Peripheral Blockade Research Articles

Блокада нервов нижней конечности: показания и преимущества

An inadequate approach to the choice of anesthetic care during surgery and in the postoperative period leads to numerous complications, chronic pain, decreased quality of life, as well as to the formation of a negative patient attitude and dissatisfaction with anesthetic care. Currently, there is a constant search for optimal methods of anesthetic management, especially in high-risk patients. Objective. To summarize and present current information on lower limb nerve blockade. Materials and methods. During the research work, an analysis of dissertations on this topic for 2014–2023 was carried out, and Internet resources Elibrary, Cyberleninka, PubMed for the last 9 years were used, since there are not enough literary sources on this topic from 2018 to 2023. Results. An analysis of Russian and foreign literature for 2014–2023 was given, devoted to such a type of anesthetic management as lower limb nerve blockade. Indications, anatomical features, methods, complications in femoral, obturator and sciatic nerve blockades are described. Conclusion. Due to the use of ultrasound navigation, neuromuscular stimulation, catheter technologies, it has become possible to perform peripheral blockades with a minimal risk of complications, as well as to carry out extended peripheral blockades, which allows to speed up the postoperative recovery of patients. Due to the lack of influence of peripheral blockades on hemodynamics, a smaller number of severe complications inherent in central blockades, anesthesiologists increasingly prefer peripheral blockades when choosing a method of anesthetic support for operations on the lower extremities. This type of anesthesia is offered as an alternative to neuraxial blockades, especially in elderly patients with a high class of physical condition.

Role of ASIC3 in Evoking the Exercise Pressor Reflex in Type 1 Diabetes Mellitus Rats

Previous studies have suggested that the exercise pressor reflex is exaggerated in individuals with type 1 diabetes mellitus (T1DM); however, the mechanisms responsible for this altered reflex are poorly understood. Acid-sensing ion channel 3 (ASIC3) likely contributes to this exaggeration as previous studies found that peripheral blockade, as well as functional knockout (KO) of the ASIC3 gene, prevented the exaggeration of exercise pressor reflex in rats with cardiovascular-related diseases. However, whether ASIC3 plays a similar role in the exaggerated exercise pressor reflex in T1DM is currently unknown. Therefore, the purpose of this study was to determine whether ASIC3 contributes to the exaggerated exercise pressor reflex in T1DM rats. We hypothesized that the exaggerated exercise pressor reflex would be attenuated in ASIC3 KO T1DM rats compared to their wild-type (WT) counterparts. To test this, we used adult, male and female Wistar-Kyoto ASIC3 KO (n=3; body weight: 348 ± 84 g) and WT counterparts (n=5; body weight: 318 ± 112 g) rats. Streptozotocin (50 mg/kg) was injected intraperitoneally in fasted anesthetized rats to induce T1DM, and a random blood glucose over 300 mg/dl was used to diagnose diabetes. One week later, the exercise pressor reflex was evoked in unanesthetized, decerebrated rats by statically contracting the hindlimb muscles for 30 s. Peak mean arterial pressure (MAP) and heart rate (HR) were calculated as the highest change (Δ) during 30 s contraction baseline. We found that the peak pressor and cardioaccelerator responses to static contraction, although is not statistically significant, appear to be lower in ASIC3 KO (ΔMAP: 17 ± 14 mmHg; ΔHR: 13 ± 12 bpm), compared to WT rats (ΔMAP: 23 ± 11 mmHg; P=0.26 ΔHR:23 ± 9 bpm; P=0.11). Furthermore, we found that within female rats, the peak pressor and heart rate responses were lower in ASIC3 KO (n=1) rat (ΔMAP: 7 mmHg; ΔHR: 15 bpm) compared to WT rats (n=3) (ΔMAP: 27 ± 12 mmHg; ΔHR: 27 ± 11 bpm). Our preliminary findings suggest that ASIC3 may play a role in the exaggerated exercise pressor reflex in T1DM rats and that sex differences may also be present. Further studies involving larger sample sizes will reveal if trends from the current results become significant. This project was supported by NIH R01HL 166323-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effectiveness of erector spinae plane block in children with pectus excavatum deformity during minimally invasive thoracoplasty with osteosynthesis of the sternocostal complex: a prospective randomized comparative study

