcoplasmolysis, and necrosis fibers decreased. Histomorphometric results of the nerve in its various parts and immunohistochemistry results also showed improved nerve conduction, especially in the MC + MSC group. Conclusion: In this study, nerve improvement happened mainly for two reasons: cells and time. So, the most obvious improvement occurred in the group with mast and mesenchymal cells in the 8th week. [ABSTRACT FROM AUTHOR]

Peripheral facial nerve palsy (PFP) is a rare occurrence after dental extraction. Early onset PFP after the procedure can be caused by trauma and/or local anesthesia, whereas delayed onset PFP has more speculative etiologies. The latter has a certain affiliation to Bell's palsy and is therefore primarily treated with corticosteroids, and long-term follow-up is often warranted. This article reports a unique case of a 30-year-old woman developing a delayed onset right-sided PFP after local intraoral anesthetic injection for molar extraction. Facial nerve injury was identified with signs of denervation and neuritis and the patient was treated with nonsteroidal anti-inflammatory drug, corticosteroids, vitamin B supplements, and mime therapy. After 9 months, the patient showed an improvement of the facial muscle activity and went from a grade IV to a grade III on the House-Brackmann grading scale. [ABSTRACT FROM AUTHOR]

Abstract Background Osteoarthritis (OA) contributes increasingly to disability worldwide. There is ample high-quality research on the treatment of knee and hip OA, whereas research on surgical and non-surgical treatment in hand OA is sparse. Limited evidence suggests that education and exercise may improve pain, function, stiffness, and grip strength in hand OA. The established surgical options in hand OA have disadvantages. Prostheses preserve motion but have a high complication rate, whereas fusions decrease function due to limited movement. There is an unmet need for high-quality research on treatment options for hand OA and a need for the development of effective and safe movement-sparing therapies. This study aims to compare the effects of a motion-preserving surgical treatment (denervation of the proximal interphalangeal (PIP) joint) with a patient education and exercise program on patient-reported outcomes and objective function in painful PIP OA. Methods In this parallel-group, two-armed, randomized, controlled superiority trial (RCT), 90 participants are assigned to surgical PIP joint denervation or education and exercise. Pain on load 1 year after intervention is the primary outcome measure. Secondary outcome measures include pain at rest, Patient-Rated Wrist and Hand Evaluation (PRWHE), HQ8 score, EQ5D-5L, objective physical function, complications, two-point discrimination, Mini Sollerman, consumption of analgesics, and the need for further surgery. Assessments are performed at baseline, 3 and 6 months, and 1 year after intervention. Discussion There are no previous RCTs comparing surgical and non-surgical treatment in PIP OA. If patient education plus exercise or PIP denervation improve function, these treatments could be implemented as first-line treatment options in PIP OA. However, if denervation does not achieve better results than non-surgical treatment, it is not justified to use in PIP OA. Trial registration Prospectively registered in ClinicalTrials.gov (NCT05980793) on 8 August 2023. URL https://classic.clinicaltrials.gov/ct2/show/NCT05980793 .

Abstract Background Alzheimer's disease (AD) impairs cognitive functions and peripheral systems, including skeletal muscles. The PS19 mouse, expressing the human tau P301S mutation, shows cognitive and muscular pathologies, reflecting the central and peripheral atrophy seen in AD. Methods We analysed skeletal muscle morphology and neuromuscular junction (NMJ) through immunohistochemistry and advanced image quantification. A factorial Analysis of Variance assessed muscle weight, NCAM expression, NMJ, myofibre type distribution, cross‐sectional areas, expression of single or multiple myosin heavy‐chain isoforms, and myofibre grouping in PS19 and wild type (WT) mice over their lifespan (1–12 months). Results Significant weight differences in extensor digitorum longus (EDL) and soleus muscles between WT and PS19 mice were noted by 7–8 months. For EDL muscle in females, WT weighed 0.0113 ± 0.0005 compared with PS19's 0.0071 ± 0.0008 (P

