Surgical Denervation Research Articles

Activation of brown adipose tissue by a low-protein diet ameliorates hyperglycemia in a diabetic lipodystrophy mouse model

Long-term ad libitum dietary restrictions, such as low-protein diets (LPDs), improve metabolic health and extend the life span of mice and humans. However, most studies conducted thus far have focused on the preventive effects of LPDs on metabolic syndromes. To test the therapeutic potential of LPD, we treated a lipodystrophy mouse model IRFKO (adipose-specific insulin receptor knockout) in this study. We have previously shown that IRFKO mice have profound insulin resistance, hyperglycemia, and whitening of interscapular brown adipose tissue (BAT), closely mimicking the phenotypes in lipoatrophic diabetic patients. Here, we demonstrate that 14-day of LPD (5.1% kcal from protein) feeding is sufficient to reduce postprandial blood glucose, improve insulin resistance, and normalize glucose tolerance in the IRFKO mice. This profound metabolic improvement is associated with BAT activation and increase in whole body energy expenditure. To confirm, we showed that surgical denervation of BAT attenuated the beneficial metabolic effects of LPD feeding in IRFKO mice, including the ‘browning’ effects on BAT and the glucose-ameliorating results. However, BAT denervation failed to affect the body weight-lowering effects of LPD. Together, our results imply a therapeutic potential to use LPD for the treatment of lipoatrophic diabetes.

The Functional Anatomy and Innervation of the Platysma is Segmental: Implications for Lower Lip Dysfunction, Recurrent Platysmal Bands, and Surgical Rejuvenation.

Despite the central role of the platysma in face and neck rejuvenation, much confusion exists regarding its surgical anatomy. This study was undertaken to clarify the regional anatomy of the platysma and its innervation pattern and to explain clinical phenomena, such as the origin of platysmal bands and their recurrence, and the etiology of lower lip dysfunction after neck lift procedures. Fifty-five cadaver heads were studied (16 embalmed, 39 fresh, mean age 75 years). Following preliminary dissections and macro-sectioning, a series of standardized layered dissections were performed, complemented by histology and sheet plastination. In addition to its origin and insertion, the platysma is attached to the skin and deep fascia across its entire superficial and deep surfaces. This composite system explains the age-related formation of static platysmal bands, recurrent platysmal bands after complete platysma transection, and recurrent anterior neck laxity after no-release lifting. The facial part of the platysma is primarily innervated by the marginal mandibular branch of the facial nerve, whereas the submandibular platysma is innervated by the "first" cervical branches, which terminate at the mandibular origin of the depressor labii inferioris. This pattern has implications for postoperative dysfunction of the lower lip, including pseudoparalysis, and potential targeted surgical denervation. This anatomical study, comprised of layered dissections, large histology, and sheet plastination, fully describes the anatomy of the platysma including its bony, fascial, and dermal attachments, as well as its segmental innervation including its nerve danger zones. It provides a sound anatomical basis for the further development of surgical techniques to rejuvenate the neck with prevention of recurrent platysmal banding.

Sensory Nerves inhibit the development of protective anti-melanoma immune response and formation of tertiary lymphoid structures

Abstract Peripheral nervous system (PNS) is an important component of the tumor microenvironment (TME). It has been established that autonomic innervation plays an important role in cancer. However, the effect of the afferent (sensory) neurons on tumor progression remains unclear. Utilizing surgical and chemical skin sensory denervation methods, we showed that afferent neurons supported the growth of melanoma tumors in vivo and demonstrated that sensory innervation limited the activation of effective antitumor immune responses. Precisely, sensory ablation enhanced leukocyte recruitment into tumors, with decreased presence of lymphoid and myeloid immunosuppressive cells and increased activation of T-effector cells within the TME. Denervation further increased T-cell clonality and expanded the B-cell repertoire in the TME. Furthermore, Depletion of CD8+ lymphocytes prevented denervation-restricted tumor growth. Importantly, denervated tumors contained higher densities of mature high endothelial venules (HEV) associated with the formation of classic tertiary lymphoid structures (TLS), which associate with a more favorable melanoma prognosis. Transcriptional profiling of human melanomas confirmed our findings in murine melanoma models. Specifically, we observed that gene signatures of inflammation and the content of neuron-associated transcripts inversely correlated in human primary cutaneous melanomas, with the latter representing a negative prognostic marker of patient overall survival.. Our results suggest that tumor-associated sensory neurons negatively regulate the development of protective antitumor immune responses within the TME, thereby providing a new therapeutic target for melanoma treatment.

