Prolonged Blockade Research Articles

Retinoic acid-mediated homeostatic plasticity drives cell type-specific CP-AMPAR accumulation in nucleus accumbens core and incubation of cocaine craving.

Incubation of cocaine craving, a translationally relevant model for the persistence of drug craving during abstinence, ultimately depends on strengthening of nucleus accumbens core (NAcc) synapses through synaptic insertion of homomeric GluA1 Ca2+-permeable AMPA receptors (CP-AMPARs). Here we tested the hypothesis that CP-AMPAR upregulation results from a form of homeostatic plasticity, previously characterized in vitro and in other brain regions, that depends on retinoic acid (RA) signaling in dendrites. Under normal conditions, ongoing synaptic transmission maintains intracellular Ca2+ at levels sufficient to suppress RA synthesis. Prolonged blockade of neuronal activity results in disinhibition of RA synthesis, leading to increased GluA1 translation and synaptic insertion of homomeric GluA1 CP-AMPARs. Using slice recordings, we found that increasing RA signaling in NAcc medium spiny neurons (MSN) from drug-naïve rats rapidly upregulates CP-AMPARs, and that this pathway is operative only in MSN expressing the D1 dopamine receptor. In MSN recorded from rats that have undergone incubation of craving, this effect of RA is occluded; instead, interruption of RA signaling in the slice normalizes the incubation-associated elevation of synaptic CP-AMPARs. Paralleling this in vitro finding, interruption of RA signaling in the NAcc of 'incubated rats' normalizes the incubation-associated elevation of cue-induced cocaine seeking. These results suggest that RA signaling becomes tonically active in the NAcc during cocaine withdrawal and, by maintaining elevated CP-AMPAR levels, contributes to the incubation of cocaine craving.

Homeostatic Synaptic Plasticity of Miniature Excitatory Postsynaptic Currents in Mouse Cortical Cultures Requires Neuronal Rab3A.

Following prolonged activity blockade, amplitudes of miniature excitatory postsynaptic currents (mEPSCs) increase, a form of plasticity termed "homeostatic synaptic plasticity." We previously showed that a presynaptic protein, the small GTPase Rab3A, is required for full expression of the increase in miniature endplate current amplitudes following prolonged blockade of action potential activity at the mouse neuromuscular junction in vivo (Wang et al., 2011), but it is unknown whether this form of Rab3A-dependent homeostatic plasticity shares any characteristics with central synapses. We show here that homeostatic synaptic plasticity of mEPSCs is impaired in mouse cortical neuron cultures prepared from Rab3A-/- and mutant mice expressing a single point mutation of Rab3A, Rab3A Earlybird mice. To determine if Rab3A is involved in the well-established homeostatic increase in postsynaptic AMPA-type receptors (AMPARs), we performed a series of experiments in which electrophysiological recordings of mEPSCs and confocal imaging of synaptic AMPAR immunofluorescence were assessed within the same cultures. We found that Rab3A was required for the increase in synaptic AMPARs following prolonged activity blockade, but the increase in mEPSC amplitudes was not always accompanied by an increase in postsynaptic AMPAR levels, suggesting other factors may contribute. Finally, we demonstrate that Rab3A is acting in neurons because only selective loss of Rab3A in neurons, not glia, disrupted the homeostatic increase in mEPSC amplitudes. This is the first demonstration that neuronal Rab3A is required for homeostatic synaptic plasticity and that it does so partially through regulation of the surface expression of AMPA receptors.

Blockade of the interleukin-6 signaling pathway in rheumatoid arthritis: Effects on obesity, adipocytokines and glucose metabolism

Interleukin (IL) 6 is one of the key cytokines whose role in the inflammation development in rheumatoid arthritis (RA), is well proven. The pleiotropic effects of the cytokine and biologic agents that inhibit its action have been studied much worse. The review provides information on the effects of IL-6 and blocking its signaling pathway on adipose tissue, glucose metabolism and adipocytokine levels in RA. It has been shown that prolonged blockade of IL-6 receptors does not lead to the adipose tissue accumulation and improves glycemic control, although it is not clear whether such effect is associated only with the anti-inflammatory properties of tocilizumab and sarilumab. Moreover, the mechanism of this beneficial effect is not fully understood, since the data on increased sensitivity of peripheral tissues to insulin during tocilizumab treatment are ambiguous. Perhaps changes in the relationship of adipocytokines or hormones play a certain role.

