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International Journal of Molecular... Aug 2023Hypertension is a prevalent chronic disease associated with an increased risk of cardiovascular (CV) premature death, and its severe form manifests as resistant... (Review)
Review
Hypertension is a prevalent chronic disease associated with an increased risk of cardiovascular (CV) premature death, and its severe form manifests as resistant hypertension (RH). The accurate prevalence of resistant hypertension is difficult to determine due to the discrepancy in data from various populations, but according to recent publications, it ranges from 6% to 18% in hypertensive patients. However, a comprehensive understanding of the pathogenesis and treatment of RH is essential. This review emphasizes the importance of identifying the causes of treatment resistance in antihypertensive therapy and highlights the utilization of appropriate diagnostic methods. We discussed innovative therapies such as autonomic neuromodulation techniques like renal denervation (RDN) and carotid baroreceptor stimulation, along with invasive interventions such as arteriovenous anastomosis as potential approaches to support patients with inadequate medical treatment and enhance outcomes in RH.
Topics: Humans; Hypertension; Therapies, Investigational; Kidney; Autonomic Nervous System
PubMed: 37629095
DOI: 10.3390/ijms241612911 -
Nature Aug 2023The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with...
The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance. Here, we show that antigen-specific avoidance behaviour in inbred mice is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.
Topics: Animals; Mice; Allergens; Avoidance Learning; Hypersensitivity; Immunoglobulin E; Mast Cells; Stomach; Vagotomy; Immunity, Innate; Immunity, Mucosal; Th2 Cells; Cytokines; Leukotrienes; Intestine, Small
PubMed: 37438525
DOI: 10.1038/s41586-023-06188-0 -
Anesthesiology Oct 2023The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty is unclear. This network... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The analgesic effectiveness of contemporary motor-sparing nerve blocks used in combination for analgesia in total knee arthroplasty is unclear. This network meta-analysis was conducted to evaluate the analgesic effectiveness of adding single-injection or continuous adductor canal block (ACB) with or without infiltration of the interspace between the popliteal artery and the capsule of the posterior knee (iPACK) to intraoperative local infiltration analgesia (LIA), compared to LIA alone, after total knee arthroplasty.
METHODS
Randomized trials examining the addition of single-injection or continuous ACB with or without single-injection block at the iPACK to LIA for total knee arthroplasty were considered. The two primary outcomes were area-under-the-curve pain scores over 24 to 48 h and postoperative function at greater than 24 h. Secondary outcomes included rest pain scores at 0, 6, 12, and 24 h; opioid consumption (from 0 to 24 h and from 25 to 48 h); and incidence of nausea/vomiting. Network meta-analysis was conducted using a frequentist approach.
RESULTS
A total of 27 studies (2,317 patients) investigating the addition of (1) single-injection ACB, (2) continuous ACB, (3) single-injection ACB and single-injection block at the iPACK, and (4) continuous ACB and single-injection block at the iPACK to LIA, as compared to LIA alone, were included. For area-under-the-curve 24- to 48-h pain, the addition of continuous ACB with single-injection block at the iPACK displayed the highest P-score probability (89%) of being most effective for pain control. The addition of continuous ACB without single-injection block at the iPACK displayed the highest P-score probability (87%) of being most effective for postoperative function.
CONCLUSIONS
The results suggest that continuous ACB, but not single-injection ACB and/or single-injection block at the iPACK, provides statistically superior analgesia when added to LIA for total knee arthroplasty compared to LIA alone. However, the magnitude of these additional analgesic benefits is clinically questionable.
Topics: Humans; Arthroplasty, Replacement, Knee; Network Meta-Analysis; Pain, Postoperative; Nerve Block; Analgesics, Opioid; Anesthetics, Local
PubMed: 37364292
DOI: 10.1097/ALN.0000000000004667 -
International Journal of Molecular... Aug 2023Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor.... (Review)
Review
Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (α1, α2, β1, β2, and β3) and renal denervation on atherosclerosis. All five types of adrenoceptors are present in arterial blood vessels. α1 blockers inhibit atherosclerosis but increase the risk of heart failure while α2 agonism may protect against atherosclerosis and newer generations of β blockers and β3 agonists are promising therapies against atherosclerosis; however, new randomized controlled trials are warranted to investigate the effectiveness of these therapies in atherosclerosis inhibition and cardiovascular risk reduction in the future. The role of renal denervation in atherosclerosis inhibition in humans is yet to be established.