Cardiac transplant and exercise cardiac rehabilitation.

Cardiac transplantation is the final therapeutic option for patients with end-stage heart failure. Most patients experience a favorable functional ability post-transplant. However, episodes of acute rejection, and multiple comorbidities such as hypertension, diabetes mellitus, chronic kidney disease and cardiac allograft vasculopathy are common. The number of transplants has increased steadily over the past two decades with 3,817 operations performed in the United States in 2021. Patients have abnormal exercise physiologic responses related to surgical cardiac denervation, diastolic dysfunction, and the legacy of reduced skeletal muscle oxidative capacity and impaired peripheral and coronary vasodilatory reserve resulting from pre-transplant chronic heart failure. Cardiorespiratory fitness is below normal for most patients with a mean peak VO2 of approximately 60% of predicted for healthy persons. Cardiac transplant recipients are therefore excellent candidates for Exercise-Based Cardiac Rehabilitation (CR). CR is safe and is a recommendation of professional societies both before (pre-rehabilitation) and after transplantation. CR improves peak VO2, autonomic function, quality of life, and skeletal muscle strength. Exercise training reduces the severity of cardiac allograft vasculopathy, stroke risk, percutaneous coronary intervention, hospitalization for either acute rejection or heart failure, and death. However, there are deficits in our knowledge regarding CR for women and children. In addition, the use of telehealth options for the provision of CR for cardiac transplant patients requires additional investigation.

Bilateral cardiac sympathetic denervation in patients with congenital long QT syndrome

Long QT syndrome (LQTS) is a potentially lethal yet treatable genetic heart disease for which left cardiac sympathetic denervation (LCSD) is a class I recommendation. Recent reports have suggested bilateral cardiac sympathetic denervation (BiCSD) as the initial surgical denervation therapy in LQTS. The purpose of this study was to determine the frequency and settings in which BiCSD was used in a tertiary referral center with expertise in LCSD. We performed a retrospective review of 234 out of 1638 patients with LQTS who underwent sympathetic denervation (14%) at our institution to identify the subset of patients who underwent BiCSD. Cardiac events (CEs) before LCSD, after LCSD, and after the completion of BiCSD were recorded and defined as being an appropriate implantable cardioverter-defibrillator shock, arrhythmic syncope, or sudden cardiac arrest. Only 11 patients (4.7%; 6 females [55%]) had BiCSD at our institution. Patients who received BiCSD trended toward being younger at diagnosis (6 ± 15 years vs 14 ± 13 years; P = .06) and being more likely to be symptomatic (73% vs 53%; P = .07) than the larger LCSD-only cohort. Continued CEs post-LCSD (3.8 CEs per patient on average) was the predominant determinant to return for BiCSD. Over 60 combined years of follow-up, 4 patients have not had a CE post-BiCSD while the other 7 patients average 3.6 nonlethal CEs. Less than 5% of all patients receiving denervation therapy underwent BiCSD. When BiCSD was chosen, it was almost always done in a staged sequential manner beginning with LCSD first and when driven by the arrhythmogenicity of the LQTS substrate, despite otherwise optimized guideline-directed therapies.

PS-BPB09-5: BROWN ADIPOSE TISSUE DYSFUNCTION PROMOTES METABOLIC DISORDER IN A FAILING HEART.