BACKGROUND: Despite the widespread use of regional blocks in children, ensuring adequate perioperative pain control during minimally invasive thoracoplasty with osteosynthesis of the sternocostal complex remains a problem. The introduction of ultrasound navigation has allowed specialists to increasingly give preference to peripheral blockades; paravertebral anesthesia has proven to be effective in thoracic surgery. However, safer interfascial blocks, including erector spinae plane block, are rarely used in pediatrics, and there is no evidence base for the effectiveness of the method. OBJECTIVE: Our aim was to compare the effectiveness of erector spinae plane block with paravertebral blockade during minimally invasive thoracoplasty with osteosynthesis of the sternocostal complex in children. MATERIALS AND METHODS: A prospective randomized comparative study of children who underwent minimally invasive thoracoplasty with osteosynthesis of the sternocostal complex was conducted from September 2022 to April 2023. According to the inclusion criteria, the selected 39 children were divided into groups: I — paravertebral blockade, and II — erector spinae plane block. The mean arterial pressure, heart rate during the perioperative period stages, postanesthesia recovery by Aldrete scale and pain intensity by the Wong–Baker scale, and stress response markers (cortisol and lactate) were assessed. RESULTS: No significant differences were observed in the study groups when comparing mean arterial pressure and heart rate at any of the measurement points of the perioperative period (p 0.05). Further, no significant differences were noted between the groups when comparing cortisol and lactate levels (p 0.05). The awakening level was characterized by a short recovery period and did not differ between the groups (p 0.05). The intensity of pain during the observation period did not exceed 5 points on the verbal rating scale in both groups, and the severity of pain was significantly higher in the group with blockade of the erector spinae plane block only 2 hours after surgery (p 0.05).Postoperative nausea and vomiting were more common in children with erector spinae plane block (p 0.05). No other adverse events were recorded. CONCLUSION: Erector spinae plane block is an effective and simple method of regional anesthesia for minimally invasive thoracoplasty with osteosynthesis of the sternocostal complex and can be used as an alternative to paravertebral blockade in children.

Regional anesthesia for hip surgery in children: A review

Hip joint diseases are one of the most common and difficult problems in pediatric orthopedics, often requiring surgical treatment. In children, intra- and postoperative analgesia after hip surgery is more conservative and limited to epidural anesthesia, which has known disadvantages and limitations, despite the high quality of pain relief. Peripheral regional blocks in hip surgery are widespread in adults. Ultrasound navigation makes peripheral blockades safer and more effective. This largely influenced the spread of their use in children and contributed to the introduction of new methods of planar blockades into practice. The authors analyzed studies on the efficacy and safety of modern methods of peripheral regional blockade used in children during hip surgery. The literature search was conducted in the eLibrary, PubMed, and Scopus databases. By using keywords, 750 literature sources were found, and 65 sources relevant to the purpose of the study were included in the review. The lumbar plexus block and fascia iliaca block are the most studied regional techniques in children, which are not inferior in analgesic efficacy to lumbar epidural and caudal anesthesia. A new and promising method of regional anesthesia of the hip is the pericapsular nerve group block, which has been well studied in adults. However, none of the peripheral regional techniques used for analgesia after hip surgery, has not proven its advantages. Further clinical studies are needed to investigate peripheral regional anesthesia techniques and determine their efficacy and safety in pediatric hip surgery.

Regional anesthesia and sickle cell crisis in pediatric patients: An educational-focused review.

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy, affecting approximately 100 000 patients in United States and millions worldwide. Although the mainstay of pain management for VOC remains systemic opioids, given the potential for adverse effects including respiratory depression and hypoxemia, there remains interest in the use of regional anesthetic techniques (neuraxial or peripheral nerve blockade). A systematic search of pubMed, Scopus, and Google Scholar was conducted using the terms sickle cell disease, sickle cell crisis, pain crisis, vaso-occlusive crisis, regional anesthesia, peripheral nerve blockade, and neuraxial anesthesia. We identified 7 publications, all of which were retrospective case series or single case reports, outlining the use of neuraxial anesthesia in a total of 26 patients with SCD. Additionally, we identified 4 publications, including one retrospective case series and 3 single case reports, entailing the use of peripheral blockade in patients with VOC and SCD. The available literature, albeit all retrospective or anecdotal, suggests the potential utility of regional anesthesia to treat pain in patients with SCD. Additional benefits have included avoidance of the potential deleterious physiologic effects of systemic opioids and in one case series, an improvement in respiratory function as judged by pulse oximetry. The anecdotal and retrospective nature of the available reports with an absence of prospective trials limits the evidence based medicine available from which to develop to guidlines for the optimal local anesthetic agent to use, its concentration, the rate of infusion, and the choice of adjunctive agents.