Combined blockade of mTOR and p21-activated kinases pathways prevents tumour growth in KRAS-mutated colorectal cancer.

The identification of novel therapeutic strategies for metastatic colorectal cancer (mCRC) patients harbouring KRAS mutations represents an unmet clinical need. In this study, we aimed to clarify the role of p21-activated kinases (Paks) as therapeutic target forKRAS-mutated CRC. Paks expression and activation levels were evaluated in a cohort of KRAS-WT or -mutated CRC patients by immunohistochemistry. The effects of Paks inhibition on tumour cell proliferation and signal transduction were assayed by RNAi and by the use of three pan-Paks inhibitors (PF-3758309, FRAX1036, GNE-2861), evaluating CRC cells, spheroids and tumour xenografts' growth. Paks activation positively correlated withKRASmutational status in both patients and cell lines. Moreover, genetic modulation or pharmacological inhibition of Paks led to a robust impairment of KRAS-mut CRC cell proliferation. However, Paks prolonged blockade induced a rapid tumour adaptation through the hyper-activation of the mTOR/p70S6K pathway. The addition of everolimus (mTOR inhibitor) prevented the growth ofKRAS-mut CRC tumoursin vitro and in vivo,reverting the adaptive tumour resistance to Paks targeting. In conclusion, our results suggest the simultaneous blockade of mTOR and Pak pathways as a promising alternative therapeutic strategy for patients affected byKRAS-mut colorectal cancer.

An extended brachial plexus blockade with an original method of catheter fixation: clinical case

BACKGROUND: For extended blockade of the brachial plexus from the supraclavicular access, the catheter is fixed in the supraclavicular region. Owing to the anatomical features of the supraclavicular fossa and the short inner part of the catheter, this fixation method cannot be fully considered reliable and convenient both for the personnel operating the catheter and the patient. The most convenient place for fixing the catheter is the infraclavicular region because of its flat surface. If a catheter is installed to the brachial plexus from the supraclavicular access and the catheter is passed under the skin in the infraclavicular region, then the catheter exit site on the skin will be located further from the surgical intervention area and the inner part of the catheter will be larger.
 CLINICAL CASE DESCRIPTION: This study describes a clinical case of blockade of the brachial plexus by interscalene access with catheterization for prolonged analgesia via supraclavicular access and fixation of the catheter under the skin in the subclavian region in an older patient with polymorbidity during surgical treatment of a closed fracture of the middle third of the humerus. In anesthetic provision, when inducing brachial plexus blockade via a supraclavicular approach, the catheter was fixed in the subcutaneous tunnel of the infraclavicular region for prolonged blockade of the brachial plexus.
 CONCLUSION: This fixation method prevented internal and external dislocation of the catheter, which contributed to high-quality and long-term postoperative analgesia, early patient activity, and absence of infectious complications and created comfortable conditions for the handling of the catheter for both the medical staff and the patient.

Effects of chronic combined treatment with ketanserin and fluoxetine in B6.CBA-D13Mit76C recombinant mice with abnormal 5-НТ<sub>1a</sub> receptor functional activity