Objective: Low body temperature predicts poor clinical outcomes in patients with heart failure, however, underlying mechanisms and pathological implications are largely unknown. Brown adipose tissue (BAT) was initially characterized as a heat generating organ, and studies suggest it has crucial roles for maintaining systemic metabolic health. The purpose of this study was to determine whether alteration of BAT function contributes to development of heart failure. Design and method: We generated two murine heart failure models, thoracic aortic constriction (TAC) and myocardial infarction (MI). We analyzed cardiac function, thermogenic response, and pathological findings in the hearts of these mice. We also performed comprehensive metabolomic analyses in the heart, BAT, and plasma samples from sham- and TAC-operated mice. Results: We found murine models with TAC or MI induced BAT dysfunction, and this led to a significant reduction in body temperature. Chronic activation of adrenergic signaling induced apoptosis in brown adipocytes, and surgical denervation of sympathetic nerves innervating BAT improved thermogenic response and cardiac systolic dysfunction. Gain of BAT function model, generated with BAT implantation into peritoneal cavity, improved thermogenesis and ameliorated cardiac dysfunction in TAC. In contrast, systolic function was reduced in genetically BAT dysfunctional model, and this associated with poor survival rate in this model. Metabolomic analyses showed that BAT dysfunction led to an increase of choline and its downstream metabolite, trimethylamine N-oxide (TMAO) that promoted metabolic dysfunction in the failing heart. TMAO administration resulted in a significant reduction in phosphocreatine or ATP level in cardiac tissues, and this was mediated by the suppression of complex IV activity in mitochondria. Genetic or pharmacological inhibition of TMAO production ameliorated cardiac dysfunction during left ventricular pressure overload. Dilated cardiomyopathy patients had lower body temperature, and this associated with an increase in circulating choline and TMAO level. Conclusions: Alteration of BAT function contributes to the development of heart failure via increased TMAO. Our findings suggest that maintenance of BAT homeostasis and reducing TMAO production could be potential next-generation therapies for heart failure.

Back to Life Treatment of Resistant Hypertension- An Update

Resistant hypertension is characterized by severe and persistent high blood pressure that is not normalized even after administering two or more antihypertensive medications, of which one is a diuretic. Although resistant hypertension is commonly encountered in clinics, the prognosis is largely unclear. Mounting evidence indicate that resistant hypertension is a multifactorial pathology of diverse etiology. A wide variety of predisposed factors including age, ethnicity, obesity, obstructive sleep apnea, primary aldosteronism, chronic kidney disease, excessive sympathetic activation and baroreflex dysfunction may be implicated. Although a cocktail of three or four major classes of antihypertensive drugs are recommended for treatment, the benefits of pharmacological interventions is limited in many patients, so surgical denervation of the renal artery is widely practiced to improving patient outcome. Thus, surgical interventions include (i) renal sympathetic denervation, (ii) renal sympathetic innervation, and (iii) device-based carotid baroreceptor electric stimulation may be considered back-to-life options to treat resistant hypertension. Moreover, over the years, these surgical procedures have been refined and fine-tuned to optimize benefits, while minimizing adverse effects. Thus, the current surgical practice has been greatly improved from the time of inception. Therefore, this review will focus on the role of surgical interventions in the treatment and management of resistant hypertension. With the global escalation of hypertension in epidemic proportions and the huge socio-economic burden posed to patients, their families and healthcare systems, it is of utmost importance to improve treatment strategies for all forms of hypertension including resistant hypertension.

