Lidocaine induces epithelial­mesenchymal transition and aggravates cancer behaviors in non­small cell lung cancer A549 cells.

The effects of clinically relevant concentrations of lidocaine on epithelial-mesenchymal transition (EMT) and associated lung cancer behaviors have rarely been investigated. The aim of the present study was to assess the impact of lidocaine on EMT and its related phenomena, including chemoresistance. Lung cancer cell lines (A549 and LLC.LG) were incubated with various concentrations of lidocaine, 5-fluorouracil (5-FU) or both to test their effects on cell viability. Subsequently, the effects of lidocaine on various cell behaviors were assessed in vitro and in vivo using Transwell migration, colony-formation and anoikis-resistant cell aggregation assays, and human tumor cell metastasis in a chorioallantoic membrane (CAM) model quantitated by PCR analysis. Prototypical EMT markers and their molecular switch were analyzed using western blotting. In addition, a conditioned metastasis pathway was generated through Ingenuity Pathway Analysis. Based on these measured proteins (slug, vimentin and E-cadherin), the molecules involved and the alteration of genes associated with metastasis were predicted. Of note, clinically relevant concentrations of lidocaine did not affect lung cancer cell viability or alter the effects of 5-FU on cell survival; however, at this dose range, lidocaine attenuated the 5-FU-induced inhibitory effect on cell migration and promoted EMT. The expression levels of vimentin and Slug were upregulated, whereas the expression of E-cadherin was downregulated. EMT-associated anoikis resistance was also induced by lidocaine administration. In addition, portions of the lower CAM with a dense distribution of blood vessels exhibited markedly increased Alu expression 24 h following the inoculation of lidocaine-treated A549 cells on the upper CAM. Thus, at clinically relevant concentrations, lidocaine has the potential to aggravate cancer behaviors in non-small cell lung cancer cells. The phenomena accompanying lidocaine-aggravated migration and metastasis included altered prototypical EMT markers, anoikis-resistant cell aggregation and attenuation of the 5-FU-induced inhibitory effect on cell migration.

Onset Time of Lumbar Erector Spinae Plane Block Compared with Its Thoracic Counterpart: Case Reports.

The erector spinae plane block (ESPB) at the level of the fifth thoracic vertebra (T5) is a novel technique, first published in 2016, which was found to be effective in both acute and chronic pain control. The mechanism of action and spread of local anesthetic of the ESPB at the lumbar region are thought to differ from those of the thoracic ESPB; however, the difference in onset time has never been evaluated. As for the onset of lumbar ESPBs, we presented three cases: two received lumbar ESPBs (one with chronic low back pain and one with acute postoperative hip pain), and the third one with chronic back pain received a thoracic ESPB. We administered 30 mL of 0.3% ropivacaine in all three patients, but the analgesic effect did not reach its maximum until 3 and 1.5 h, respectively, in the lumbar ESPB cases. On the contrary, the thoracic ESPB case experienced noticeable pain relief within 30 min. The onset time was considerably longer than that reported in earlier reports on ESPBs, and the lumbar ESPB achieved its peak effect much later than the thoracic ESPB using the same formula of local anesthetic. While the delayed-onset lumbar ESPB may have some drawbacks for treating acute postoperative pain, it still could produce significant analgesia, once it took effect, when given to patients suffering from hip surgery with large incisions and intractable low back pain. The current data suggested that the onset time of a lumbar ESPB may be delayed compared with its thoracic counterpart. Therefore, the local anesthetic formula and injection timing should be adjusted for a lumbar ESPB when applied in the perioperative period to make the onset of the analgesic effect coincide with the immediate postoperative pain. Without this concept in mind, clinicians may consider a lumbar ESPB to be ineffective before it takes effect, and consequently treat the patients inadequately with this technique. Future randomized controlled trials should be designed according to our observations to compare lumbar ESPB with its thoracic counterpart regarding onset time.

Motor-Sparing Effect of Adductor Canal Block for Knee Analgesia: An Updated Review and a Subgroup Analysis of Randomized Controlled Trials Based on a Corrected Classification System.