The recombinant B6.CBA-D13Mit76C mouse strain is characterized by altered sensitivity of 5-HT1A receptors and greater Htr1a gene transcription. Recently, we found that in B6.CBA-D13Mit76C mice, chronic fluoxetine treatment produced pro-depressive effect in a forced swim test. Since 5-HT2A receptor blockade may be beneficial in treatment-resistant depression, we investigated the influence of chronic treatment (14 days, intraperitoneally) with selective 5-HT2A antagonist ketanserin (0.5 mg/kg), fluoxetine (20 mg/kg), or fluoxetine + ketanserin on the behavior, functional activity of 5-HT1A and 5-HT2A receptors, serotonin turnover, and transcription of principal genes of the serotonin system in the brain of B6.CBA-D13Mit76C mice. Ketanserin did not reverse the pro-depressive effect of fluoxetine. Fluoxetine, ketanserin, and fluoxetine + ketanserin decreased functional activity of 5-HT1A receptors and Htr1a gene transcription in the midbrain and hippocampus. Additionally, all the tested drug regimens decreased mRNA levels of Slc6a4 and Maoa in the midbrain. These changes were not accompanied by a significant shift in the levels of serotonin and its metabolite 5-HIAA. Notably, ketanserin upregulated enzymatic activity of tryptophan hydroxylase 2 (TPH2). Thus, despite some benefits (reduced Htr1a, Slc6a4, and Maoa transcription and increased TPH2 activity), prolonged blockade of 5-HT2A receptors failed to ameliorate the adverse effect of fluoxetine during abnormal functioning of 5-HT1A receptors.

Effects of Chronic Combined Treatment with Ketanserin and Fluoxetine in B6.CBA-D13Mit76C Recombinant Mice with Abnormal 5-HT1A Receptor Functional Activity.

The recombinant B6.CBA-D13Mit76C mouse strain is characterized by an altered sensitivity of 5-HT1A receptors and upregulated 5-HT1A gene transcription. Recently, we found that in B6.CBA-D13Mit76C mice, chronic fluoxetine treatment produced the pro-depressive effect in a forced swim test. Since 5-HT2A receptor blockade may be beneficial in treatment-resistant depression, we investigated the influence of chronic treatment (14 days, intraperitoneally) with selective 5-HT2A antagonist ketanserin (0.5 mg/kg), fluoxetine (20 mg/kg), or fluoxetine + ketanserin on the behavior, functional activity of 5-HT1A and 5-HT2A receptors, serotonin turnover, and transcription of principal genes of the serotonin system in the brain of B6.CBA-D13Mit76C mice. Ketanserin did not reverse the pro-depressive effect of fluoxetine, while fluoxetine, ketanserin, and fluoxetine + ketanserin decreased the functional activity of 5-HT1A receptors and Htr1a gene transcription in the midbrain and hippocampus. All tested drug regimens decreased the mRNA levels of Slc6a4 and Maoa in the midbrain. These changes were not accompanied by a significant shift in the levels of serotonin and its metabolite 5-HIAA. Notably, ketanserin upregulated enzymatic activity of tryptophan hydroxylase 2 (TPH2). Thus, despite some benefits (reduced Htr1a, Slc6a4, and Maoa transcription and increased TPH2 activity), prolonged blockade of 5-HT2A receptors failed to ameliorate the adverse effect of fluoxetine in the case of abnormal functioning of 5-HT1A receptors.

Anticoagulant therapy in a hemodialysis patient at high risk of thrombotic and hemorrhagic complications. Case report

An attempt to preserve the knee joint in a patient on hemodialysis with stage IV lower limb ischemia with a high risk of thrombotic and hemorrhagic complications is presented. Multifocal atherosclerosis and extensive occlusion of the arteries of the lower leg ruled out the technical possibility of revascularization. The patient refused the proposed hip amputation. An attempt was made to perform amputation at the level of the lower leg. Required therapy aimed at the treatment and prevention of thrombotic complications, and optimization of microcirculation in the ischemic limb. For this purpose, a prolonged blockade of the sciatic and femoral nerves, combined anticoagulant therapy, and treatment with alprostadil were performed. Therapy with antithrombotic and vasoactive drugs was not effective and was complicated by the state of persistent hypocoagulation with an episode of bleeding. Amputation of the limb at the level of the thigh was performed according to vital indications after correction of hypocoagulation. The lack of clinical recommendations on anticoagulant therapy for critical lower limb ischemia in patients with stage 5 chronic kidney disease requires an individual approach to the choice of antithrombotic drugs and their doses, monitoring the state of blood coagulation using an integral method for assessing the hemostasis system thromboelastography.