Neuromodulation for the Treatment of Refractory Ventricular Arrhythmias

BackgroundNeuromodulation is increasingly recognized as a therapeutic strategy for patients with refractory ventricular arrhythmias (VAs). Percutaneous stellate ganglion blockade (SGB), transcutaneous magnetic stimulation (TcMS), and surgical cardiac sympathetic denervation (CSD) have all been utilized in this setting. ObjectivesThis study sought to characterize contemporary use and outcomes of these neuromodulation techniques for patients with refractory VA. MethodsThis retrospective cohort study included all patients at the Hospital of the University of Pennsylvania with antiarrhythmic drug (AAD)-refractory VA from 2019 to 2021 who were treated with SGB, TcMS, or CSD. ResultsA total of 34 patients (age 61 ± 14 years, 15 polymorphic VAs [44%], refractory to 1.8 ± 0.8 AADs) met inclusion criteria. SGB was performed on 11 patients (32%), TcMS on 19 (56%), and CSD on 7 (21%). Neuromodulation was associated with a reduction in the number of episodes of sustained VAs from 7 [IQR: 4-12] episodes in the 24 hours before the initial neuromodulation strategy to 0 [IQR: 0-1] episodes in the subsequent 24 hours (P < 0.001). During 1.2 ± 1.1 years of follow-up, 21 (62%) experienced recurrent VAs, and among those patients, the median time to recurrence was 3 [IQR: 1-25] days. Outcomes were similar among patients with monomorphic and polymorphic VAs. Among patients who had an acute myocardial infarction within 30 days before neuromodulation, the burden of VAs decreased from 11 [IQR: 7-12] episodes to 0 episodes in the 24 hours after treatment. ConclusionsAutonomic neuromodulation with SGB, TcMS, or CSD in patients with AAD-refractory VAs is safe and results in substantial acute reduction of VA although recurrent arrhythmias are common, and not all patients experience a reduction in arrhythmia burden.

GLP-1 attenuates intestinal fat absorption and chylomicron production via vagal afferent nerves originating in the portal vein

Background/ObjectiveGLP-1R agonists have been shown to reduce fasting and postprandial plasma lipids, both of which are independent risk factors for the development of cardiovascular disease. However, how endogenous GLP-1 – which is rapidly degraded – modulates intestinal and hepatic lipid metabolism is less clear. A vagal gut-brain-axis originating in the portal vein has been proposed as a possible mechanism for GLP-1’s anti-lipemic effects. Here we sought to examine the relationship between vagal GLP-1 signalling and intestinal lipid absorption and lipoprotein production. MethodsSyrian golden hamsters or C57BL/6 mice received portal vein injections of GLP-1(7-36), and postprandial and fasting plasma TG, TRL TG, or VLDL TG were examined. These experiments were repeated during sympathetic blockade, and under a variety of pharmacological or surgical deafferentation techniques. In addition, hamsters received nodose ganglia injections of a GLP-1R agonist or antagonist to further probe the vagal pathway. Peripheral studies were repeated in a novel GLP-1R KO hamster model and in our diet-induced hamster models of insulin resistance. ResultsGLP-1(7-36) site-specifically reduced postprandial and fasting plasma lipids in both hamsters and mice. These inhibitory effects of GLP-1 were investigated via pharmacological and surgical denervation experiments and found to be dependent on intact afferent vagal signalling cascades and efferent changes in sympathetic tone. Furthermore, GLP-1R agonism in the nodose ganglia resulted in markedly reduced postprandial plasma TG and TRL TG, and fasting VLDL TG and this nodose GLP-1R activity was essential for portal GLP-1s effect. Notably, portal and nodose ganglia GLP-1 effects were lost in GLP-1R KO hamsters and following diet-induced insulin resistance. ConclusionOur data demonstrates for the first time that portal GLP-1 modulates postprandial and fasting lipids via a complex vagal gut–brain–liver axis. Importantly, loss or interference with this signalling axis via surgical, pharmacological, or dietary intervention resulted in the loss of portal GLP-1s anti-lipemic effects. This supports emerging evidence that native GLP-1 works primarily through a vagal neuroendocrine mechanism.