OBJECTIVE: Discrepancies in the definition of adductor canal block (ACB) lead to inconsistent results. To investigate the actual analgesic and motor-sparing effects of ACB by anatomically defining femoral triangle block (FTB), proximal ACB (p-ACB), and distal ACB (d-ACB), we re-classified the previously claimed ACB approaches according to the ultrasound findings or descriptions in the corresponding published articles. A meta-analysis with subsequent subgroup analyses based on these corrected results was performed to examine the true impact of ACB on its analgesic effect and motor function (quadriceps muscle strength or mobilization ability). An optimal ACB technique was also suggested based on an updated review of evidence and ultrasound anatomy. MATERIALS AND METHODS: We systematically searched studies describing the use of ACB for knee surgery. Cochrane Library, PubMed, Web of Science, and Embase were searched with the exclusion of non-English articles from inception to 28 February 2022. The motor-sparing and analgesic aspects in true ACB were evaluated using meta-analyses with subsequent subgroup analyses according to the corrected classification system. RESULTS: The meta-analysis includes 19 randomized controlled trials. Compared with the femoral nerve block group, the quadriceps muscle strength (standardized mean difference (SMD) = 0.33, 95%-CI [0.01; 0.65]) and mobilization ability (SMD = -22.44, 95%-CI [-35.37; -9.51]) are more preserved in the mixed ACB group at 24 h after knee surgery. Compared with the true ACB group, the FTB group (SMD = 5.59, 95%-CI [3.44; 8.46]) has a significantly decreased mobilization ability at 24 h after knee surgery. CONCLUSION: By using the corrected classification system, we proved the motor-sparing effect of true ACB compared to FTB. According to the updated ultrasound anatomy, we suggested proximal ACB to be the analgesic technique of choice for knee surgery. Although a single-shot ACB is limited in duration, it remains the candidate of the analgesic standard for knee surgery on postoperative day 1 or 2 because it induces analgesia with less motor involvement in the era of multimodal analgesia. Furthermore, data from the corrected classification system may provide the basis for future research.

Bidirectional Irrigation System to Treat a Difficult Wound: A Case Series.

AIMS: To date, there is no distinct principle determining whether to use irrigation under negative-pressure wound therapy (NPWT). We developed a new economical device to manage difficult wounds, employing 1 of 2 techniques depending on the wound condition. METHODS: This case series study was conducted in 12 patients with difficult wound, from 2017 to 2018. Four patients were treated with Type A bidirectional irrigation system (wound irrigation), while 8 patients were treated with Type B bidirectional irrigation system (wound irrigation combined with NPWT). RESULTS: In the Type A device group, inflammatory profiles in case I, case IV, and case VIII were not monitored due to the stability of their wound. The mean recovery period was 3.75 weeks (2-8 weeks), with decreases in 100% healing rate. In the Type B device group, we noted an average of 71% reduction in inflammatory profiles. All patients' infections were resolved or were healing, and 7 patients recovered satisfactorily. The recovery period ranged from 4 to 17 weeks, with a median value of 7 weeks. CONCLUSION: Bidirectional irrigation system decreases secondary infections and complications, and increases the healing rate in patients with difficult wound.

Prospective Observational Study after Eversion Carotid Endarterectomy with Ultrasound-Guided Deep-Intermediate Cervical Plexus Blockade.

(1) Introduction: The aim was to describe the anesthetic and surgical technique of eversion carotid endarterectomy performed under intermediate-deep cervical block with sedation, and to analyze the intraoperative and postoperative results. (2) Material and Methods: Thirty cases of unilateral eversion carotid endarterectomy (n = 30), performed between 2019-2020 in a tertiary center under intermediate-deep ultrasound-guided cervical plexus block and sedation, were prospectively observed and analyzed. Hemodynamic (blood pressure, heart rate) and neurological (cerebral oximetry) variables were measured in four intraoperative phases: at the beginning of the operation, prior to carotid clamping, after unclamping and at the end of the operation. We assessed acute postoperative pain in a numerical rating scale at 6, 12 and 24 h, early and 30-day complications, and length of stay. (3) Results: Baseline mean arterial pressure values were 100.4 ± 18 mmHg, pre-clamping 95.8 ± 14 mmHg, post-clamping 94.9 ± 11 mmHg, and at the end of the operation 102.4 ± 16 mmHg. Cerebral oximetry values were 61.7 ± 7/62.7 ± 8, 68.5 ± 9.6/69.1 ± 11.7 and 68.1 ± 10/68.1 ± 10 for the left and right hemispheres at baseline, pre- and post-clamping, respectively. The pain assessment showed a score less than or equal to 3. The incidence of residual nerve block, early complications, and major complications in the first 30 days was 40%, 16.7% and 3.3%, respectively. (4) Conclusions: The combination of intermediate-deep cervical plexus block and low-dose sedation is an effective and safe alternative in awake eversion carotid endarterectomy.

Regional Anesthetic and Analgesic Techniques for Clavicle Fractures and Clavicle Surgeries: Part 2-A Retrospective Study.