Prolonged blockade of the sciatic nerve in the treatment of pain in patients with chronic limb-threatening ischemia: prospective longitudinal clinical study

BACKGROUND: Systemic multimodal analgesia does not always relieve ischemic pain, and the side effects of its components may be intolerable in patients with comorbid and physically debilitation with chronic limb-threatening ischemia (CLTI). An alternative effective and safe method of pain relief for patients with CLTI is needed.
 OBJECTIVE: To evaluate the efficacy and safety of prolonged popliteal sciatic nerve block in patients with CLTI at the stages of treatment.
 MATERIALS AND METHODS: A prospective clinical study was performed in 31 patients with CLTI. Pain intensity was assessed by a numerical rating scale at the stages of treatment: (1) on admission, (2) presence of systemic multimodal analgesia (paracetamol, ketoprofen, tramadol, and morphine), (3) after catheter insertion to the popliteal sciatic nerve and prolonged nerve block with 0.5% ropivacaine solution, (4) after revascularization without anesthesia, (5) after revascularization in the presence of nerve blockade, and (6) upon discharge. Catheter insertion was performed under ultrasound control and neurostimulation. Pain intensity, frequency of insomnia, and forced lowering of the limb, need for narcotic analgesics, and patient satisfaction with treatment were assessed.
 RESULTS: Regional block before surgery provided better pain relief than systemic multimodal analgesia (p 0.001) and reduced the need for narcotic analgesics (p 0.001). Insomnia was observed less frequently with prolonged blockade of the sciatic nerve than with systemic multimodal analgesia (p 0.05), as well as forced lowering of the limb (p 0.05). Revascularization of the lower extremity has an analgesic effect; however, pain relief is required for most patients. Pain relief through sciatic nerve block at all stages of CLTI treatment, sleep normalization, and freedom from forced posture improved the quality of life and satisfaction with treatment. No complications associated with the regional blockade were recorded.
 CONCLUSION: Prolonged popliteal sciatic nerve block effectively relieves pain in patients with CLTI, is safe, and can be an alternative to systemic anesthesia.

Homeostatic regulation of extracellular signal-regulated kinase 1/2 activity and axonal Kv7.3 expression by prolonged blockade of hippocampal neuronal activity.

Homeostatic plasticity encompasses the mechanisms by which neurons stabilize their synaptic strength and excitability in response to prolonged and destabilizing changes in their network activity. Prolonged activity blockade leads to homeostatic scaling of action potential (AP) firing rate in hippocampal neurons in part by decreased activity of N-Methyl-D-Aspartate receptors and subsequent transcriptional down-regulation of potassium channel genes including KCNQ3 which encodes Kv7.3. Neuronal Kv7 channels are mostly heterotetramers of Kv7.2 and Kv7.3 subunits and are highly enriched at the axon initial segment (AIS) where their current potently inhibits repetitive and burst firing of APs. However, whether a decrease in Kv7.3 expression occurs at the AIS during homeostatic scaling of intrinsic excitability and what signaling pathway reduces KCNQ3 transcript upon prolonged activity blockade remain unknown. Here, we report that prolonged activity blockade in cultured hippocampal neurons reduces the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) followed by a decrease in the activation of brain-derived neurotrophic factor (BDNF) receptor, Tropomyosin receptor kinase B (TrkB). Furthermore, both prolonged activity blockade and prolonged pharmacological inhibition of ERK1/2 decrease KCNQ3 and BDNF transcripts as well as the density of Kv7.3 and ankyrin-G at the AIS. Collectively, our findings suggest that a reduction in the ERK1/2 activity and subsequent transcriptional down-regulation may serve as a potential signaling pathway that links prolonged activity blockade to homeostatic control of BDNF-TrkB signaling and Kv7.3 density at the AIS during homeostatic scaling of AP firing rate.