Electro-suit treatment of children with unilateral cerebral palsy alters nonlinear dynamics of walking

BackgroundCerebral palsy (CP) is characterized by spasticity and muscle contracture development and associated with mild to severe motor impairments including reduced gait function. Treatment with the Exopulse® suit has been shown to reduce spasticity of the affected muscles and constitutes a non-invasive alternative to pharmaceutical agents and surgical denervation. The present study investigated the effect of systematic treatment with the Exopulse® suit on the nonlinear dynamics and variability of trunk accelerations during walking in children with unilateral CP. MethodsTwelve patients (mean age: 12 years, range 7–17 years) with unilateral CP (GMFCS level 1 and 2) received 24 weeks Exopulse® suit treatment with patient-specific muscle stimulation. Before and after the treatment, the patients completed 4 min treadmill walking while trunk accelerometry was obtained. The nonlinear dynamics was quantified by the largest Lyapunov exponent and the complexity index from the multiscale entropy and movement variability was quantified by the root mean square ratio. Pre- vs post-treatment differences were evaluated by a paired Student's t-test. FindingsThe largest Lyapunov exponent (p-value = 0.041) and the complexity index (p-value = 0.030) of the acceleration in the anterior-posterior direction was significantly lower post-treatment. No other between-trial differences were observed. InterpretationThe present study suggests that 24 weeks of Exopulse® suit treatment alters the nonlinear dynamics but not the variability of the trunk accelerations during walking in children with unilateral CP. The temporal structure of the trunk acceleration in the anterior-posterior direction was altered towards that of healthy individuals.

Sensory Nerves Impede the Formation of Tertiary Lymphoid Structures and Development of Protective Antimelanoma Immune Responses.

Peripheral neurons comprise a critical component of the tumor microenvironment (TME). The role of the autonomic innervation in cancer has been firmly established. However, the effect of the afferent (sensory) neurons on tumor progression remains unclear. Utilizing surgical and chemical skin sensory denervation methods, we showed that afferent neurons supported the growth of melanoma tumors in vivo and demonstrated that sensory innervation limited the activation of effective antitumor immune responses. Specifically, sensory ablation led to improved leukocyte recruitment into tumors, with decreased presence of lymphoid and myeloid immunosuppressive cells and increased activation of T-effector cells within the TME. Cutaneous sensory nerves hindered the maturation of intratumoral high endothelial venules and limited the formation of mature tertiary lymphoid-like structures containing organized clusters of CD4+ T cells and B cells. Denervation further increased T-cell clonality and expanded the B-cell repertoire in the TME. Importantly, CD8a depletion prevented denervation-dependent antitumor effects. Finally, we observed that gene signatures of inflammation and the content of neuron-associated transcripts inversely correlated in human primary cutaneous melanomas, with the latter representing a negative prognostic marker of patient overall survival. Our results suggest that tumor-associated sensory neurons negatively regulate the development of protective antitumor immune responses within the TME, thereby defining a novel target for therapeutic intervention in the melanoma setting.

1353-P: Activation of Brown Adipose Tissue by Low-Protein Diet Ameliorates Hyperglycemia in Lipodystrophic Diabetic Mice Model

Long-term ad libitum dietary restriction such as low-protein diet (LPD) improves metabolic health and extends the life span of mice and possibly humans. However, most studies conducted thus far have focused on the preventive, but not therapeutic, potential of LPDs. Previously we shown that LPD (5.1% kcal from protein) was able to improve postprandial blood glucose values of the lipodystrophic IRFKO (adipose-specific insulin receptor knockout) mice after 14 days with strong activation of interscapular brown adipose tissue (iBAT) and increase energy expenditure. To determine whether iBAT activation was responsible for the hyperglycemia normalization after the LPD treatment, we surgically denervated iBAT of IRFKO mice before LPD treatment. Blood glucose were measured twice a week for up to 4 weeks, at the end of the monitoring mice were subjected to indirect calorimetry assessment (Promethion, Sable Systems) . Our data showed that surgical denervation of iBAT abolished the hyperglycemia normalization effect of LPD in the IRFKO mice. Morphologically, surgical denervation also prevented the ‘browning’ effect of LPD on the whitening iBAT observed in IRFKO mice. In line with the morphological data, LPD failed to induce thermogenic markers including UCP1 and BMP8b in denervated iBAT. In contrast, iBAT denervation has lesser effects on the LPD-induced energy expenditure and circulating FGF21 level, possibly due to compensation by beige fat formation in the inguinal WAT. Together, our data confirms that hyperglycemia normalization caused by LPD on IRFKO is iBAT activation dependent. Our observation suggests that blood glucose could be utilized to fuel LPD-induced iBAT activation as a mechanism for amino acid homeostasis. Further experimentation needs to be done in order to narrow down the mechanism driving this phenomenon. Taken together, our data suggest that short-term LPD could be a potential strategy for the treatment of metabolic syndrome. Disclosure M.D.Munoz: None. A.Zamudio: None. M.A.Mccann: None. C.Liew: None. Funding NIH RDK109015A1