Activation of Type I Interferon and Complement component 3a receptor signaling mediates chronic stress-induced social behavior deficits

Inflammation is involved in the pathophysiology of many neuropsychiatric disorders. Chronic stress increases inflammation and alters protective immune responses. Type I interferons (IFN-I) are key players in the peripheral inflammatory response and are implicated in mood and behavior. In the present study, we investigated the roles of neuroinflammation and synapse loss in IFN-I signaling-mediated social behavior deficits under chronic stress conditions. Our findings show that chronic unpredictable stress (CUS) induces significant increases in serum IFNβ levels. Also, CUS induced microglial activation and synapse loss in the PFC of mice. Peripheral blockade of IFN-I signaling attenuated CUS-induced neuroimmune alterations and social behavioral deficits. Furthermore, complement component 3a receptor 1 (C3ar1) mediates systemic IFNβ-induced neuroinflammation and social behavior deficits. Together, these findings identify a key role of C3ar1 in IFN-I-mediated social behavior deficits under chronic stress conditions.

Stress, immune mechanisms, and mental illness: from etiology to treatment

It is now well-established that a strong relationship exists between psychiatric disorders and disturbances of immune mechanisms at different stages of life. Indeed, a derangement in the expression and function of specific immune elements may predispose and contribute to the development of different psychopathologic conditions and could also represent an important component that must be targeted by therapeutic intervention. The proposed symposium will summarize authoritatively the important recent advances on the immune mechanisms contributing to the etiology of psychiatric disorders, with a specific focus on the role of stress, and it will discuss if and how the effectiveness of therapeutic intervention may depend on the ability to regulate immune mechanisms that are altered under pathologic conditions. The symposium will unfold upon the discussion of preclinical and clinical studies addressing different aspects related to psychiatric disorders. Prof. A. Pillai (University of Texas, U.S.A.) will specifically discuss the roles of neuroinflammation and synapse loss in IFN-I signaling-mediated social deficits under chronic stress conditions. He will discuss how peripheral blockade of IFN-I signaling attenuated stress-induced neuroimmune alterations and social behavioral deficits and also the key role of complement component 3a receptor 1 (C3ar1) in these mechanisms. Along this line, Prof. M.A. Riva (University of Milan, Italy) will show how immune mechanisms and dysregulation of microglial function may contribute to the vulnerability to stress at different life stages, from adolescence to adulthood. Moreover, he will discuss how the normalization of some of these mechanisms following pharmacological intervention may contribute to therapeutic effectiveness in the treatment of different psychiatric disorders characterized, particularly in patients characterized by a higher inflammatory status. At the clinical level, Dr. G. Scaini (University of Texas, U.S.A.) will discuss the interplay between inflammation, stress, and mitochondria in bipolar disorder patients. She will highlight the significant correlation between alterations in mitochondrial proteins and inflammatory markers with a decrease in functional status and an increase in the severity of symptoms. Lastly, Prof. J. Felger (Emory Univ.) will discuss how depressed patients with increased inflammation show altered functional connectivity within the ventral striatum to ventromedial prefrontal cortex reward circuitry in relation to symptoms of anhedonia. These changes can be improved by pharmacological intervention aimed to increase dopamine levels suggesting that functional connectivity in reward circuitry may also serve as a modifiable imaging biomarker for the efficacy of pharmacological and/or behavioral interventions to reverse the impact of inflammation on the brain of depressed subjects.

Combination of peripheral blocks as a part of enhanced rehabilitation in total knee replacement: a prospective comparative open randomized study