Bilateral Sphenopalatine Ganglion Block With Liposomal Bupivacaine Followed by Severe Hypertension: A Case Report

We reviewed a case of bilateral sphenopalatine ganglion (SPG) blockade with liposomal bupivacaine for sinus surgery. The case was complicated by severe postoperative hypertension refractory to antihypertensives and needing intensive care unit (ICU) admission. While SPG blockade has been used to treat headaches and provide perioperative analgesia, this complication and a possible mechanism have not been described. We discuss how local anesthetic spread beyond the SPG may have caused prolonged parasympathetic blockade and hypertension. Before approved indications are established, we recommend avoiding the use of liposomal bupivacaine in off-label settings when the function of bilateral autonomic structures could be affected.

Системна запальна відповідь після операцій на кульшовому суглобі: порівняння спінальної анестезії та комбінації спінальної анестезії з паравертебральною блокадою

Актуальність. C-реактивний білок (CRP) як біохімічний маркер неспецифічного запалення є об’єктивною мірою інвазивності при протезуванні кульшового суглоба. Мета дослідження. Порівняння рівнів CRP після операцій на кульшовому суглобі в умовах або комбінації спінальної анестезії з паравертебральною блокадою, або однієї лише спінальної анестезії. Матеріали та методи. 22 пацієнти, які мали однобічні операції на кульшовому суглобі, були випадковим чином розподілені на дві групи. У контрольній групі (n = 11) проводилась одноразова спінальна анестезія. У дослідній групі (n = 11) під час операції застосовувалась така сама спінальна анестезія, а після операції — однобічна пролонгована паравертебральна блокада. Результати. У 1, 3 і 7-й післяопераційні дні рівні CRP були статистично значуще (p < 0,05) нижчими у дослідній групі, ніж у контрольній. Висновки. Післяопераційне знеболювання пролонгованою паравертебральною блокадою після інтраопераційної спінальної анестезії для операцій на кульшовому суглобі супроводжується меншим зростанням рівня CRP, ніж після однієї лише спінальної анестезії.

Пролонгована паравертебральна аналгезія для знеболювання у хворих після торакотомії

Актуальність. Торакотомія відноситься до одного з найбільш травматичних втручань в хірургії, що супроводжується вираженим гострим болем після операції та розвитком хронічного больового синдрому у віддаленому післяопераційному періоді. Мета дослідження. Порівняти ефективність та безпечність різних методів знеболювання хворих після торакотомії. Матеріали та методи. Після торакотомії 85 хворих було розподілено на три дослідні групи. Знеболювання проводили за допомогою пролонгованої паравертебральної аналгезії (ПВА) (19 хворих) і пролонгованої епідуральної аналгезії (ЕДА) (36 хворих) 0,2% розчином ропівакаїну зі швидкістю 6 мл/год (у паравертебральний або епідуральний простір). У контрольній групі (30 хворих) знеболювання проводилось внутрішньовенною, контрольованою пацієнтом аналгезією розчином морфіну. Як ад’ювантний анальгетик у всіх трьох дослідних групах використовували нестероїдний протизапальний препарат кеторолаку трометамін внутрішньом’язово. У ранньому післяопераційному періоді оцінювали рівень болю в стані спокою та під час фізичного навантаження дихальної мускулатури (виконання спірометрії), показники функції зовнішнього дихання (ФЗД), а також частоту та тип ускладнень застосованих методів знеболювання. У віддаленому післяопераційному періоді оцінювали частоту виникнення хронічного болю. Результати. У групах з пролонгованою ПВА і ЕДА інтенсивність больового синдрому протягом трьох діб післяопераційного періоду за візуальною аналоговою шкалою (ВАШ) у стані спокою була меншою порівняно з контрольною групою. У групі ПВА рівень болю був від 29,1 бала через чотири години після операції до 18,7 бала в кінці третьої доби; у групі ЕДА — від 24,2 до 20,3 бала відповідно; у контрольній групі — від 48,8 до 38,0 бала відповідно. Під час дослідження ФЗД інтенсивність болю в групах ПВА і ЕДА також була нижчою порівняно з контрольною групою і становила 33,8 бала в групі ПВА, 38,7 бала — в групі ЕДА, 61,2 — у контрольній групі. Частоту виникнення хронічного больового синдрому оцінювали через 6 місяців після операції. Було відібрано по 15 хворих із кожної групи. У контрольній групі хронічний больовий синдром розвинувся у 8 хворих (53 %), у групі ЕДА — у 5 хворих (33,3 %), у групі ПВА — у 3 хворих (20 %). Найменша кількість ускладнень і технічних невдач спостерігалась у групі ПВА. Висновки. У групі з пролонгованою ПВА порівняно з пролонгованою ЕДА рівень болю за ВАШ був нижчим, частота випадків хронічного болю меншою, а кількість побічних ефектів мінімальною. Пролонгована паравертебральна блокада у хворих після торакотомії дає змогу ефективно контролювати гострий післяопераційний біль та зменшує розвиток хронічного больового синдрому.