Objective. Clavicle fracture fixation is commonly performed under general anesthesia due to the complex sensory innervation in this region which poses a challenge for anesthesiologists applying regional anesthetic (RA) techniques. In part 1 of this two-part study, we summarized the current literature describing various RA approaches in clavicle fractures and surgery. In our earlier scoping review, we surmised that a superficial or intermediate cervical plexus block (CPB) may provide analgesia for this procedure and, when combined with an interscalene brachial plexus block (ISB), can provide anesthesia to the clavicular region for surgical fixation. We performed a retrospective study, consolidating assumptions that were based on the results of our earlier scoping review. Methods. A retrospective study was conducted on 168 consecutive patients who underwent clavicle fixation surgery at a tertiary healthcare system in Singapore. We used a standardized pro forma to collate perioperative data from the electronic health records of both hospitals, including anesthetic technique, analgesic requirements, pain scores, and adverse events, up to the second postoperative day or up until discharge. Results. In our study, patients who received RA had significantly reduced pain scores and opioid requirements, compared to general anesthesia (GA) alone. Through subgroup analysis, differences were found in postoperative pain scores and opioid requirements in the following order: GA alone > GA with local infiltration analgesia > CPB > CPB plus ISB. All patients who received combined CPB and ISB had upper limb weakness in recovery, compared to none with CPB alone (p < 0.001). Of those who received an ISB either in isolation or combined with a CPB, four (9.3%) were reported to have dyspnea (within 24 h) and motor weakness that persisted beyond 12 h, compared to none for patients that received CPB alone. Conclusions. Addition of a CPB to GA for clavicle fracture fixation surgery is associated with reduced pain scores in the early postoperative period, with a lower opioid requirement compared to GA alone. In patients undergoing GA, the combination of a CPB with an ISB was associated with a small, although statistically significant, reduction in pain scores and opioid requirements compared to a CPB alone.

Correction: Yeoh et al. Pericapsular Nerve Group Block and Iliopsoas Plane Block: A Scoping Review of Quadriceps Weakness after Two Proclaimed Motor-Sparing Hip Blocks. Healthcare 2022, 10, 1565.

In the original publication [...].

Regional Anesthetic and Analgesic Techniques for Clavicle Fractures and Clavicle Surgeries: Part 1-A Scoping Review.

Objective. Clavicle fractures are common injuries potentially associated with significant perioperative pain. However, this region's complex sensory innervation poses a challenge for regional anesthetic or analgesic (RA) techniques. We conducted this scoping review to summarize the current literature, particularly with regards to motor-sparing techniques. Methods. A scoping review was carried out in accordance with the Joanna Briggs Institute's framework. All articles describing the use of RA for clavicle fractures or surgery were included. PubMed®, Ovid MEDLINE®, EMBASE®, Scopus®, CINAHL®, and the Cochrane database were searched without language restrictions. Results. Database searches identified 845 articles, 44 of which were included in this review, with a combined patient total of 3161. We included all peer-reviewed publications containing clinical data and summarized the findings. Conclusions. Current evidence of RA techniques in clavicle surgery is heterogeneous, with different approaches used to overcome the overlapping sensory innervation. The literature largely comprises case reports/series, with several randomized controlled trials. Intermediate cervical plexus block is the regional technique of choice for clavicle surgery, and can provide reliable surgical anesthesia when combined with an interscalene block. Cervical plexus block can provide motor-sparing analgesia following clavicle surgery. Promising alternatives include the clavipectoral block, which is a novel motor-sparing regional technique. Further studies are required to determine the efficacy and safety of various techniques.

Pericapsular Nerve Group Block and Iliopsoas Plane Block: A Scoping Review of Quadriceps Weakness after Two Proclaimed Motor-Sparing Hip Blocks.