BACKGROUND: The patients recovery after total knee replacement (TKR) is long and is associated several potentially serious complications. The optimal solution to this problem is the introduction of regional blocks of the lower limb into anesthesiologic practice, which can contribute to enhanced rehabilitation and fewer complications.
 AIM: To perform a prospective comparative analysis of the anesthesia outcomes of patients who received a combination of prolonged femoral nerve blockade (CFNB) with catheter insertion and infiltration between the popliteal artery and capsule of the knee (IPACK), with the results in patients receiving prolonged epidural analgesia (PEA) as postoperative analgesia for TKR.
 MATERIALS AND METHODS: Eighty patients were included and distributed according to the required planned surgical intervention (TKR). The duration of the inclusion period was 3 months (from March to May 2022). Patients were observed up to 48 h after surgery, with control points every 8 h. The patients were divided into two groups: group 1 (PEA, n=40) underwent subarachnoid anesthesia in combination with PEA, and group 2 (n=40) underwent subarachnoid anesthesia as a combination of CFNB and IPACK. To compare the groups, the following main indicators were used: severity of pain syndrome (visual analog scale [VAS], from 0 to 10 cm), muscle strength on the Medical Research Council (MRC) scale, duration of patients stay in the intensive care unit, duration of hospitalization, and presence of postoperative complications.
 RESULTS: The highest average score for VAS was recorded at 32 h in group 1, and it was 3.6 cm. The lowest average score for VAS (1.11.2 cm) was noted in the first 8 h and after 48 h in group 1. In group 2, this value was 0.91.5 cm in the first 16 h, and at 48 h, the pain syndrome was more pronounced in group 2, making up 2 cm on VAS. Compared with the PEA group, the CFNB group had statistically higher values of the indicators of the motor strength of the leg muscles on the MRC scale at all stages of the study. The PEA group stayed in the intensive care unit statistically significantly longer than the PBN group: 210 (189260) and 180 (154185) min, respectively (p 0.001).
 CONCLUSION: The results of this study showed that the use of multimodal analgesia as a combination of CFNB and IPACK is a reliable anesthetic support for TKR, with an efficiency not inferior to classical epidural analgesia. The use of this combination of peripheral blockades contributes to the early activation and rehabilitation of patients after TKR.

PLACE OF MODERN REGIONAL ANESTHESIA TECHNIQUES IN THE PERIOPERATIVE PERIOD. ADVANTAGES OF LONG-TERM EPIDURAL ANALGESIA WITH ROPIVACAINE

The article deals with the use of modern regional analgesia techniques in the perioperative period. A review of the literature was also conducted, which includes issues of pain control in patients in the perioperative period, characteristics of pain in surgical patients, features of pain relief methods, and certain aspects of the characteristics of local anesthetics. Based on the review of the literature, it can be concluded that neuraxial anesthesia, as well as blockade of peripheral nerves and plexuses have become an integral part of the modern clinical practice of an anesthesiologist. Due to a number of advantages, various methods of local and regional anesthesia are gaining acceptance, and the use of extended catheter techniques for central and peripheral blockades is now recognized as a standard technique in the perioperative management of surgical patients. In modern regional anesthesia and analgesia, both in outpatient settings and in surgical hospitals, the effectiveness and safety of local anesthetics are of fundamental importance

Comparative evaluation of the use of femoral nerve block and adductor canal as a component of early patient activation after knee arthroplasty

BACKGROUND: The number of surgical interventions for the knee joint increases annually due the increase in the total number of patients and the improvement of operation techniques. The provision of modern anesthesiology and intensive care is associated with a positive treatment outcome, which is based on adequate pain relief in the perioperative period, suppressed complications, and reduction in hospital stay. Regional analgesia is a modern and effective method of pain relief after knee surgery. However, the location of peripheral blockade may affect the timing of activation and rehabilitation in these patients.
 AIM: This study aimed to evaluate the use of femoral nerve and adductor canal blockade in the framework of the accelerated recovery program after knee arthroplasty.
 MATERIALS AND METHODS: A prospective, randomized, single-center study included 80 patients who underwent primary knee arthroplasty and were randomly assigned to two clinical groups. Group 1 (n=40) included patients who underwent femoral nerve blockade in the postoperative period, and group 2 (n=40) included patients who underwent adductor canal blockade in the postoperative period. In the postoperative period, the level of pain at rest and during movement was analyzed using a visual analog pain level scale after 6, 12, 24, and 48 hours. The amount of prescribed narcotic analgesic in the postoperative period was recorded, and the total distance that patients were able to walk after 6, 12, 24, and 48 hours was measured.
 RESULTS: For the level of pain at rest and during movement, no significant differences at all time intervals were observed for both groups (p 0.05). No additional prescription of narcotic analgesics was required. Compared with group 1, group 2 covered a significantly greater distance in the first 24 after the operation. After 48 hours, no significant differences were found between the two groups (p 0.05).
 CONCLUSIONS: Femoral nerve and adductor canal blockades provide an adequate level of analgesia after knee arthroplasty. In particular, adductor canal blockade significantly increase the distance of movement by patients in the first 24 hours after surgery.