The Assessment of Prolonged Inferior Alveolar Nerve Blockade for Postoperative Analgesia in Mandibular Third Molar Surgery by a Perineural Addition of Dexamethasone to 0.5% Ropivacaine: A Randomized Comparison Study

Background: Perineurally adding dexamethasone to local anesthetics could enable postoperative analgesia. Our aim was to investigate the efficacy of 4 mg dexamethasone and 0.5% ropivacaine on the prolonged duration of mandibular anesthesia for postoperative analgesia during third molar surgery. Materials and method: The patients of both sexes, and in the age range of 17 to 50 yrs of age, received the Gow-Gates anesthesia. Group I received 4 mL of plain 0.5% ropivacaine, with perineurally added 1 mL/4 mg of dexamethasone; group II received 4 mL of plain 0.5% ropivacaine with perineurally added 1 mL of 0.9% saline; group III received 4 mL of plain 0.5 bupivacaine with perineurally added 1 mL of 0.9% saline. The prime anesthesia outcome was the duration of conduction anesthesia (DCA); the secondary outcome was the duration of analgesia (DAN) and analgesia before analgesic intake. Results: In 45 randomly selected subjects (mean age 27.06 ± 8.20), DCA was statistically longest in group I (n = 15) (592.50 ± 161.75 min, p = 0.001), collated with groups II (n = 15) and III (n = 15) (307.40 ± 84.71 and 367.07 ± 170.52 min, respectively). DAN was significantly the longest in group I (mean: 654.9 ± 198.4 min, p = 0.001), compared with group II (345.4 ± 88.0 min) and group III (413.7 ± 152.3 min), with insignificant adverse reactions. One-third of the operated patients absented from the use of analgesics. Conclusion: A amount 0.5% ropivacaine with dexamethasone usefully served as an analgesic with a success rate of 93.4% of the given anesthesia.

Abstract IA07: Impact of immunotherapy on COVID-19 immunity: Insights from checkpoint blockade in cancer

Abstract Over the last few years, we have gained insights into how immunotherapy, including checkpoint blockade, modulates key CD4 and CD8 T cell subsets in anti-tumor immunity. This information can now give us insights into how immunotherapy can impact immunity in the setting of COVID-19. Indeed, we recently demonstrated that cancer patients with T cell depletion have high COVID-19 mortality despite adequate B cell and antibody production, highlighting the importance of cellular immunity. Conversely, in the setting of B cell depletion by anti-CD20 therapy, CD8 T cells can compensate for impaired humoral immunity. PD-1 blockade increases the activation and proliferation of CD4 T follicular-helper cells, which plays a key role in promoting B cell responses and quality antibody production. Thus, it is possible that PD-1 blockade enhances the efficacy of SARS-CoV-2 vaccination. However, PD-1 blockade in melanoma patients was actually associated with at 2-fold decrease in SARS-CoV-2 specific antibodies and neutralizing antibodies, compared to a healthy donor cohort. PD-1 blockade was also associated with depletion of memory CD4 T cells, suggesting there may be consequences to prolonged PD-1 blockade. Citation Format: Paulina Coutifaris, Kevin Wang, Sokratis Apostolidis, Mark Painter, Ahron Flowers, Rishi Goel, Divij Mathew, Ajinkya Pattekar, Ravi Amaravadi, Tara Mitchell, Paul Bates, Scott Hensley, Giorgos Karakousis, Lynn Schuchter, Allie Greenplate, E. John Wherry, Alexander C. Huang. Impact of immunotherapy on COVID-19 immunity: Insights from checkpoint blockade in cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr IA07.