Topics: Humans; Sympathetic Nervous System; Atherosclerosis; Heart Failure; Hypercholesterolemia; Receptors, Adrenergic; Lipids
PubMed: 37685939
DOI: 10.3390/ijms241713132 -
Journal of the American College of... Nov 2023Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Renal denervation (RDN) reduces blood pressure (BP) in patients with uncontrolled hypertension in the absence of antihypertensive medications.
OBJECTIVES
This trial assessed the safety and efficacy of RDN in the presence of antihypertensive medications.
METHODS
SPYRAL HTN-ON MED is a prospective, randomized, sham-controlled, patient- and assessor-blinded trial enrolling patients from 56 clinical centers worldwide. Patients were prescribed 1 to 3 antihypertensive medications. Patients were randomized to radiofrequency RDN or sham control procedure. The primary efficacy endpoint was the baseline-adjusted change in mean 24-hour ambulatory systolic BP at 6 months between groups using a Bayesian trial design and analysis.
RESULTS
The treatment difference in the mean 24-hour ambulatory systolic BP from baseline to 6 months between the RDN group (n = 206; -6.5 ± 10.7 mm Hg) and sham control group (n = 131; -4.5 ± 10.3 mm Hg) was -1.9 mm Hg (95% CI: -4.4 to 0.5 mm Hg; P = 0.12). There was no significant difference between groups in the primary efficacy analysis with a posterior probability of superiority of 0.51 (Bayesian treatment difference: -0.03 mm Hg [95% CI: -2.82 to 2.77 mm Hg]). However, there were changes and increases in medication intensity among sham control patients. RDN was associated with a reduction in office systolic BP compared with sham control at 6 months (adjusted treatment difference: -4.9 mm Hg; P = 0.0015). Night-time BP reductions and win ratio analysis also favored RDN. There was 1 adverse safety event among 253 assessed patients.
CONCLUSIONS
There was no significant difference between groups in the primary analysis. However, multiple secondary endpoint analyses favored RDN over sham control. (SPYRAL HTN-ON MED Study [Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications]; NCT02439775).
Topics: Humans; Antihypertensive Agents; Bayes Theorem; Prospective Studies; Treatment Outcome; Kidney; Hypertension; Blood Pressure; Sympathectomy; Blood Pressure Monitoring, Ambulatory; Denervation
PubMed: 37914510
DOI: 10.1016/j.jacc.2023.08.045 -
Science Translational Medicine Oct 2023To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable...
To date, there are no approved treatments for the diminished strength and paralysis that result from the loss of peripheral nerve function due to trauma, heritable neuromuscular diseases, or aging. Here, we showed that denervation resulting from transection of the sciatic nerve triggered a marked increase in the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in skeletal muscle in mice, providing evidence that injury drives early expression of this aging-associated enzyme or gerozyme. Treating mice with a small-molecule inhibitor of 15-PGDH promoted regeneration of motor axons and formation of neuromuscular synapses leading to an acceleration in recovery of force after an acute nerve crush injury. In aged mice with chronic denervation of muscles, treatment with the 15-PGDH inhibitor increased motor neuron viability and restored neuromuscular junctions and function. These presynaptic changes synergized with previously reported muscle tissue remodeling to result in a marked increase in the strength of aged muscles. We further found that 15-PGDH aggregates defined the target fibers that are histopathologic hallmarks of human neurogenic myopathies, suggesting that the gerozyme may be involved in their etiology. Our data suggest that inhibition of 15-PGDH may constitute a therapeutic strategy to physiologically boost prostaglandin E2, restore neuromuscular connectivity, and promote recovery of strength after acute or chronic denervation due to injury, disease, or aging.
Topics: Mice; Animals; Humans; Aged; Synapses; Hydroxyprostaglandin Dehydrogenases; Prostaglandins; Muscle, Skeletal; Denervation; Nerve Regeneration
PubMed: 37820010
DOI: 10.1126/scitranslmed.adg1485 -
Annual Review of Medicine Jan 2024Resistant hypertension (RH) is a severe form of hypertension associated with increased cardiovascular risk. Although true RH affects less than 10% of the patients... (Review)
Review
Resistant hypertension (RH) is a severe form of hypertension associated with increased cardiovascular risk. Although true RH affects less than 10% of the patients receiving antihypertensive therapy, the absolute number is high and continues to increase. The workup of these patients requires screening for secondary hypertension and pseudoresistance, including poor adherence to prescribed medicines and the white-coat phenomenon. The treatment of RH consists of lifestyle modifications and pharmacological therapies. Lifestyle modifications include dietary adjustments, weight loss, physical activity, and limiting alcohol consumption; pharmacological therapies include diuretics, mineralocorticoid receptor antagonists, beta blockers, angiotensin receptor-neprilysin inhibitors, and others. Over the last 15 years, interventional approaches have emerged as adjunct treatment options; we highlight catheter-based renal denervation. This review summarizes the rationales and latest clinical evidence and, based thereon, proposes an updated algorithm for the management of RH.