An assessment of photodynamic therapy efficacy for the treatment of Bowen’s disease of the vulva

Vulvar cancer occupied the 4th place (3–8 %) in the distribution of the malignant neoplasms of female genital organs, although this disease is considered to be rare. In the United States, about 4,000 new cases of vulvar cancer are diagnosed every year, and 850 women die from this cancer. An estimated 650 new cases of this disease are reported per year in Ukraine. One of the precancerous lesions of the vulva along with Paget’s disease is Bowen’s disease, which can progress to squamous cell carcinoma. Photodynamic therapy (PDT) is regarded as an effective method of this disease treatment in the vulva area. The aim of this study was to assess the efficacy and tolerability of PDT in women with Bowen’s disease of the vulva (BDV). Materials and methods. A retrospective study of patients with high-grade Bowen’s disease of the vulva, who were treated with a fundamentally new method of PDT using a systemic photosensitizer photolon, was carried out. During and after PDT, perioperative anesthesia and reduction of the inflammatory process were performed for patients with the help of analgesics, local anesthetics and peripheral blockade of the pudendal nerve (pudendal nerve block). Results. 23 women with a mean age of 38.1 years (range 30–54 years) were included in the study. Based on a number of histological and cytological methods, biopsy and vulvoscopy, the diagnosis of BDV was established, which is currently classified as high-grade squamous intraepithelial lesion of the vulva. Treatment was performed with PDT. The complete response rate of BDV patients with area percentage of the vulvar mucosa lesions of 25 %, 50 % and 100 % was 73.8 % following irradiation after the 1st, 2nd and 3rd series of PDT for 3 months to 1–2 years of follow-up. A partial response was achieved in 13.1 %, while no effect was also reported in 13.1 % of patients. In addition, some patients experienced pain of moderate to severe intensity. Conclusions. Despite the small sample of BDV patients, PDT using both photolon as photosensitizer and an optimized photoirradiation regimen is a potential therapeutic organ-sparing treatment option for patients with high-grade squamous intraepithelial lesions of the vulva. However, there is still a need to study the PDT procedure and the anesthesia choice in combination with various analgesics for patients with a high area percentage of vulvar lesions.

Evaluación de la rehabilitación intensiva con bloqueo continuo del nervio supraescapular para el tratamiento de la capsulitis adhesiva refractaria de hombro. Serie de casos

IntroductionTreatment of refractory adhesive shoulder capsulitis is a challenge. This observational retrospective study evaluated the long-term effectiveness of intensive physiotherapy protocol under a continuous peripheral blockade of the suprascapular nerve (cSSNB). MethodWe reviewed 29 medical records of patients suffering from adhesive capsulitis and treated with intensive physiotherapy under cSSNB during 10 days. The “disabilities of the arm, shoulder and hand” outcome questionnaire (DASH score) and shoulder movements were recorded at the beginning, 10 days after local anesthetic infusion and three months after. ResultsTwenty six patients significant improved shoulder movements after 10 days of treatment. Sixteen patients were followed completely until 3 months after rehabilitation program. Range of four shoulder motion compatible with a normal daily life was acquired in nine patients at three months. There is no significant difference in shoulder motion between the end of LA infusion and at three months. At the end of infusion, DASH score is significantly decreased to 59.3 (n=26), and persists three months 42.1 (n=16). At three months, 33% of the initial population objectively reach the 4 goals, compatible with a correct quality of life. ConclusionRehabilitation under cSSNB is associated with a significant long term improvement in shoulder motion and quality of life in patients with adhesive capsulitis. Randomized controlled trials will be necessary to demonstrate our encouraging results.

Ensuring the effectiveness and safety of peripheral blockades

Adequate analgesia determines the success of the performed surgical intervention. In modern surgery, most of postoperative complications are directly related to ineffective therapy of pain syndrome in the perioperative period. The main principle of modern analgesia is its multicomponence, when analgesia, neurovegetative blockade and relaxation are achieved and potentiated by different drugs and methods. The blockade of nociceptive impulses with a local anesthetic at the transmission stage provides effective, targeted analgesia, hyporefl exia and muscle relaxation, prevents the sensitization of neuroaxial structures, hyperalgesia and the development of postoperative chronic pain syndrome. At the same time, providing analgesia with drugs of central action leads to the ineffectiveness of therapy in 80 % of cases, which has serious consequences.The aim. According to the literature review, to evaluate the effectiveness and safety of peripheral blockades on the example of performing a blockade of the pterygopalatine ganglion.Conclusion. The pterygopalatine blockade has broad indications for use in ophthalmology, which is explained by the complex structure of the pterygopalatine ganglion and the possibility of simultaneous infl uence on sympathetic, parasympathetic and nociceptive innervation. All the presented methods of pterygopalatine blockade performance have their advantages and disadvantages. Ultrasound navigation eliminates technical difficulties and the possibility of damage of the pterygopalatine fossa anatomical structures, ensuring the effectiveness and safety of the pterygopalatine blockade.