Prolonged blockade of the cervical sympathetic nerve by stellate ganglion block accelerates therapeutic efficacy in trigeminal neuropathy

Stellate ganglion block (SGB) is effective in treating head and neck pain and neuropathic diseases by increasing tissue blood flow through its sympatholytic effect. This study aimed to investigate the relationship between duration of cervical sympathetic nerve block by SGB and its therapeutic efficacy against trigeminal neuropathy after orthognathic surgery. Twenty-eight patients with trigeminal neuropathy were randomly assigned to two groups (mepivacaine and levobupivacaine) according to the drug used for SGB. Increased blood flow, which is a symptom of sympathetic blockade, was recorded for 180 min after SGB. Current perception threshold, warm or cool detection threshold, and tactile detection threshold were measured preoperatively, postoperatively, on day 10 after initiation of SGB, and 3 months postoperatively to compare therapeutic efficacy between the groups. The levobupivacaine group had a significantly longer duration of increased blood flow compared with the mepivacaine group. Values of current perception threshold, warm and cool detection threshold, and tactile detection threshold significantly improved in the levobupivacaine group on day 10 after initiation of SGB and 3 months postoperatively. A prolonged increase in blood flow due to long-term sympatholytic effects accelerates the therapeutic efficacy of SGB in trigeminal neuropathy.

Influence of Catheter–Incision Congruency in Epidural Analgesia on Postcesarean Pain Management: A Single-Blinded Randomized Controlled Trial

Patient-controlled epidural analgesia (PCEA) or epidural morphine may alleviate postcesarean pain; however, conventional lumbar epidural insertion is catheter–incision incongruent for cesarean delivery. Methods: In total, 189 women who underwent cesarean delivery were randomly divided into four groups (low thoracic PCEA, lumbar PCEA, low thoracic morphine, and lumbar morphine groups) for postcesarean pain management. Pain intensities, including static pain, dynamic pain, and uterine cramp, were measured using a 100 mm visual analog scale (VAS). The proportion of participants who experienced dynamic wound pain with a VAS score of >33 mm was evaluated as the primary outcome. Adverse effects, including lower extremity blockade, pruritus, postoperative nausea and vomiting, sedation, and time of first passage of flatulence, were evaluated. Results: The low thoracic PCEA group had the lowest proportion of participants reporting dynamic pain at 6 h after spinal anesthesia (low thoracic PCEA, 28.8%; lumbar PCEA, 69.4%; low thoracic morphine, 67.3%; lumbar morphine group, 73.9%; p < 0.001). The aforementioned group also reported the most favorable VAS scores for static, dynamic, and uterine cramp pain during the first 24 h after surgery. Adverse effect profiles were similar among the four groups, but a higher proportion of participants in the lumbar PCEA group (approximately 20% more than in the other three groups) reported prolonged postoperative lower extremity motor blockade (p = 0.005). In addition, the first passage of flatulence after surgery reported by the low thoracic PCEA group was approximately 8 h earlier than that of the two morphine groups (p < 0.001). Conclusions: Epidural congruency is essential to PCEA for postcesarean pain. Low thoracic PCEA achieves favorable analgesic effects and may promote postoperative gastrointestinal recovery without additional adverse effects.

Prolonged neuromuscular block after rocuronium administration in laparoscopic pyloromyotomy patients: A retrospective bayesian regression analysis.