Abstract Backgrounds Fat infiltration of skeletal muscle has been recognized as a common feature of many degenerative muscle disorders. Retinol binding protein 4 (RBP4) is an adipokine that has been demonstrated to be correlated with the presence and severity of sarcopenia in the elderly. However, the exact role and the underlying mechanism of RBP4 in muscle atrophy remains unclear. Methods Denervation‐induced muscle atrophy model was constructed in wild‐type and RBP4 knockout mice. To modify the expression of RBP4, mice were received intramuscular injection of retinol‐free RBP4 (apo‐RBP4), retinol‐bound RBP4 (holo‐RBP4) or oral gavage of RBP4 inhibitor A1120. Holo‐RBP4‐stimulated C2C12 myotubes were treated with siRNAs or specific inhibitors targeting signalling receptor and transporter of retinol 6 (STRA6)/Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) pathway. Fat accumulation, myofibre cross‐sectional area, myotube diameter and the expression of muscle atrophy markers and myogenesis markers were analysed. Results The expression levels of RBP4 in skeletal muscles were significantly up‐regulated more than 2‐fold from 7 days and sustained for 28 days after denervation. Immunofluorescence analysis indicated that increased RBP4 was localized in the infiltrated fatty region in denervated skeletal muscles. Knockout of RBP4 alleviated denervation‐induced fatty infiltration and muscle atrophy together with decreased expression of atrophy marker Atrogin‐1 and MuRF1 as well as increased expression of myogenesis regulators MyoD and MyoG. By contrast, injection of retinol‐bound holo‐RBP4 aggregated denervation‐induced ectopic fat accumulation and muscle atrophy. Consistently, holo‐RBP4 stimulation also had a dose‐dependent effect on the reduction of C2C12 myotube diameter and myofibre cross‐sectional area, as well as on the increase of Atrogin‐1and MuRF1 expression and decrease of MyoD and MyoG expression. Mechanistically, holo‐RBP4 treatment increased the expression of its membrane receptor STRA6 (>3‐fold) and promoted the phosphorylation of downstream JAK2 and STAT3. Inhibition of STRA6/JAK2/STAT3 pathway either by specific siRNAs or inhibitors could decrease the expression of Atrogin‐1 and MuRF1 (>50%) and decrease the expression of MyoD and MyoG (>3‐fold) in holo‐RBP4‐treated C2C12 myotube. RBP4 specific pharmacological antagonist A1120 significantly inhibited the activation of STRA6/JAK2/STAT3 pathway, ameliorated ectopic fat infiltration and protected against denervation‐induced muscle atrophy (30% increased myofibre cross‐sectional area) in mice. Conclusions In conclusion, our data reveal that RBP4 promotes fat infiltration and muscle atrophy through a STRA6‐dependent and JAK2/STAT3 pathway‐mediated mechanism in denervated skeletal muscle. Our results suggest that lowering RBP4 levels might serve as a promising therapeutic approach for prevention and treatment of muscle atrophy.

To investigate the effects of patellar denervation (PD) and non‐patellar denervation (NPD) after primary total knee arthroplasty (TKA) without patellar resurfacing, this study conducted systematic electronic searches in November 2023 using PubMed, Embase, Web of Science, Cochrane, and Scopus, adhering to Cochrane Collaboration recommendations. Only randomized controlled trials (RCTs) were included. Additionally, a manual search was performed to identify potentially eligible studies from the reference lists of review articles. Two researchers independently conducted literature reviews, data extraction, and risk of bias assessments. The outcome analysis encompassed the incidence of anterior knee pain (AKP), visual analogue scale (VAS), range of motion (ROM), American Knee Society Score (KSS), Oxford Knee Score (OKS), patellar score (PS), complications, and reoperations. Meta‐analysis was executed using RevMan 5.3 software. To enhance the credibility of the study, TSA v0.9 software was utilized to perform power analysis on the overall efficacy of primary and secondary outcomes. Twelve studies involving 1745 patients (1587 knees) were included, with 852 undergoing PD and 893 undergoing NPD. Results indicated a superior reduction in AKP incidence in the PD group compared to the NPD group. Statistically significant differences were observed between PD and NPD in KSS, OKS, and PS. However, the upper limit of the 95% confidence interval for each outcome fell below the minimal clinically important difference (MCID). No significant differences were found in VAS and ROM between PD and NPD. Additionally, PD was not associated with an increased incidence of complications or reoperations. Within 12 months and beyond, PD was proven to be a beneficial intervention in reducing AKP following TKA without patellar resurfacing, achieved without an increase in complications or reoperations. Regarding KSS, OKS, and PS, the minimal advantage achievable through PD may not be clinically significant.

Abstract This case report describes the application of ultrasound renal denervation (uRDN) using the Paradise System in a patient with heart failure with preserved ejection fraction. Initially, the cardiac sympathetic nerve activity of the patient exhibited a late heart/mediastinum (H/M) ratio of 2.00 and a washout rate of 66.0% by cardiac iodine‐123 metaiodobenzylguanidine (123I‐MIBG) scintigraphy. Subsequently, the patient underwent transfemoral uRDN targeting the left, right upper, and right lower renal arteries. At the 6 month follow‐up, no significant change was observed in 123I‐MIBG findings; however, the estimated stressed blood volume (eSBV) decreased from 1722 to 1029 mL/70 kg. At 18 months, 123I‐MIBG findings improved, with the late H/M ratio reaching 2.76 and the washout rate decreasing to 43.1%. This case report highlights the potential of uRDN in reducing eSBV within 6 months and subsequently improving cardiac sympathetic nerve activity at the 18 month follow‐up.