Indian Ocean Futures: Implications for U.S. Strategy

Indian Ocean Futures:Implications for U.S. Strategy Zack Cooper (bio) What strategic futures are possible in the Indian Ocean and how will the United States' approach to the region shape and be shaped by these possibilities? By questioning some fundamental assumptions about the Indian Ocean's future, Arzan Tarapore and David Brewster have helped drive an important discussion. In particular, they have initiated a needed debate about the degree to which the United States can rely on its allies and partners in the region, and whether those allies and partners can themselves trust that Washington will devote sufficient attention and resources to the Indian Ocean region. It is now common for U.S. leaders to state that the Indian Ocean is a priority for the United States.1 The growing influence of the Quad, renaming of the Indo-Pacific Command, and adoption of an Asia strategy predicated on the Indo-Pacific concept demonstrate a broadening of the traditional U.S. focus on East Asia.2 What these changes belie, however, is the reality that the United States will have to make some hard choices about prioritization in the years ahead and that, in these debates, the Indian Ocean is unlikely to come out on top.3 Rather than being a priority theater, the Indian Ocean could become an economy of force theater, particularly as the United States draws down forces in Afghanistan and perhaps also the Persian Gulf. In short, the Indian Ocean may not be a top priority for Washington in the years ahead. Of course, the United States will still operate in the region and maintain diplomatic and economic ties with countries bordering [End Page 23] the ocean.4 But U.S. leaders are unlikely to devote scarce defense resources to the region, particularly when military challenges farther east are growing more severe.5 As a result, a division of labor is likely to emerge in which Washington asks its allies and partners around the Indian Ocean to take on much of the burden so that the United States can focus elsewhere. The question remains, however, whether U.S. allies and partners will be willing and able to share that burden. Questioning Assumptions Perhaps the most valuable aspect of futures exercises is the ability to question assumptions that are too often implicit rather than explicit. In this regard, Brewster and Tarapore's scenarios should force a public debate about one key assumption: that the United States will devote substantial resources to the Indian Ocean region in the years ahead. This is not an argument about what the United States should do, but rather about what the United States will do. The strategic logic of a U.S. presence in the Indian Ocean is clear, but whether this accords with political realities and resource constraints is the critical issue at hand. In recent years, there have been several arguments put forward about why the United States should increase the attention it pays to the Indian Ocean region. One popular line among military strategists is that the United States should look to compete with China in the Indian Ocean because the United States has a bigger advantage there than it does closer to China's coastline. In particular, some have suggested that the United States should threaten to conduct a peripheral blockade in the Indian Ocean to deter Chinese military adventurism in East Asia by imposing severe economic costs on China's economy.6 From a strategic standpoint, this makes some sense. The U.S. presence in the Indian Ocean region might force Beijing to devote substantial resources to a distant area where it has some inherent geographic disadvantages, thereby imposing a disproportionate cost on the People's [End Page 24] Liberation Army (PLA), particularly the PLA Navy.7 This approach could also trigger greater balancing by India, which would be threatened by a larger Chinese maritime presence in the Indian Ocean. As a result, some experts have suggested that the United States could avoid vertical escalation in East Asia by relying on the threat of horizontal escalation in the Indian Ocean.8 The reality, however, is that U.S. leaders are likely to see a peripheral campaign of...

Hormonal manipulation in androgen signaling: a narrative review on using novel androgen therapy agents to optimize clinical outcomes and minimize side effects for prostate cancer patients.