Topics: Humans; Antihypertensive Agents; Hypertension; Life Style
PubMed: 37738507
DOI: 10.1146/annurev-med-050922-052605 -
CMAJ : Canadian Medical Association... Feb 2024
Topics: Humans; Hypertension; Kidney; Denervation
PubMed: 38316459
DOI: 10.1503/cmaj.230745-f -
Current Pain and Headache Reports Apr 2024Trigeminal postherpetic neuralgia (TG-PHN) is a neuropathic pain condition complicating herpes zoster (HZ) attributed to the trigeminal nerve. It poses significant... (Review)
Review
PURPOSE OF REVIEW
Trigeminal postherpetic neuralgia (TG-PHN) is a neuropathic pain condition complicating herpes zoster (HZ) attributed to the trigeminal nerve. It poses significant challenges due to its persistent and debilitating nature. This review explores the clinical characteristics of TG-PHN, analyzes its pathophysiological underpinnings, and addresses existent and potential therapies.
RECENT FINDINGS
TG-PHN is one of the most common and complex PHN locations. It has distinguishing clinical and pathophysiological characteristics, starting with viral triggered injuries to the trigeminal ganglion (TG) and peripheral tissue and involving the ascending and descending brain modulation pathways. Current therapies include vaccines, oral and topical medications, and interventional approaches, like nerve blocks and neurostimulation. This review covers TG-PHN's clinical and physiological components, treatment options, and potential future targets for improved management. By exploring the complexities of this condition, we aim to contribute to developing more effective and targeted therapies for patients suffering from trigeminal PHN.
Topics: Humans; Neuralgia, Postherpetic; Neuralgia; Herpes Zoster; Trigeminal Neuralgia; Nerve Block
PubMed: 38261232
DOI: 10.1007/s11916-023-01209-z -
Journal of Anesthesia Aug 2023To assess the efficacy of pericapsular nerve group (PENG) block combined with lateral femoral cutaneous nerve (LFCN) block in controlling postoperative pain and... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison between pericapsular nerve group (PENG) block with lateral femoral cutaneous nerve block and supra-inguinal fascia iliaca compartment block (S-FICB) for total hip arthroplasty: a randomized controlled trial.
PURPOSE
To assess the efficacy of pericapsular nerve group (PENG) block combined with lateral femoral cutaneous nerve (LFCN) block in controlling postoperative pain and promoting recovery of lower extremity after total hip arthroplasty (THA), and to compare its effectiveness with supra-inguinal fascia iliaca compartment block (S-FICB).
MATERIALS AND METHODS
92 patients undergoing THA with general anesthesia were randomly allocated to receive either a PENG with LFCN block (n = 46) using 30 ml 0.33% ropivacaine (20 ml for PENG block, 10 ml for LFCN block), or an S-FICB (n = 46) using 30 ml 0.33% ropivacaine. The primary outcome was the time to first postoperative walk. The secondary outcomes included intraoperative remifentanil consumption, postoperative hip flexion degree and muscle strength of the operative lower limbs in the supine position, pain scores (static and dynamic), rescue analgesia, postoperative nausea and vomiting (PONV), and nerve block-related complications.
RESULTS
The combination of PENG with LFCN blocks resulted in an earlier first postoperative walking time (19.6 ± 9.6 h vs 26.5 ± 8.2 h, P < 0.01), greater postoperative hip flexion degree at 6 h, 24 h and 48 h (all P < 0.01), and higher muscle strength of the operative lower limbs at 6 h after surgery (P = 0.03) compared to S-FICB. The difference in pain scores (static and dynamic) was only statistically significant at 48 h (P < 0.05). There were no differences in the other outcomes.
CONCLUSIONS
PENG with LFCN blocks is more effective than S-FICB in shortening the time to first postoperative walk and preservation hip motion after THA, which makes it a suitable addition to enhanced recovery programs following surgery.
Topics: Humans; Arthroplasty, Replacement, Hip; Ropivacaine; Femoral Nerve; Nerve Block; Pain, Postoperative; Lower Extremity; Fascia
PubMed: 37043081
DOI: 10.1007/s00540-023-03192-6