Transurethral resection of the prostate, or other methods to decrease outlet resistance usually leads to relief of symptoms in patients with bladder outlet obstruction (BOO). If symptoms of underactivity persist after normalization of outflow conditions, treatment options are limited. In this review, we hypothesize, based on results from basic research, what might become treatment options for such patients in the future. The primary local treatment will still aim at reducing outlet obstruction. We speculate that local secondary treatment in the future might include transplantation of stem cells or mature bladder ganglion cells into the bladder wall. There has been some success in transplanting ganglion cells into the rat bladder. The ganglion cells will sprout into the surrounding tissue but functional connections between the axons of the transplanted neurons, and the detrusor smooth muscle have so far not been demonstrated. Neurotrophins or neurotrimin might be injected into the bladder wall to increase the sprouting of existing or transplanted neurons. Stem cell transplantation has been performed and improves detrusor function, but it has so far, been difficult to demonstrate transplanted stem cells. BOO, persisting detrusor underactivity, and decreased nerve density are often combined with inflammatory activity of the lower urinary tract. NLR family pyrin domain containing 3 (NLRP3) and its messenger RNA (mRNA) as well as cyclooxygenase-2 (Cox-2) mRNA are increased in obstructed bladders. Systemic treatment with the NLRP3 inhibitor glyburide normalized nerve density in rat bladder, and, to some extent, bladder function. It is unclear whether Cox-2 is involved in the decreased nerve density following obstruction, but Cox-2 mRNA increases 5-fold in obstructed bladder. Future therapy against bladder underactivity remaining following relief of obstruction includes either systemic treatment, perhaps by anti-inflammatory drugs, or local treatment by injection of stem cells, mature ganglion cells, and/or neurotrophins or neurotrimin into the bladder wall.

Background: Osteoarthritis (OA) contributes increasingly to disability worldwide. There is ample high-quality research on the treatment of knee and hip OA, whereas research on surgical and non-surgical treatment in hand OA is sparse. Limited evidence suggests that education and exercise may improve pain, function, stiffness, and grip strength in hand OA. The established surgical options in hand OA have disadvantages. Prostheses preserve motion but have a high complication rate, whereas fusions decrease function due to limited movement. There is an unmet need for high-quality research on treatment options for hand OA and a need for the development of effective and safe movement-sparing therapies. This study aims to compare the effects of a motion-preserving surgical treatment (denervation of the proximal interphalangeal (PIP) joint) with a patient education and exercise program on patient-reported outcomes and objective function in painful PIP OA. Methods: In this parallel-group, two-armed, randomized, controlled superiority trial (RCT), 90 participants are assigned to surgical PIP joint denervation or education and exercise. Pain on load 1 year after intervention is the primary outcome measure. Secondary outcome measures include pain at rest, Patient-Rated Wrist and Hand Evaluation (PRWHE), HQ8 score, EQ5D-5L, objective physical function, complications, two-point discrimination, Mini Sollerman, consumption of analgesics, and the need for further surgery. Assessments are performed at baseline, 3 and 6 months, and 1 year after intervention. Discussion: There are no previous RCTs comparing surgical and non-surgical treatment in PIP OA. If patient education plus exercise or PIP denervation improve function, these treatments could be implemented as first-line treatment options in PIP OA. However, if denervation does not achieve better results than non-surgical treatment, it is not justified to use in PIP OA. Trial registration: Prospectively registered in ClinicalTrials.gov (NCT05980793) on 8 August 2023. URL https://classic.clinicaltrials.gov/ct2/show/NCT05980793. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) is a common subtype of heart failure marked by impaired left ventricular diastolic function and decreased myocardial compliance. Given the limited availability of evidence-based pharmacological treatments for HFpEF, there is a growing interest in nonpharmacological interventions as viable therapeutic alternatives. This review aims to explore the pathophysiology of HFpEF and present recent advancements in nonpharmacological management approaches, encompassing noninvasive therapies, invasive procedures and targeted treatments for comorbidities. An extensive literature review was undertaken to identify and synthesize emerging nonpharmacological treatment options for HFpEF, assessing their potential to enhance patient outcomes. Nonpharmacological strategies, such as vagus nerve stimulation, percutaneous pulmonary artery denervation, renal denervation, transcatheter insertion of atrial shunts and pericardial resection, demonstrate promising potential for alleviating HFpEF symptoms and improving patient prognosis. Moreover, addressing comorbidities, such as hypertension and diabetes, may offer additional therapeutic benefits. These cutting-edge techniques, in conjunction with well-established exercise therapies, pave the way for future research and clinical applications in the field. Nonpharmacological interventions hold promise for advancing HFpEF patient care and fostering a deeper understanding of these treatment approaches, which will facilitate new clinical applications and contribute to the development of more targeted therapies. [ABSTRACT FROM AUTHOR]