Iliopsoas plane (IP) is a fascial plane deep to the iliopsoas complex that can serve as a potential space for the injection of local anesthetics to selectively block the articular branches of femoral nerve and accessory obturator nerve to the anterior hip capsule. Two highly similar ultrasound-guided interfascial plane blocks that target the IP, pericapsular nerve group (PENG) block and iliopsoas plane block (IPB), were both designed to achieve motor-sparing sensory block to the anterior hip capsule. However, the most recent evidence shows that PENG block can cause 25% or more of quadriceps weakness, while IPB remains the hip block that can preserve quadriceps strength. In this scoping review of quadriceps weakness after PENG block and IPB, we first performed a focused review on the complicated anatomy surrounding the anterior hip capsule. Then, we systematically searched for all currently available cadaveric and clinical studies utilizing PENG block and IPB, with a focus on quadriceps weakness and its potential mechanism from the perspectives of fascial plane spread along and outside of the IP. We conclude that quadriceps weakness after PENG block, which places its needle tip directly deep to iliopsoas tendon (IT), may be the result of iliopectineal bursal injection. The incidental bursal injection, which can be observed on ultrasound as a medial fascial plane spread, can cause bursal rupture/puncture and an anteromedial extra-IP spread to involve the femoral nerve proper within fascia iliaca compartment (FIC). In comparison, IPB places its needle tip lateral to IT and injects just one-fourth of the volume of PENG block. The current evidence, albeit still limited, supports IPB as the true motor-sparing hip block. To avoid quadriceps weakness after PENG block, a more laterally placed needle tip, away from the undersurface of IT, and a reduction in injection volume should be considered. Future studies should focus on comparing the analgesic effects and quadriceps function impairment between PENG block and IPB.

Effect of Sarcopenia on Mortality in Type 2 Diabetes: A Long-Term Follow-Up Propensity Score-Matched Diabetes Cohort Study.

Purpose: The effect of sarcopenia on the survival of patients with type 2 diabetes remains unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare the patients with diabetes with or without sarcopenia. Patients and Methods: We included patients with type 2 diabetes and categorized them into two groups according to whether they had sarcopenia and compared their survival; patients in the groups were matched at a ratio of 1:2. Results: The matching process yielded a final cohort of 201,698 patients (132,805 and 68,893 in the sarcopenia and nonsarcopenia diabetes groups, respectively) who were eligible for further analysis. According to both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of all-cause death for the sarcopenia diabetes group compared with the control group: 1.35 (1.33−1.38; p < 0.001). The aHRs (95% CIs) of all-cause death for those aged 41−50, 51−60, and >60 years (compared with those aged ≤40 years) were 1.53 (1.48−1.60), 2.61 (2.52−2.72), and 6.21 (5.99−6.45), respectively. The aHR (95% CI) of all-cause death for the male patients compared with the female patients was 1.56 (1.54−1.60). The aHRs (95% CIs) of all-cause death for those with adapted Diabetes Complications Severity Index (aDCSI) scores of 1, 2, 3, 4, and ≥5 (compared with an aDCSI score of 0) were 1.01 (1.00−1.14), 1.38 (1.35−1.42), 1.58 (1.54−1.63), and 2.23 (2.14−2.33), respectively. Conclusion: Patients with type 2 diabetes and sarcopenia had higher mortality than did those without sarcopenia.

Efficacy of Acupuncture, Intravenous Lidocaine, and Diet in the Management of Patients with Fibromyalgia: A Systematic Review and Network Meta-Analysis.

Introduction: This network meta-analysis aimed to assess the efficacy of acupuncture, intravenous lidocaine, and diet compared with other comparators such as physiotherapy and sham/placebo in fibromyalgia patients. Materials and Methods: We searched Embase, PubMed, Scopus, and Web of Science for relevant studies till September 2021. The included studies were randomized controlled clinical trials. For the network meta-analysis, we used the R software. Results: There were 23 included RCTs. The total sample size was 1409 patients. Compared with the sham/placebo group, the network analysis showed the highest improvement in the quality of life in the acupuncture group standardized mean difference (SMD) = -10.28, 95%-CI [-14.96; -5.59]), and then in the physiotherapy group (SMD = -7.48, 95%-CI [-14.72; -0.23]). For the pain, there was a significant reduction with acupuncture (SMD = -1.69, 95%-CI [-2.48; -0.89]), compared with sham/placebo. Regarding depression, it showed a significant reduction with acupuncture (SMD = -9.64, 95%-CI [-16.13; -3.14]) compared with sham/placebo. Finally, for stiffness, it showed no significant differences in the stiffness between acupuncture (SMD = -8.52, 95%-CI [-20.40; 3.36]), fluoxetine (SMD = -6.52, 95%-CI [-29.65; 16.61]), and physiotherapy (SMD = -4.64, 95%-CI [-22.83; 13.54]) compared with sham/placebo. Conclusions: The acupuncture showed a significant effect in the management of fibromyalgia patients. It reduced pain, depression, and enhanced the quality of life. While physiotherapy showed a significant improvement in the quality of life only. In contrast, intravenous lidocaine and diet showed no significant differences when compared with sham/placebo.