PO-698-06 NEUROMODULATION FOR THE TREATMENT OF REFRACTORY VENTRICULAR ARRHYTHMIAS

Neuromodulation of sympathetic tone is increasingly recognized as a therapeutic strategy for patients with refractory ventricular arrhythmias (VA). Percutaneous stellate ganglion blockade (SGB), transcutaneous magnetic stimulation (TcMS), and surgical sympathetic denervation (SD) have all been utilized in this setting. To describe our experience with autonomic neuromodulation for the treatment of refractory VA. This retrospective cohort study included all patients at the Hospital of the University of Pennsylvania with antiarrhythmic drug (AAD) refractory VA from 2019-2021 who were treated with SGB, TcMS, or SD. A total of 33 patients (age 60±14 years, 25 (76%) male, 14 (42%) polymorphic VA) met inclusion criteria. VA were refractory to 1.8±0.8 AAD. SGB was performed on 11 patients (33%), TcMS on 19 (56%), and SD on 6 (18%). Two patients underwent both SGB and SD, and one patient underwent both SGB and TcMS. Two patients who underwent SGB had the procedure repeated after 1 and 5 days respectively due to recurrent VA. SGB was performed on the left-side in 5 (46%) and was bilateral in 6 (54%) patients. SGB was guided by ultrasound in 9 (82%), fluoroscopy in 3 (27%), or anatomic landmarks with no imaging in 1 (9%). Lidocaine was the most common agent used (n=9). SD was performed on the left-side in 1 (17%) and was bilateral in 5 (83%). SD was performed via thoracotomy in 1 (17%) due to body habitus and via video-assisted thoracoscopic surgery in 5 (83%). There were no complications of any neuromodulation approach. Neuromodulation was associated with a reduction in the number of episodes of sustained VA from 10.4±11.3 episodes in the 24-hours prior to the initial neuromodulation strategy to 1.3±3.1 episodes in the subsequent 24-hours (p<0.001) with no decrease in 5 patients (15%). During 602±250 days of follow-up, 18 (55%) experienced recurrent ventricular arrhythmias and among those patients, the time to recurrence was 22±44 days. Recurrence was similar in patient in monomorphic (58%) vs polymorphic VA (50%). Autonomic neuromodulation with SGB, TcMS, or SD in patients with AAD refractory VT is safe and results in substantial acute reduction of VA burden in the majority although recurrent arrhythmias are common and not all patients experience a reduction in arrhythmia burden.

PO-656-07 BILATERAL CARDIAC SYMPATHETIC DENERVATION IN PATIENTS WITH CONGENITAL LONG QT SYNDROME

Long QT syndrome (LQTS) is a potentially lethal, yet treatable genetic heart disease for which left cardiac sympathetic denervation (LCSD) is a class I recommendation by the ACC, AHA, and HRS as either a treatment intensifier for severe disease or a treatment alternative for side effects to standard drug therapy. Recent reports suggest bilateral CSD (BiCSD) as the initial surgical denervation therapy in LQTS.