Infants undergoing pyloromyotomy are at a high risk of aspiration, making rapid sequence induction the preferred method of induction. Since succinylcholine use in infants can be associated with complications, rocuronium is frequently substituted despite its prolonged duration of action. To examine the likelihood of non-reversibility to neostigmine at the end of surgery in laparoscopic pyloromyotomies and its correlation to both rocuronium dose and out of operating room time. Patients who underwent laparoscopic pyloromyotomy for infantile hypertrophic pyloric stenosis, received rocuronium, and were reversed with neostigmine were included. Bayesian multivariable logistic regression was utilized to determine the probability of non-reversibility, and Bayesian multivariable median regression was performed to ascertain the correlation between out of operating room time and non-reversibility. 306 patients were analyzed with a median surgical duration of 19min (interquartile range 16 to 23). 74% received succinylcholine for intubation followed by rocuronium, and the remaining received rocuronium alone. The median rocuronium dose was 0.41mg/kg (interquartile range 0.27 - 0.56mg/kg). Prolonged block occurred in 68 (22.2%) patients. There was a non-trivial probability of prolonged block with low rocuronium doses, and each 0.1mg/kg increase in total rocuronium dose was associated with an odds ratio of 1.36 (95% credible interval: 1.17-1.58) of neostigmine non-reversibility at the end of surgery. Non-reversibility was correlated with a substantial increase in median out of operating room time (13.4min, 95% credible interval: 5.5-20.8min), which was compounded by high rocuronium dosing (2.2min increase per 0.1mg/kg for doses greater than 0.5mg/kg, 95% credible interval: 0.7-3.6min). Prolonged blockade can occur from rocuronium administration in infants undergoing pyloromyotomy even at low doses. Therefore, consideration of appropriate rocuronium dosing or the use of sugammadex should be considered.

Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury.

Cerebrovascular injuries can cause severe edema and inflammation that adversely affect human health. Here, we observed recanalization after successful endovascular thrombectomy for acute large vessel occlusion was associated with cerebral edema and poor clinical outcomes in patients who experienced hemorrhagic transformation. To understand this process, we developed a cerebrovascular injury model using transcranial ultrasound that enabled spatiotemporal evaluation of resident and peripheral myeloid cells. We discovered that injurious and reparative responses diverged based on time and cellular origin. Resident microglia initially stabilized damaged vessels in a purinergic receptor-dependent manner, which was followed by influx of myelomonocytic cells that caused severe edema. Prolonged blockade of myeloid cell recruitment with anti-adhesion molecule therapy prevented severe edema but also promoted neuronal destruction and fibrosis by interfering with vascular repair later orchestrated by pro-inflammatory monocytes and pro-angiogenic repair-associated microglia (RAM). These data demonstrate how temporally distinct myeloid cell responses can contain, exacerbate, and ultimately repair a cerebrovascular injury.

Dynamics of perioperative changes in hemostatic potential according to low-frequency piezoelectric thromboelastography data in open transvesical prostatectomy under epidural analgesia

Background. The anesthetic technique of choice for urological surgeries is a controversial issue, especially for transvesical prostatectomy for patients with benign prostatic hyperplasia (BPH). Often, epidural anesthesia and analgesia are considered as the methods of choice. However, the effect of an anesthetic support on perioperative changes in hemostatic potential has been poorly studied.&#x0D; Aim. The aim of the study was to demonstrate the dynamics of changes in the system of the aggregate blood state regulation by using an instrumental method, a low-frequency piezoelectric thromboelastography (LFPTEG), in the perioperative period for patients with BPH who will undergo transvesical prostatectomy.&#x0D; Material and methods. The state of the hemostatic system in a group of 71 patients with confirmed BPH who required a transvesical prostatectomy was evaluated by the APC ARP-01M Mednord device at the time of the admission, 30 min after the effect of an epidural anesthesia, an hour after the end of a surgery and a day after a surgery.&#x0D; Results. A perioperative dynamic monitoring of the state of a hemostatic balance showed that a preoperative hypercoagulation, compensated by an increased fibrinolysis, was replaced by a normocoagulation at the moment of a surgery, which was observed in the first hour after the end of a surgery and retained until the end of the first day.&#x0D; Conclusion. Hypercoagulation was found out for patients with BPH before a transvesical prostatectomy that was masked by an activation of the fibrinolytic system. The hemostatic potential assumed values identical to the reference values that should be taken into account prescribing a postoperative thromboprophylaxis against the background of a prolonged epidural blockade. The APC ARP-01M Mednord device allows you to assess all parts of a hemocoagulation at each stage of a perioperative treatment quickly and without high material costs.