Prostate cancer is a significant public health burden and one of the most common cancers globally and in the United States. The current cornerstone of prostate cancer systemic treatment involves the suppression of androgen receptor (AR) signaling, either by reducing the body’s testosterone production or inhibiting its binding to AR and its subsequent gene regulatory network driving carcinogenesis. This signaling pathway plays a central role in both hormone sensitive and castration resistant prostate cancer (CRPC), as evidenced by survival benefit when AR-targeted therapies are applied in the setting of CRPC. With the development of increasingly potent central and peripherally acting androgen targeting agents physicians treating prostate cancer can expect to treat their patients for a longer duration with a larger selection of effective agents. In this setting clinicians are now faced with questions of how to best tailor treatments for the prostate cancer patient to not only maximize overall survival but also optimize the quality of life and mitigate toxicity. In this manuscript we discuss the newer hormone therapy agents for prostate cancer and highlight what they indicate about optimizing medical castration, and the potential value of peripheral blockade.

Peripheral androgen blockade in men with castrate-sensitive biochemical recurrent prostate cancer.

The aim of the study was to evaluate the feasibility of utilizing peripheral androgen blockade in men with biochemical recurrent castrate-sensitive prostate cancer. A registration study to track outcomes of men with biochemical recurrent castrate-sensitive prostate cancer treated with peripheral androgen blockade utilizing concomitant administration of finasteride and bicalutamide. Men were on intermittent peripheral blockade for a median 20.2months, continuous peripheral blockade for a median 6.8months, intermittent triple dose peripheral androgen blockade for a median 10.7months, and continuous triple dose peripheral androgen blockade for 4.4months before failing therapy. Six men (21%) had additional therapies during treatment that included metastasis-directed therapy (5/37, 14%), systemic Lu-177 (2/37, 5%), and salvage RT (1/37, 3%). The median time to progression, which includes time from initiation through all therapies to the initiation of ADT, was 37.6months (IQR 20-74.7). From the start of PAB, median time to castrate resistance was 49.8months (IQR 40.9-NR). After starting ADT, median time to castrate resistance was 8.8months (IQR 4.6-17.7). Our data support the exploration of PAB as a treatment option in carefully selected patients who present with biochemical recurrence after failure of definitive local therapy for prostate cancer.

208-LB: Peripheral CB1 Inverse Agonism Improves Metabolism in DIO Mice Independent of Hepatic FGF21

Obesity is associated with an overactive endocannabinoid system, and selective blockade of CB1R in peripheral tissues, including the liver, reverses HFD-induced metabolic abnormalities by restoring normal lipid and glucose homeostasis and avoid unwanted adverse neuropsychiatric effects. The CB1R inverse agonist JD5037 has been shown equal effective with its brain-penetrant compound in reducing appetite, body weight, hepatic steatosis, and insulin resistance. Fibroblast growth factor-21 (FGF21) has emerged as a major endocrine regulator derived from the liver that reduces adiposity and hepatic steatosis and improves glucose tolerance and insulin sensitivity, with changes similar to those induced by CB1R blockade. Here we investigated whether FGF21 mediate the metabolic effects of CB1R blockade by JD5037 in DIO mice. In C57BL/6J wild-type mice, HFD caused a robust increase in hepatic Fgf21 mRNA and serum FGF21 levels, which were reversed by chronic peripheral CB1R antagonist JD5037 treatment to levels observed in STD or vehicle-treated hepatocyte-specific CB1R-/- (hCB1-/-) mice, indicating activation of CB1R in the liver is largely involved in HFD-induced “FGF21-resistant” state. In contrast, the expression of the FGF21 receptor Fgfr1 and co-receptor β-klotho (Klb) were dramatically reduced by HFD in both epididymal fat and brain tissue in wild-type mice, and these effects were reversed by JD5037 treatment. To address whether FGF21 mediated the metabolic effects of CB1R blockade, we repeated JD5037 treatment in liver-specific FGF21-/- (hFGF21-/-) mice. Surprisingly, JD5037 treatment was almost equally effective in both HFD-fed wild-type and in hFGF21-/- mice in reducing body weight and hepatic steatosis, attenuating hyperinsulinemia and hyperleptinemia. The current data suggest that peripheral CB1R blockade by inverse agonist in obese mice improves insulin sensitivity and energy expenditure independently of hepatic FGF21. Disclosure J. Liu: None. Funding National Institutes of Health

Prolonged regional analgesia in the complex treatment of extensive purulent-necrotic wounds on the background of decompensated arterial and venous insufficiency (case report