Parameters of Iliopsoas Plane Immediately Caudal to the Indirect Tendon of Rectus Femoris in Axial Plane Measured on Magnetic Resonance Images in an Adult Eastern Asian Population.

The iliopsoas plane (IP) is a fascial plane deep to the iliopsoas complex and is the target of several novel ultrasound-guided analgesic interventions for hip. Currently, limited information is known about its parameters. From the pelvic magnetic resonance (MR) images of an adult Eastern Asian population (n = 49), the IP width, depth, and needle-beam angle in the axial plane immediately caudal to the level of indirect tendon of rectus femoris (RF) were found to be 10.7 ± 1.6 mm, 48.5 ± 15.5 mm, and 84.2 ± 8.2 degrees, respectively. There was a statistically significant difference in the age categories for IP width, and older patients seemed to have wider IP. Our data may provide applications for the technical modification of ultrasound-guided iliopsoas plane block (IPB) in acute hip pain management and the future development of ultrasound-guided single-needle-entry radiofrequency neuroablation in chronic hip pain management.

Efficacy of Ultrasound-Guided Injection of Botulinum Toxin, Ozone, and Lidocaine in Piriformis Syndrome.

Background: Piriformis syndrome (PS) is a painful musculoskeletal condition characterized by a deep gluteal pain that may radiate to the posterior thigh and leg. This study was designed to compare the effectiveness of ozone and BTX to lidocaine injection in treating piriformis syndrome that was resistant to medication and/or physical therapy. Study design: Between November 2018 and August 2019, we involved eighty-four subjects diagnosed with piriformis syndrome in a double-blinded, prospective, randomized comparative study to receive an ultrasound-guided injection of lidocaine (control group), botulinum toxin A, or local ozone (28 patients each group) in the belly of the piriformis muscle. Pain condition evaluated by the visual analog score (VAS) was used as a primary outcome, and the Oswestry Disability Index (ODI) as a secondary outcome, before, at one month, two months, three months, and six months following the injection. Results: The majority (58.3%) of patients were male, while (41.7%) were female. At one month, a highly significant decrease occurred in VAS and ODI in the lidocaine and ozone groups compared to the botulinum toxin group (p < 0.001). At six months, there was a highly significant decrease in VAS and ODI in the botulinum toxin group compared to the lidocaine and ozone groups (p < 0.001). Conclusion: Botulinum toxin may assist in the medium- and long-term management of piriformis syndrome, while lidocaine injection and ozone therapy may help short-term treatment in patients not responding to conservative treatment and physiotherapy.

Evaluation of Interfascial Plane and Pericapsular Nerve Blocks to the Shoulder Joint: A Preliminary Analysis of Shoulder Anterior Capsular Block.

INTRODUCTION: The aim of this study is to verify if the shoulder anterior capsular block (SHAC), combined with other nerve blocks, is effective in relieving shoulder pain, avoiding motor block and allowing an early rehabilitation program. METHODS: Seventy-five consecutive patients with painful shoulder were treated with the SHAC, alone (30 patients) or in combination with a suprascapular nerve block (SSnb: 25 patients) or with pectoralis and serratus plane block (PECS-2: 20 patients). All blocks were performed with 0.2% ropivacaine plus 8 mg dexamethasone. All patients were treated with three-weekly physiotherapy sessions for the following 2 weeks and then with home exercises. RESULTS: The post-procedural analgesic effect was strong in all groups, with a mean change in numeric rating scale (NRS) values of -6.05 in group 1, -6.25 in group 2, and -6.19 in group 3 (p < .0001), allowing all patients to complete an immediate physiotherapy session. Only a few patients needed to repeat the procedure 1 week after the first treatment for the recurrence of pain. From the treatment to the end of the follow-up, we noted a further drop in mean pain NRS values of 1.90 in group 1 and 1.80 in groups 2 and 3. No difference in effect over time was observed among the different groups. No adverse event or motor block was recorded. CONCLUSION: This study demonstrates that the SHAC, alone or in combination with other peripheral nerve blocks, is an attractive alternative for shoulder pain management, especially when physiotherapy is required to recover shoulder function.

Anterior scalene plane block at the superior trunk level relieves referred shoulder pain after liver radiofrequency ablation: a technical report.

We report the first case of using an anterior scalene plane block at the superior trunk level achieving phrenic nerve blockade to treat intolerable referred shoulder pain after liver Radiofrequency Ablation (RFA) of a diaphragm-abutting liver tumor despite prevention with a full-dose non-steroidal anti-inflammatory drug. The anterior scalene plane block rapidly alleviated pain without significant complications.