CT-Guided Cooled Radiofrequency Denervation for Chronic Arthritis Pain of the Hip and Shoulder.

The paradigm in the treatment of arthritis pain is shifting for previously open surgical denervations of the hip and shoulder, as it already has for the geniculate nerves in knee arthritis. Interventional radiology is poised to contribute to this space with the use of CT guidance to provide safe, fast, and effective targeting of the target nerves for unequivocal diagnostic nerve block and definitive cooled radiofrequency denervation. The authors provide the background of which nerves are targeted for hip and shoulder denervation and the normal CT appearance of these blocks.

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Surgical management of chronic scrotal pain: a review of the current literature.

Chronic scrotal pain (CSP) may be due to an identifiable cause, may be multifactorial, or may be idiopathic. Successful treatment often requires multimodal therapy with a multidisciplinary approach. Conservative options may be offered initially, but if symptoms fail to improve with conservative interventions, more invasive therapies may be required. A nerve block may be attempted and patients who experience improvement in pain following nerve blocks may be good candidates for surgical denervation of the spermatic cord. Alternative surgical treatment options including proximal nerve blocks, neuromodulation, cryoablation, vasectomy reversal, varicocelectomy, and even orchiectomy have been described. The aim of this review is to discuss the treatment options for CSP with a focus on surgical treatment options.

Ultrasound-Guided Thoracodorsal Nerve Block for Post-Breast Reconstruction Discomfort.

CASE PRESENTATION A 76-yr-old woman with prediabetes and estrogen receptor–positive breast cancer diagnosed 2 yrs ago underwent a bilateral mastectomy and breast reconstruction with tissue expander and latissimus dorsi flap 1 yr ago. After the procedure, the patient developed constant muscle hyperactivity and a tight band-like feeling in the lateral aspect of the reconstructed breast flap. Subsequently, the tissue expanders were removed without a significant improvement of her symptoms. She denied numbness, tingling, lancinating, electricity-like pain, or pins/needles sensation. She tried physical therapy, a transcutaneous electrical nerve stimulation unit, and oral baclofen without significant relief. Ultrasound-guided thoracodorsal nerve block with 1% lidocaine and 0.25% bupivacaine was performed with consideration for the positive motor symptoms and lack of cutaneous sensory symptoms in the distribution of the latissimus dorsi flap, as illustrated in the Figures 1 and 2. The patient reported 100% relief of symptoms for 5 days and approximately 50% relief of symptoms for 2 wks. Repeated ultrasound-guided injection as per the patient’s request reproduced a similar pattern of symptom relief.FIGURE 1: Ultrasonographic images of the thoracodorsal nerve (yellow arrow) and surrounding structures using an 8- to 15-MHz linear array probe.FIGURE 2: Ultrasonographic-guided perineural block of thoracodorsal nerve using in-plane approach.More than 250,000 women were diagnosed with breast cancer in 2017 and more than 100,000 breast reconstruction procedures were performed.1,2 Latissimus dorsi flaps are frequently used as an option for salvage reconstruction given presence of healthy muscle tissue and consistent vascular supply. As high as 10% of patients who have latissimus dorsi flaps complain of persistent postsurgical pain lasting months or years. Complaints after latissimus dorsi–based reconstruction include abnormal muscle movement, breast deformity, significant muscle tone at rest, and pain, as illustrated in this case.1 Regarding peripheral nerve lesions, intercostobrachial cutaneous, intercostal, and long thoracic nerve injuries are well-known contributors to post–breast surgery pain syndrome.3,4 The thoracodorsal nerve is often underrecognized as the culprit for post–breast surgery pain syndrome. Surgical denervation of the thoracodorsal nerve was proposed but remains controversial because of potential detriments to the reconstruction.1 This case highlights the diagnostic and therapeutic role of ultrasound-guided thoracodorsal nerve blocks for the evaluation and management of post–breast surgery pain and discomfort.

Blood Pressure Regulation by the Carotid Sinus Nerve: Clinical Implications for Carotid Body Neuromodulation.