Objective:to demonstrate the successful complex treatment of a shin circular wound in a patient with intense pain due to critical limb ischemia and wound infection, which became possible against the background of prolonged peripheral blockade.Materials and methods.A 72-year-old patient with critical ischemia of the right lower extremity was treated for a circular purulent-necrotic wound of the shin leg from November 2016 to April 2017 at the Wounds and Wound Infections Department of FSBI “A. V. Vishnevsky NRC of Surgery” Ministry of Health of Russia. An examination revealed the impossibility of right lower limb arterial insufficiency surgical correction. The patient refused amputation of the lower limb. For the relief of pain, a long-term blockage of the sciatic nerve was used (infusion of ropivacaine 6.0–8.0 mg / hr into the perineural catheter, additional 100 mg ropivacaine boluses were used before performing traumatic daily dressings). The intensity of pain was evaluated on a visual analogue scale (VAS), sought to achieve a pain intensity of not more than 3 points at rest and not more than 4 points on – when moving.Results.Blockade of the sciatic nerve reduced the intensity of pain from 8–10 to 0–3 points, which made it possible to continue treatment. In total, the duration of sciatic nerve catheterization at the stages of treatment was 115 days (18 + 41 + 23 + 32), the maximum duration of one of the peripheral nerve catheterizations was 41 days. Complications associated with nerve catheterization were not observed in the patient. The pain syndrome is stopped, the area of the wound defect is reduced in size. Discharged for outpatient treatment.Conclusion.Long-term peripheral analgesia made it possible to gain time necessary for cleansing the wound surface from necrotic tissues, therapy with drugs that improve arterial blood supply to the limbs, as well as for performing reconstructive and reconstructive operations after the wound process has passed to the reparative stage. Long-term peripheral blockade is a prerequisite for the successful treatment of extensive wounds of the lower extremities caused by insufficient arterial blood supply at the stage of critical limb ischemia, accompanied by intense pain.

Impact of Peripheral α7-Nicotinic Acetylcholine Receptors on Cardioprotective Effects of Donepezil in Chronic Heart Failure Rats.

Pharmacological modulation of parasympathetic activity with donepezil, an acetylcholinesterase inhibitor, improves the long-term survival of rats with chronic heart failure (CHF) after myocardial infarction (MI). However, its mechanism is not well understood. The α7-nicotinic acetylcholine receptor (α7-nAChR) reportedly plays an important role in the cholinergic anti-inflammatory pathway. The purpose of this study was to examine whether blockade of α7-nAChR, either centrally or peripherally, affects cardioprotection by donepezil during CHF. One-week post-MI, the surviving rats were implanted with an electrocardiogram or blood pressure transmitter to monitor hemodynamics continuously. Seven days after implantation, the MI rats (n = 74) were administered donepezil in drinking water or were untreated (UT). Donepezil-treated MI rats were randomly assigned to the following four groups: peripheral infusion of saline (SPDT) or an α7-nAChR antagonist methyllycaconitine (α7PDT), and brain infusion of saline (SBDT) or the α7-nAChR antagonist (α7BDT). After the 4-week treatment, the role of α7-nAChR was evaluated using hemodynamic parameters, neurohumoral states, and histological and morphological assessment. Between the peripheral infusion groups, α7PDT (vs. SPDT) showed significantly increased heart weight and cardiac fibrosis, deteriorated hemodynamics, increased plasma neurohumoral and cytokine levels, and significantly decreased microvessel density (as assessed by anti-von Willebrand factor-positive cells). In contrast, between the brain infusion groups, α7BDT (vs. SBDT) showed no changes in either cardiac remodeling or hemodynamics. Peripheral blockade of α7-nAChR significantly attenuated the cardioprotective effects of donepezil in CHF rats, whereas central blockade did not. This suggests that peripheral activation of α7-nAChR plays an important role in cholinergic pharmacotherapy for CHF.

Protocolo diagnóstico y tratamiento de la tormenta tiroidea

Thyroid storm is a rare and life-threatening disorder appearing within severe thyrotoxicosis with systemic decompensation. Acute events, infection, trauma or surgery are the triggering agents. Clinically, cardiovascular symptoms stand out, especially tachycardia, as well as hyperthermia and central nervous system disorders. Since thyroid hormone levels do not allow to differentiating it from frank hyperthyroidism without complications, diagnosis is based on clinical criteria. Treatment is based on support measures, pharmacological inhibition of the synthesis and release of thyroid hormones (antithyroid, iodinated contrasts or iodine solution, glucocorticoids, cholestyramine), as well as peripheral blockade of the hormone action (beta-adrenergic blockers). Survival depends on early diagnosis (based on diagnostic suspicion) and immediate initiation of specific and support treatment accompanied by the treatment of triggering factor.