Chronic carotid sinus nerve (CSN) electrical modulation through kilohertz frequency alternating current improves metabolic control in rat models of type 2 diabetes, underpinning the potential of bioelectronic modulation of the CSN as a therapeutic modality for metabolic diseases in humans. The CSN carries sensory information from the carotid bodies, peripheral chemoreceptor organs that respond to changes in blood biochemical modifications such as hypoxia, hypercapnia, acidosis, and hyperinsulinemia. In addition, the CSN also delivers information from carotid sinus baroreceptors—mechanoreceptor sensory neurons directly involved in the control of blood pressure—to the central nervous system. The interaction between these powerful reflex systems—chemoreflex and baroreflex—whose sensory receptors are in anatomical proximity, may be regarded as a drawback to the development of selective bioelectronic tools to modulate the CSN. Herein we aimed to disclose CSN influence on cardiovascular regulation, particularly under hypoxic conditions, and we tested the hypothesis that neuromodulation of the CSN, either by electrical stimuli or surgical means, does not significantly impact blood pressure. Experiments were performed in Wistar rats aged 10–12 weeks. No significant effects of acute hypoxia were observed in systolic or diastolic blood pressure or heart rate although there was a significant activation of the cardiac sympathetic nervous system. We conclude that chemoreceptor activation by hypoxia leads to an expected increase in sympathetic activity accompanied by compensatory regional mechanisms that assure blood flow to regional beds and maintenance of hemodynamic homeostasis. Upon surgical denervation or electrical block of the CSN, the increase in cardiac sympathetic nervous system activity in response to hypoxia was lost, and there were no significant changes in blood pressure in comparison to control animals. We conclude that the responses to hypoxia and vasomotor control short-term regulation of blood pressure are dissociated in terms of hypoxic response but integrated to generate an effector response to a given change in arterial pressure.

Durable strong efficacy and favorable long-term renal safety of the anatomically optimized distal renal denervation according to the 3 year follow-up extension of the double-blind randomized controlled trial

BackgroundHistorical reports on surgical renal denervation consistently describe renal plexus as a triangle or fan-like structure converging at the kidney gate. Following that anatomy, we developed a distal mode of radiofrequency renal denervation (RDN) mainly in segmental branches of the renal artery and confirmed its superior efficacy over the conventional main trunk procedure in a 6-months double-blind randomized controlled trial (NCT02667912). To assess the long-term effects of distal RDN we extended the follow-up of our study to three years. MethodsBP, serum creatinine, eGFR were measured one and three years after randomization; major adverse renal events were assessed over the entire study period. The blinding was maintained over the entire three-year study period. FindingsOf 55 randomized patients, 47 (23/24, distal/main trunk RDN, respectively) were assessed at one year and 39 (21/18) at three years post-procedure. Twenty-four-hour ambulatory systolic BP remained powerfully lowered after distal RDN both at one- and three-years assessments(mean change from baseline: -18.0, 95% CI -27.6 to -8.5; p<0.05 and -16·9, 95% CI -27·3 to -6·5; p<0·05, mmHg, respectively. This was accompanied by a moderate drop in eGFR at one year: -8·9 ml/min/m2, 95% CI -14·8 to -3·1; p<0·05, which, however, subsequently decreased in size at three years: -6·5, 95% CI -13·2 to 0·3; p>0·05. After main trunk RDN, the decrease of 24h systolic BP was quite moderate at one year: -12·1, 95% CI -19·2 to -5·0; p<0·05, and further weakened at three-year assessment: -8·5, 95% CI -19·7 to 2·2; p>0.05. eGFR was almost unchanged at one year: -1·3, 95% CI -6·6 to 4·0; p>0·05, but significantly decreased at three years: -5·0, 95% CI -9·6 to -0·3; p<0·05. InterpretationOur data demonstrate the durable strong BP-lowering efficacy and favorable long-term renal safety of distal RDN.